Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT01117623
Collaborator
(none)
86
5
8
81
17.2
0.2
Study Details
Study Description
Brief Summary
Continuous dosing of BAY73-4506 in patients with advanced cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
86 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Official Title:
Open Label, Phase I Study to Determine the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetics, and Biomarker Status of BAY73-4506 in Patients With Advanced Malignancies
Study Start Date
:
Feb 1, 2007
Actual Primary Completion Date
:
Nov 1, 2013
Actual Study Completion Date
:
Nov 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1
|
Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg
Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral co-precipitate (CP) tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 2
|
Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg
Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 3
|
Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg
Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 4
|
Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg
Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 5
|
Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg
Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 6
|
Drug: HCC Child-Pugh A expansion cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 7
|
Drug: HCC Child-Pugh B expansion cohort: Regorafenib 100 mg
Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
| Experimental: Arm 8
|
Drug: NSCLC expansion cohort: Regorafenib 100 mg
Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) [Within first 4 weeks of treatment]
The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT).
- Maximum Observed Plasma Concentration After Single Dose Administration (Cmax) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose]
Cmax refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
- Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose]
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
- Cmax at Steady State During a Dosing Interval (Cmax,ss) [Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.]
Cmax,ss refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
- AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss) [Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.]
AUC(0-24),ss is a measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.
Secondary Outcome Measures
- AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast)) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose]
The AUC(0-tlast) is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
- Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose]
The AUC/D is a measure of systemic drug exposure (AUC) after the first single dose, which is then divided by that dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose]
Cmax/D refers to the highest measured drug concentration after a single dose administration, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.]
Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Half-life Associated With the Terminal Slope (T1/2) [Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.]
T1/2 is the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D) [Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
Cmax,ss/D refers to the highest measured drug concentration after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D) [Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
AUC(0-24)ss/D is a measure of systemic drug exposure (AUC) over 24 hours after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) [Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
Tmax,ss refers to the time after multiple dose administration and after a steady state concentration has been reached when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Ratio of Cmax,ss/Cmax (RACmax) [Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
RACmax is the ratio of the highest drug concentration at steady state to the highest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Ratio of Cmin,ss/Cmin (RACmin) [Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
RACmin is the ratio of the lowest drug concentration at steady state to the lowest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Ratio of AUCt,ss/AUCt (RAAUC) [Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
RAAUC is the ratio of the measure of systemic drug exposure over a specific dosing interval at steady state to the measure of systemic drug exposure over a specific dosing interval after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Ratio of AUCt,ss/AUC (RLIN) [Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose]
RLIN is the ratio of the measure of systemic drug exposure at steady state to the measure of systemic drug exposure after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
- Biomarker Vascular Endothelial Growth Factor (VEGF) Plasma Levels [No data obtained]
The analysis of Biomarker VEGF plasma levels is not done
- Biomarker Soluble Vascular Endothelial Growth Factor Receptor 2 (sCEGFR-2) Plasma Levels [No data obtained]
The analysis of Biomarker sCEGFR-2 plasma levels is not done.
Other Outcome Measures
- Tumor Progression in Dose Escalation Cohort [From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)]
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
- Tumor Progression in Expansion Cohort [From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)]
Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease.
- Tumor Response in Dose Escalation Cohort [From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)]
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
- Tumor Response in Expansion Cohort [From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)]
Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
18 years
-
Patients with advanced, histologically or cytologically confirmed solid tumors, malignant lymphomas, or multiple myeloma refractory to any standard therapy
-
Radiographical, hematological or clinically evaluable tumor
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
-
Life expectancy of at least 12 weeks
-
Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements:
-
Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
-
Signed informed consent must be obtained prior to any study specific procedures
Exclusion Criteria:
-
History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months or unstable angina or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
-
Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 90 mmHg, despite optimal medical management
-
History of HIV infection or chronic hepatitis B or C
-
Active clinically serious infections (> Grade 2 NCI Common Terminology Criteria for Adverse Events v3.0)
-
Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Patients with brain metastases must not be undergoing acute steroid therapy or steroid taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
-
Substance abuse, medical, psychological or social conditions that may interfere with the patient178s participation in the study or evaluation of the study results
-
Radiotherapy to the target lesions within 3 weeks prior to Day 1, Cycle 1 (first dose of study drug). (Palliative radiotherapy will be allowed). Radiotherapy to the target lesions during study will be regarded as progressive disease
-
Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis and T1] or any cancer curatively treated > 3 years prior to study entry.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Los Angeles | California | United States | 90095 | |
| 2 | Aurora | Colorado | United States | 80045 | |
| 3 | Houston | Texas | United States | 77030 | |
| 4 | San Antonio | Texas | United States | 78229-3307 | |
| 5 | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01117623
Other Study ID Numbers:
- 11651
First Posted:
May 5, 2010
Last Update Posted:
Nov 18, 2015
Last Verified:
Nov 1, 2015
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Adult participants with advanced, histologically or cytologically confirmed solid tumors (including non-small-cell lung cancer (NSCLC) participants enrolled in the expansion portion of the study), malignant lymphomas, or multiple myeloma were enrolled in 5 centers in the USA from 01 FEB 2007 to 22 Apr 2011. |
|---|---|
| Pre-assignment Detail | 109 (73 male and 36 female) participants were screened according to the inclusion and exclusion criteria to determine their appropriateness for inclusion in the study, and 86 (54 male and 32 female) participants were included at 5 centers, valid for safety population, 81 participants valid for ITT efficacy analysis and PK population. |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral co-precipitate (CP) tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Period Title: Overall Study | ||||||||
| STARTED | 3 | 8 | 11 | 6 | 10 | 16 | 6 | 26 |
| ITT Efficacy Analysis Population | 3 | 8 | 11 | 5 | 10 | 16 | 6 | 22 |
| PK Population | 3 | 8 | 10 | 6 | 10 | 14 | 6 | 24 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 8 | 11 | 6 | 10 | 16 | 6 | 26 |
Baseline Characteristics
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Total of all reporting groups |
| Overall Participants | 3 | 8 | 11 | 6 | 10 | 16 | 6 | 26 | 86 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [Years] |
63.3
(8.1)
|
55.3
(13.1)
|
61.9
(8.8)
|
59.2
(10.7)
|
55.7
(13.7)
|
56.6
(13.2)
|
56.7
(13.1)
|
62.4
(12.2)
|
59.6
(11.8)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
0
0%
|
3
37.5%
|
4
36.4%
|
3
50%
|
7
70%
|
4
25%
|
2
33.3%
|
9
34.6%
|
32
37.2%
|
| Male |
3
100%
|
5
62.5%
|
7
63.6%
|
3
50%
|
3
30%
|
12
75%
|
4
66.7%
|
17
65.4%
|
54
62.8%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) |
|---|---|
| Description | The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT). |
| Time Frame | Within first 4 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population; dose escalation cohorts only |
| Arm/Group Title | Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg |
|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 37 |
| Number [mg] |
100
|
| Title | Maximum Observed Plasma Concentration After Single Dose Administration (Cmax) |
|---|---|
| Description | Cmax refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Cmax in at least one analyte was 1 (M5) in 20mg; 7 (regorafenib and M2) and 5 (M5) in 40mg; 13 (M5) in HCC Child-Pugh A; 22 (M5) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,7,10,6,10,14,4,24) |
0.330
(14.8)
|
0.422
(27.4)
|
1.25
(30.7)
|
1.87
(24.0)
|
1.90
(51.2)
|
1.38
(98)
|
1.42
(76)
|
1.25
(68.5)
|
| M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24) |
0.0181
(244)
|
0.0867
(110)
|
0.401
(51.2)
|
0.645
(43.2)
|
0.606
(97.2)
|
0.42
(154)
|
0.54
(129)
|
0.388
(190)
|
| M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22) |
0.00290
(NA)
|
0.00738
(124)
|
0.0299
(118)
|
0.0459
(59.2)
|
0.0500
(140)
|
0.036
(110)
|
0.035
(352)
|
0.321
(142)
|
| Title | Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC) |
|---|---|
| Description | The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population; Number of Participants with at least one evaluable AUC were 5 (regorafenib) and 6 (M2) in 40mg; 5 (regorafenib and M2) in 100 mg; 3 (M2) in 120 mg; 6 (regorafenib and M2) in 140 mg; 9 (regorafenib), 10 (M2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M2) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,5,5,6,6,9,3,19) |
NA
(NA)
|
16.3
(76.3)
|
43.7
(34.9)
|
52.9
(64.6)
|
52.5
(66.4)
|
45.2
(84.3)
|
57.7
(30.9)
|
33.5
(43.9)
|
| M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16) |
NA
(NA)
|
3.53
(161)
|
12.8
(37.0)
|
21.0
(71.5)
|
19.5
(20.3)
|
15.3
(69.9)
|
27.2
(74.6)
|
11.6
(77.8)
|
| M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
15.8
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Title | Cmax at Steady State During a Dosing Interval (Cmax,ss) |
|---|---|
| Description | Cmax,ss refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached. |
| Time Frame | Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,6,6,2,3,0,1,5) |
1.27
(19.4)
|
1.50
(37.0)
|
4.27
(22.9)
|
3.62
(5.77)
|
5.37
(30.9)
|
NA
(NA)
|
2.69
(NA)
|
2.55
(92.4)
|
| M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5) |
0.0912
(39.5)
|
0.520
(74.3)
|
2.48
(36.3)
|
2.97
(217)
|
2.20
(106)
|
NA
(NA)
|
2.40
(NA)
|
0.911
(126)
|
| M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5) |
0.00911
(15.7)
|
0.174
(151)
|
1.38
(87.0)
|
3.29
(1400)
|
0.948
(343)
|
NA
(NA)
|
1.59
(NA)
|
0.349
(153)
|
| Title | AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss) |
|---|---|
| Description | AUC(0-24),ss is a measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached. |
| Time Frame | Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable AUC(0-24),ss in at least one analyte in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,6,6,2,3,0,1,5) |
12.9
(21.2)
|
18.1
(35.9)
|
49.6
(18.5)
|
40.6
(32.9)
|
60.4
(18.5)
|
NA
(NA)
|
39.2
(NA)
|
35.8
(83.9)
|
| M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5) |
1.11
(42.9)
|
7.20
(56.7)
|
31.5
(25.2)
|
40.9
(245)
|
29.7
(88.8)
|
NA
(NA)
|
46.8
(NA)
|
14.6
(104)
|
| M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5) |
0.122
(18.7)
|
2.22
(136)
|
18.6
(58.1)
|
44.4
(3050)
|
12.9
(231)
|
NA
(NA)
|
34.3
(NA)
|
6.17
(133)
|
| Title | AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast)) |
|---|---|
| Description | The AUC(0-tlast) is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable AUC(0-tlast) in at least one analyte were 1(M-5) in 20mg; 7 (regorafenib and M-2) and 5 (M-5) in 40mg; 13 (M-5) in HCC Child Pugh A; 22 (M5) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,7,10,6,10,14,4,24) |
7.98
(28.0)
|
9.12
(38.8)
|
32.7
(37.9)
|
33.5
(60.4)
|
35.8
(57.0)
|
26.8
(67.5)
|
33.0
(112)
|
18.7
(55.3)
|
| M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24) |
0.384
(330)
|
2.02
(108)
|
11.3
(47.4)
|
14.2
(53.4)
|
13.6
(82.6)
|
8.84
(122)
|
13.4
(194)
|
6.54
(156)
|
| M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22) |
0.0275
(NA)
|
0.165
(254)
|
0.976
(111)
|
1.51
(71.1)
|
1.54
(71.1)
|
1.02
(122)
|
0.821
(587)
|
0.821
(254)
|
| Title | Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D) |
|---|---|
| Description | The AUC/D is a measure of systemic drug exposure (AUC) after the first single dose, which is then divided by that dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population; Number of Participants with at least one evaluable AUC/D were 5 (regorafenib) and 6 (M-2) in 40mg; 5 (regorafenib and M-2) in 100 mg; 3 (M-2) in 120 mg; 6 (regorafenib and M-2) in 140 mg; 9 (regorafenib), 10 (M-2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M-2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M-2) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,5,5,6,6,9,3,19) |
NA
(NA)
|
0.407
(76.3)
|
0.437
(34.9)
|
0.441
(64.6)
|
0.375
(66.4)
|
0.452
(84.3)
|
0.577
(30.9)
|
0.355
(43.9)
|
| M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16) |
NA
(NA)
|
0.0855
(161)
|
0.124
(37.0)
|
0.169
(71.5)
|
0.135
(20.3)
|
0.148
(69.9)
|
0.263
(74.6)
|
0.113
(77.8)
|
| M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
0.0157
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Title | Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D) |
|---|---|
| Description | Cmax/D refers to the highest measured drug concentration after a single dose administration, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Cmax/D in at least one analyte was 1 (M5) in 20mg; 7 (regorafenib and M2) and 5 (M5) in 40mg; 13 (M5) in HCC Child-Pugh A; 22 (M5) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,7,10,6,10,14,4,24) |
0.0165
(14.8)
|
0.0106
(27.4)
|
0.0125
(30.7)
|
0.0156
(24.0)
|
0.0136
(51.2)
|
0.0138
(97.9)
|
0.0142
(76.1)
|
0.0125
(68.5)
|
| M2 (BAY75-7495) (n=3,7,10,6,10,14,4,24) |
0.000874
(244)
|
0.00210
(110)
|
0.00388
(51.2)
|
0.00520
(43.2)
|
0.00419
(97.2)
|
0.00404
(154)
|
0.00526
(129)
|
0.00376
(190)
|
| M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22) |
0.000114
(NA)
|
0.000184
(124)
|
0.000298
(118)
|
0.000381
(59.2)
|
0.000355
(140)
|
0.000355
(110)
|
0.000351
(352)
|
0.000320
(142)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
|---|---|
| Description | Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Tmax in at least one analyte were 1 (M-5) in 20 mg; 5 (M-5) in 40mg; 13 (M-5) in HCC Child Pugh A; 22 (M-5) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,8,10,6,10,14,4,24) |
8.00
|
2.02
|
5.00
|
6.00
|
3.01
|
3.03
|
3.00
|
2.00
|
| M2 (BAY75-7495) (n=3,8,10,6,10,14,4,24) |
8.00
|
2.02
|
10.0
|
9.00
|
4.00
|
3.01
|
10.0
|
2.01
|
| M5 (BAY81-8752) (n=1,5,10,6,10,13,4,22) |
48.0
|
47.8
|
48.0
|
24.6
|
47.6
|
46.8
|
34.9
|
47.8
|
| Title | Half-life Associated With the Terminal Slope (T1/2) |
|---|---|
| Description | T1/2 is the period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population; Number of Patients with at least an evaluable T1/2 were 5 (regorafenib) and 6 (M2) in 40mg; 5 (regorafenib and M2) in 100 mg; 3 (regorafenib and M2) in 120 mg; 6 (regorafenib and M2) in 140 mg; 9 (regorafenib), 10(M2) and 1 (M5) in HCC Child Pugh A; 3 (regorafenib) and 2 (M2) in HCC Child Pugh B; 19 (regorafenib) and 16 (M2) in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,5,5,3,6,9,22,19) |
NA
(NA)
|
41.6
(41.1)
|
31.6
(32.5)
|
27.7
(47.8)
|
23.2
(43.6)
|
25.2
(52.0)
|
745.3
(79.7)
|
33.3
(64.8)
|
| M2 (BAY75-7495) (n=3,6,5,3,6,10,2,16) |
NA
(NA)
|
40.3
(52.3)
|
24.8
(28.6)
|
22.9
(27.6)
|
22.7
(64.7)
|
24.0
(56.3)
|
19.2
(16.4)
|
26.4
(73.4)
|
| M5 (BAY81-8752) (n=3,8,10,6,10,1,4,24) |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
68.7
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Title | Cmax at Steady State During a Dosing Interval Divided by Dose (Cmax,ss/D) |
|---|---|
| Description | Cmax,ss/D refers to the highest measured drug concentration after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss/D in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,6,6,2,3,0,1,5) |
0.0636
(19.4)
|
0.0374
(37.0)
|
0.0427
(22.9)
|
0.0302
(5.77)
|
0.0383
(30.9)
|
NA
(NA)
|
0.0269
(NA)
|
0.0255
(92.4)
|
| M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5) |
0.00441
(39.5)
|
0.0126
(74.3)
|
0.0241
(36.3)
|
0.0240
(217)
|
0.0152
(106)
|
NA
(NA)
|
0.0232
(NA)
|
0.00881
(126)
|
| M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5) |
0.000454
(15.7)
|
0.00434
(151)
|
0.0137
(87.9)
|
0.0273
(1400)
|
0.00674
(343)
|
NA
(NA)
|
0.0159
(NA)
|
0.00347
(153)
|
| Title | AUC From Time 0 to 24 Hours at Steady State Divided by Dose (AUC(0-24)ss/D) |
|---|---|
| Description | AUC(0-24)ss/D is a measure of systemic drug exposure (AUC) over 24 hours after multiple dose administration and after a steady state concentration has been reached, which is then divided by the administered dose. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable AUC(0-24)ss/D in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,6,6,2,3,0,1,5) |
0.644
(21.2)
|
0.452
(35.9)
|
0.496
(18.5)
|
0.338
(32.9)
|
0.431
(18.5)
|
NA
(NA)
|
0.392
(NA)
|
0.358
(83.8)
|
| M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5) |
0.0538
(42.9)
|
0.174
(56.7)
|
0.305
(25.2)
|
0.330
(245)
|
0.205
(88.8)
|
NA
(NA)
|
0.453
(NA)
|
0.141
(104)
|
| M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5) |
0.00609
(18.7)
|
0.0552
(136)
|
0.185
(58.1)
|
0.368
(3050)
|
0.0916
(231)
|
NA
(NA)
|
0.342
(NA)
|
0.0615
(133)
|
| Title | Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) |
|---|---|
| Description | Tmax,ss refers to the time after multiple dose administration and after a steady state concentration has been reached when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Tmax,ss in at least one analyte were 6 in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,6,6,2,3,0,1,5) |
2.00
|
2.00
|
1.25
|
2.00
|
2.00
|
NA
|
4.03
|
4.00
|
| M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5) |
2.00
|
1.50
|
2.00
|
2.00
|
2.00
|
NA
|
10.0
|
4.00
|
| M5 (BAY81-8752) (n=3,6,6,2,3,0,1,5) |
2.00
|
1.00
|
1.00
|
1.50
|
1.00
|
NA
|
0.00
|
4.00
|
| Title | Ratio of Cmax,ss/Cmax (RACmax) |
|---|---|
| Description | RACmax is the ratio of the highest drug concentration at steady state to the highest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Cmax,ss and Cmax in at least one analyte were 1 (M5) in 20mg; 5 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,5,6,2,3,0,1,5) |
3.78
|
3.34
|
3.50
|
1.53
|
2.84
|
NA
|
1.90
|
1.82
|
| M2 (BAY75-7495) (n=3,5,6,2,3,0,1,5) |
4.86
|
4.26
|
5.39
|
3.06
|
3.33
|
NA
|
3.40
|
1.83
|
| M5 (BAY81-8752) (n=1,4,6,2,3,0,1,5) |
3.80
|
22.8
|
32.5
|
39.3
|
18.9
|
NA
|
45.0
|
11.9
|
| Title | Ratio of Cmin,ss/Cmin (RACmin) |
|---|---|
| Description | RACmin is the ratio of the lowest drug concentration at steady state to the lowest drug concentration after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable Cmin,ss and Cmin in at least one analyte were 0 (M5) in 20mg; 6 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,6,6,2,3,0,1,5) |
4.82
|
34.9
|
26.1
|
413
|
10.9
|
NA
|
7.80
|
14.1
|
| M2 (BAY75-7495) (n=3,6,6,2,3,0,1,5) |
4.81
|
10.4
|
24.2
|
12.6
|
3.33
|
NA
|
103
|
11.5
|
| M5 (BAY81-8752) (n=0,4,,6,2,3,0,1,5) |
NA
|
26.1
|
102
|
335
|
46.2
|
NA
|
257
|
22.4
|
| Title | Ratio of AUCt,ss/AUCt (RAAUC) |
|---|---|
| Description | RAAUC is the ratio of the measure of systemic drug exposure over a specific dosing interval at steady state to the measure of systemic drug exposure over a specific dosing interval after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic population; Number of Participants with an evaluable AUCt,ss and AUCt in at least one analyte were 0 (M5) in 20mg; 5 (regorafenib and M2) and 4 (M5) in 40mg; 6 in 100 mg; 2 in 120 mg; 3 in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 5 in NSCLC |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=3,5,6,2,3,0,1,5) |
3.20
|
3.78
|
3.15
|
1.37
|
3.61
|
NA
|
2.10
|
2.67
|
| M2 (BAY75-7495) (n=3,5,6,2,3,0,1,5) |
5.79
|
4.72
|
4.63
|
2.71
|
3.60
|
NA
|
4.60
|
2.74
|
| M5 (BAY81-8752) (n=0,4,,6,2,3,0,1,5) |
NA
|
28.1
|
41.2
|
34.7
|
23.9
|
NA
|
63.0
|
18.5
|
| Title | Ratio of AUCt,ss/AUC (RLIN) |
|---|---|
| Description | RLIN is the ratio of the measure of systemic drug exposure at steady state to the measure of systemic drug exposure after single dose administration. It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Blood samples were collected on Cycle 1, Day 1 and Cycle 2, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK population; Number of Participants with an evaluable AUCt,ss and AUC in at least one analyte were 0 in 20mg; 3 (regorafenib) and 4 (M2) in 40mg; 3 in 100 mg; 2 (regorafenib) and 0 (M2) in 120 mg; 3 (regorafenib) and 2 (M2) in 140 mg; 0 in HCC Child Pugh A; 1 in HCC Child Pugh B; 4 in NSCLC; No participants have evaluable data for M5. |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg | HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh A status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Hepatocellular carcinoma (HCC) Participants with Child Pugh B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 10 | 6 | 10 | 14 | 4 | 24 |
| Regorafenib (n=0,3,3,2,3,0,1,4) |
NA
|
1.53
|
1.27
|
0.600
|
2.20
|
NA
|
0.800
|
1.11
|
| M2 (BAY75-7495) (n=0,4,3,0,2,0,1,4) |
NA
|
1.63
|
2.13
|
NA
|
1.39
|
NA
|
2.70
|
1.27
|
| M5 (BAY81-8752) (n=0) |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
| Title | Biomarker Vascular Endothelial Growth Factor (VEGF) Plasma Levels |
|---|---|
| Description | The analysis of Biomarker VEGF plasma levels is not done |
| Time Frame | No data obtained |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg |
|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 0 |
| Title | Biomarker Soluble Vascular Endothelial Growth Factor Receptor 2 (sCEGFR-2) Plasma Levels |
|---|---|
| Description | The analysis of Biomarker sCEGFR-2 plasma levels is not done. |
| Time Frame | No data obtained |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Regorafenib, 20 mg, 40 mg, 100 mg, 120 mg, 140 mg |
|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg, 40 mg, 100 mg, 120 mg, 140 mg oral CP tablet of regorafenib respectively on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 0 |
| Title | Tumor Progression in Dose Escalation Cohort |
|---|---|
| Description | Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease. |
| Time Frame | From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) efficacy analysis (set) |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 11 | 5 | 10 |
| Participants without progression |
1
33.3%
|
3
37.5%
|
9
81.8%
|
2
33.3%
|
5
50%
|
| Participants with progression |
2
66.7%
|
5
62.5%
|
2
18.2%
|
3
50%
|
5
50%
|
| Title | Tumor Progression in Expansion Cohort |
|---|---|
| Description | Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Tumor progression evaluates changes in a tumor or tumors over time due to worsening of disease. Measurements and observations of the tumor status were performed before, during and after treatment. Progression for solid tumors was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) criteria. Tumor dimensions were measured in millimeters and the longest diameter (LD) was recorded for up to 5 lesions per organ and 10 lesions total. A sum of the LD for all target lesions was recorded. The use of a 20% increase in the sum of LD of target lesions from the smallest sum or appearance of a new lesion was assessed as progression of disease. |
| Time Frame | From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT efficacy analysis (set), expansion cohorts only |
| Arm/Group Title | HCC Expansion Cohort: Regorafenib 100 mg | NSCLC Expansion Cohort: Regorafenib 100 mg |
|---|---|---|
| Arm/Group Description | Hepatocellular carcinoma (HCC) Participants with Child Pugh A or B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 22 | 22 |
| Participants without progression |
10
333.3%
|
6
75%
|
| Participants with progression |
12
400%
|
16
200%
|
| Title | Tumor Response in Dose Escalation Cohort |
|---|---|
| Description | Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes. |
| Time Frame | From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT efficacy analysis (set) |
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 3 | 8 | 11 | 5 | 10 |
| Not assessable |
0
0%
|
1
12.5%
|
2
18.2%
|
0
0%
|
0
0%
|
| Partial Response (PR) |
0
0%
|
0
0%
|
2
18.2%
|
0
0%
|
1
10%
|
| Stable Disease (SD) |
1
33.3%
|
2
25%
|
5
45.5%
|
2
33.3%
|
4
40%
|
| Progressive Disease (PD) |
2
66.7%
|
4
50%
|
2
18.2%
|
2
33.3%
|
4
40%
|
| Progression |
0
0%
|
1
12.5%
|
0
0%
|
1
16.7%
|
1
10%
|
| Title | Tumor Response in Expansion Cohort |
|---|---|
| Description | Tumor Response (= Best Overall Response) of a participant was defined as the best tumor response (Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes. |
| Time Frame | From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT efficacy analysis (set), expansion cohorts only |
| Arm/Group Title | HCC Expansion Cohort, Regorafenib 100 mg | NSCLC Expansion Cohort, Regorafenib 100 mg |
|---|---|---|
| Arm/Group Description | Hepatocellular carcinoma (HCC) Participants with Child Pugh A or B status in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. |
| Measure Participants | 22 | 22 |
| Not assessable |
3
100%
|
1
12.5%
|
| Partial Response (PR) |
1
33.3%
|
0
0%
|
| Stable Disease (SD) |
6
200%
|
5
62.5%
|
| Progressive Disease (PD) |
10
333.3%
|
12
150%
|
| Progression |
2
66.7%
|
4
50%
|
Adverse Events
| Time Frame | Adverse events were collected after signing the informed consent of the first participant until the end of study completion for the last patient, therefore for the study over a period of approximately 6 years and 9 months | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | |||||
| Arm/Group Description | Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. This arm includes the participants from the dose escalation cohort: Regorafenib 100 mg and the three Expansion Cohorts 'HCC Child-Pugh A Expansion Cohort: Regorafenib 100 mg', 'HCC Child-Pugh B Expansion Cohort: Regorafenib 100 mg', 'NSCLC Expansion Cohort: Regorafenib 100 mg'. | Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle. | |||||
All Cause Mortality |
||||||||||
| Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 3/8 (37.5%) | 31/59 (52.5%) | 3/6 (50%) | 6/10 (60%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Edema: Limb | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Cardiac disorders | ||||||||||
| Cardiac General - Other | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 2/10 (20%) | |||||
| Conduction abnormality, AV Block - 3rd Degree (Complete AV Block) | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hypertension | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Hypotension | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Pericardial effusion | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pericarditis | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| SupraVentricular arrhythmia, Sinus tachycardia | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Eye disorders | ||||||||||
| Blurred vision | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Ocular - Other | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Constipation | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Dehydration | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| GI - Other | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Nausea | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Obstruction, GI, Duodenum | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Obstruction, GI, Small bowel NOS | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| General disorders | ||||||||||
| Constitutional Symptoms - Other | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Death not associated with CTCAE term, Disease Progression NOS | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 0/6 (0%) | 0/10 (0%) | |||||
| Fatigue | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Fever | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Pain, Abdomen NOS | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Back | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Chest wall | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Chest/thorax NOS | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pain, Joint | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Other (Specify) | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Liver dysfunction | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pancreatitis | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infections and infestations | ||||||||||
| Infection (Documented clinically), Appendix | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Bladder (urinary) | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection (Documented clinically), Blood | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Bronchus | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Lung (pneumonia) | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Urinary tract NOS | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection - Other | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection with normal ANC, Colon | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Bilirubin (hyperbilirubinemia) | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hyperuricemia | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Hyponatremia | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Fracture | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Secondary Malignancy (possibly related to cancer treatment) | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Nervous system disorders | ||||||||||
| Neurology - Other | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Neuropathy: motor | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Renal - Other | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Renal failure | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnea (shortness of breath) | 0/3 (0%) | 1/8 (12.5%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pleural effusion | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pneumothorax | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pulmonary - Other | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Vascular disorders | ||||||||||
| CNS hemorrhage | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hemorrhage pulmonary, Respiratory tract NOS | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Thrombosis/thrombus/embolism | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg | Regorafenib (Stivarga, BAY73-4506) 100 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg | Escalation Cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 8/8 (100%) | 58/59 (98.3%) | 5/6 (83.3%) | 10/10 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Blood - Other | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Edema: Limb | 0/3 (0%) | 1/8 (12.5%) | 11/59 (18.6%) | 2/6 (33.3%) | 3/10 (30%) | |||||
| Hemoglobin | 0/3 (0%) | 1/8 (12.5%) | 5/59 (8.5%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Leukocytes | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Lymphatics - Other | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Neutrophils | 0/3 (0%) | 1/8 (12.5%) | 1/59 (1.7%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Platelets | 0/3 (0%) | 1/8 (12.5%) | 9/59 (15.3%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Cardiac disorders | ||||||||||
| Cardiac General - Other | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Hypertension | 0/3 (0%) | 0/8 (0%) | 21/59 (35.6%) | 2/6 (33.3%) | 2/10 (20%) | |||||
| Hypotension | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 2/6 (33.3%) | 1/10 (10%) | |||||
| Left ventricular systolic dysfunction | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Palpitations | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| SupraVentricular arrhythmia, Atrial fibrillation | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| SupraVentricular arrhythmia, Sinus bradycardia | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| SupraVentricular arrhythmia, Sinus tachycardia | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 3/10 (30%) | |||||
| Ventricular arrhythmia, Ventricular tachycardia | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Auditory/Ear - Other | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Hearing (without monitoring program) | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Otitis, external | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Tinnitus | 0/3 (0%) | 1/8 (12.5%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Endocrine disorders | ||||||||||
| Hot flashes | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Hypothyroidism | 0/3 (0%) | 1/8 (12.5%) | 13/59 (22%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Eye disorders | ||||||||||
| Blurred vision | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Diplopia | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Gastrointestinal disorders | ||||||||||
| Anorexia | 0/3 (0%) | 0/8 (0%) | 22/59 (37.3%) | 2/6 (33.3%) | 2/10 (20%) | |||||
| Constipation | 0/3 (0%) | 2/8 (25%) | 14/59 (23.7%) | 3/6 (50%) | 3/10 (30%) | |||||
| Dehydration | 0/3 (0%) | 0/8 (0%) | 7/59 (11.9%) | 0/6 (0%) | 0/10 (0%) | |||||
| Diarrhea | 2/3 (66.7%) | 2/8 (25%) | 15/59 (25.4%) | 2/6 (33.3%) | 4/10 (40%) | |||||
| Distension | 0/3 (0%) | 1/8 (12.5%) | 3/59 (5.1%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Dry mouth | 0/3 (0%) | 0/8 (0%) | 8/59 (13.6%) | 0/6 (0%) | 2/10 (20%) | |||||
| Dysphagia | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 2/6 (33.3%) | 1/10 (10%) | |||||
| Flatulence | 1/3 (33.3%) | 1/8 (12.5%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| GI - Other | 0/3 (0%) | 2/8 (25%) | 3/59 (5.1%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Heartburn | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Hemorrhoids | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Mucositis (clinical exam), Oral cavity | 0/3 (0%) | 2/8 (25%) | 5/59 (8.5%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Mucositis (functional/symptomatic), Oral cavity | 0/3 (0%) | 0/8 (0%) | 11/59 (18.6%) | 3/6 (50%) | 4/10 (40%) | |||||
| Nausea | 1/3 (33.3%) | 2/8 (25%) | 17/59 (28.8%) | 2/6 (33.3%) | 3/10 (30%) | |||||
| Taste Alteration | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 2/6 (33.3%) | 1/10 (10%) | |||||
| Vomiting | 1/3 (33.3%) | 1/8 (12.5%) | 13/59 (22%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| General disorders | ||||||||||
| Constitutional Symptoms - Other | 1/3 (33.3%) | 1/8 (12.5%) | 2/59 (3.4%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Fatigue | 2/3 (66.7%) | 5/8 (62.5%) | 28/59 (47.5%) | 4/6 (66.7%) | 5/10 (50%) | |||||
| Fever | 0/3 (0%) | 0/8 (0%) | 9/59 (15.3%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Insomnia | 0/3 (0%) | 1/8 (12.5%) | 11/59 (18.6%) | 0/6 (0%) | 4/10 (40%) | |||||
| Pain, Abdomen NOS | 1/3 (33.3%) | 2/8 (25%) | 9/59 (15.3%) | 2/6 (33.3%) | 3/10 (30%) | |||||
| Pain, Anus | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pain, Back | 0/3 (0%) | 1/8 (12.5%) | 13/59 (22%) | 4/6 (66.7%) | 2/10 (20%) | |||||
| Pain, Bladder | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pain, Buttock | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Chest wall | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Pain, Chest/thorax NOS | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pain, Dental/teeth/peridontal | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Pain, Extremity - limb | 0/3 (0%) | 0/8 (0%) | 15/59 (25.4%) | 5/6 (83.3%) | 5/10 (50%) | |||||
| Pain, Head/headache | 0/3 (0%) | 1/8 (12.5%) | 8/59 (13.6%) | 2/6 (33.3%) | 1/10 (10%) | |||||
| Pain, Joint | 0/3 (0%) | 1/8 (12.5%) | 6/59 (10.2%) | 2/6 (33.3%) | 1/10 (10%) | |||||
| Pain, Muscle | 0/3 (0%) | 0/8 (0%) | 10/59 (16.9%) | 4/6 (66.7%) | 3/10 (30%) | |||||
| Pain, Neuralgia/peripheral nerve | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pain, Oral cavity | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Pain, Other (Specify) | 1/3 (33.3%) | 1/8 (12.5%) | 4/59 (6.8%) | 1/6 (16.7%) | 3/10 (30%) | |||||
| Pain, Pain NOS | 0/3 (0%) | 0/8 (0%) | 7/59 (11.9%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Scalp | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pain, Throat/pharynx/larynx | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pain, Tumor pain | 0/3 (0%) | 2/8 (25%) | 1/59 (1.7%) | 0/6 (0%) | 2/10 (20%) | |||||
| Rigors/chills | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Sweating | 0/3 (0%) | 1/8 (12.5%) | 6/59 (10.2%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Syndromes - Other | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Weight loss | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Immune system disorders | ||||||||||
| Allergic reaction | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Allergy - Other | 0/3 (0%) | 1/8 (12.5%) | 1/59 (1.7%) | 0/6 (0%) | 2/10 (20%) | |||||
| Rhinitis | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infections and infestations | ||||||||||
| Infection (Documented clinically), Abdomen NOS | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Bladder (urinary) | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Bronchus | 0/3 (0%) | 1/8 (12.5%) | 4/59 (6.8%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Conjunctiva | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection (Documented clinically), Lip/perioral | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection (Documented clinically), Neck NOS | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection (Documented clinically), Pharynx | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection (Documented clinically), Upper airway NOS | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection (Documented clinically), Urinary tract NOS | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Infection - Other | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection with normal ANC, Anal/perianal | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Infection with normal ANC, Pharynx | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Infection with normal ANC, Sinus | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Infection with normal ANC, Upper airway NOS | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| ALT | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 0/6 (0%) | 1/10 (10%) | |||||
| AST | 0/3 (0%) | 0/8 (0%) | 7/59 (11.9%) | 0/6 (0%) | 2/10 (20%) | |||||
| Bilirubin (hyperbilirubinemia) | 0/3 (0%) | 0/8 (0%) | 7/59 (11.9%) | 0/6 (0%) | 5/10 (50%) | |||||
| CPK | 0/3 (0%) | 1/8 (12.5%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Cholesterol (serum-high hypercholesteremia) | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Creatinine | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Hyperglycemia | 0/3 (0%) | 1/8 (12.5%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hyperuricemia | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 0/6 (0%) | 1/10 (10%) | |||||
| Hypocalcemia | 0/3 (0%) | 1/8 (12.5%) | 4/59 (6.8%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hypoglycemia | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Hypokalemia | 0/3 (0%) | 2/8 (25%) | 6/59 (10.2%) | 0/6 (0%) | 3/10 (30%) | |||||
| Hypomagnesemia | 1/3 (33.3%) | 0/8 (0%) | 8/59 (13.6%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Hyponatremia | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 0/6 (0%) | 1/10 (10%) | |||||
| Hypophosphatemia | 0/3 (0%) | 0/8 (0%) | 10/59 (16.9%) | 2/6 (33.3%) | 2/10 (20%) | |||||
| Lipase | 1/3 (33.3%) | 0/8 (0%) | 3/59 (5.1%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Metabolic/Lab - Other | 0/3 (0%) | 1/8 (12.5%) | 5/59 (8.5%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Proteinuria | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 0/6 (0%) | 1/10 (10%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Fracture | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Gait/walking | 0/3 (0%) | 0/8 (0%) | 6/59 (10.2%) | 2/6 (33.3%) | 0/10 (0%) | |||||
| Muscle weakness left-sided | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Muscle weakness, Extremity - lower | 0/3 (0%) | 0/8 (0%) | 4/59 (6.8%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Musculoskeletal - Other | 0/3 (0%) | 3/8 (37.5%) | 9/59 (15.3%) | 0/6 (0%) | 0/10 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Secondary Malignancy (possibly related to cancer treatment) | 1/3 (33.3%) | 1/8 (12.5%) | 1/59 (1.7%) | 0/6 (0%) | 0/10 (0%) | |||||
| Nervous system disorders | ||||||||||
| CNS ischemia | 0/3 (0%) | 1/8 (12.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Confusion | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Dizziness | 0/3 (0%) | 1/8 (12.5%) | 6/59 (10.2%) | 2/6 (33.3%) | 1/10 (10%) | |||||
| Memory impairment | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Mood Alteration, Agitation | 1/3 (33.3%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Mood Alteration, Anxiety | 0/3 (0%) | 0/8 (0%) | 5/59 (8.5%) | 2/6 (33.3%) | 3/10 (30%) | |||||
| Mood Alteration, Depression | 1/3 (33.3%) | 1/8 (12.5%) | 1/59 (1.7%) | 0/6 (0%) | 1/10 (10%) | |||||
| Neurology - Other | 0/3 (0%) | 1/8 (12.5%) | 3/59 (5.1%) | 0/6 (0%) | 1/10 (10%) | |||||
| Neuropathy: Cranial, CN VII Motor-face; Sensory-taste | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Neuropathy: Cranial, CN XI Motor-Sternomastoid And Trapezius | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Neuropathy: Cranial, CN XII Motor-tongue | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Neuropathy: motor | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Neuropathy: sensory | 0/3 (0%) | 2/8 (25%) | 13/59 (22%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Somnolence | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Incontinence, urinary | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Renal - Other | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Urinary frequency | 0/3 (0%) | 0/8 (0%) | 2/59 (3.4%) | 0/6 (0%) | 1/10 (10%) | |||||
| Urinary retention | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 1/10 (10%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Erectile dysfunction | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Gynecomastia | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 0/3 (0%) | 0/8 (0%) | 18/59 (30.5%) | 0/6 (0%) | 0/10 (0%) | |||||
| Dyspnea (shortness of breath) | 0/3 (0%) | 0/8 (0%) | 14/59 (23.7%) | 2/6 (33.3%) | 2/10 (20%) | |||||
| Hypoxia | 0/3 (0%) | 0/8 (0%) | 1/59 (1.7%) | 1/6 (16.7%) | 0/10 (0%) | |||||
| Pulmonary - Other | 0/3 (0%) | 1/8 (12.5%) | 9/59 (15.3%) | 2/6 (33.3%) | 2/10 (20%) | |||||
| Voice changes | 1/3 (33.3%) | 2/8 (25%) | 13/59 (22%) | 0/6 (0%) | 2/10 (20%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Acne | 0/3 (0%) | 3/8 (37.5%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Alopecia | 1/3 (33.3%) | 0/8 (0%) | 5/59 (8.5%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Bruising | 0/3 (0%) | 0/8 (0%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Burn | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Decubitus | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Dermatitis, Radiation | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Dermatology - Other | 1/3 (33.3%) | 2/8 (25%) | 10/59 (16.9%) | 0/6 (0%) | 1/10 (10%) | |||||
| Dry skin | 0/3 (0%) | 1/8 (12.5%) | 9/59 (15.3%) | 1/6 (16.7%) | 1/10 (10%) | |||||
| Flushing | 0/3 (0%) | 1/8 (12.5%) | 3/59 (5.1%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hand-foot skin reaction | 0/3 (0%) | 1/8 (12.5%) | 23/59 (39%) | 2/6 (33.3%) | 4/10 (40%) | |||||
| Hyperpigmentation | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Photosensitivity | 1/3 (33.3%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 0/10 (0%) | |||||
| Pruritus | 0/3 (0%) | 2/8 (25%) | 2/59 (3.4%) | 1/6 (16.7%) | 2/10 (20%) | |||||
| Rash/desquamation | 1/3 (33.3%) | 6/8 (75%) | 19/59 (32.2%) | 5/6 (83.3%) | 9/10 (90%) | |||||
| Vascular disorders | ||||||||||
| Hemorrhage pulmonary, Nose | 0/3 (0%) | 1/8 (12.5%) | 2/59 (3.4%) | 0/6 (0%) | 0/10 (0%) | |||||
| Hemorrhage, GI, Anus | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
| Vascular - Other | 0/3 (0%) | 0/8 (0%) | 0/59 (0%) | 0/6 (0%) | 1/10 (10%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | BAYER |
| Phone | |
| clinical-trials-contact@bayerhealthcare.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01117623
Other Study ID Numbers:
- 11651
First Posted:
May 5, 2010
Last Update Posted:
Nov 18, 2015
Last Verified:
Nov 1, 2015