Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma
Study Details
Study Description
Brief Summary
The purpose of this study is to see whether a drug called regorafenib might be effective in treating angiosarcoma. This study is for patients who have angiosarcoma that has gotten worse after they received chemotherapy. Regorafenib is a type of drug called a kinase inhibitor. Regorafenib interferes with how some kinase proteins work. Some of these kinases in cancer cells might normally help the cancer cells grow or form new blood vessels that could feed a growing tumor. By blocking these proteins, regorafenib may help stop the growth of certain cancers.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To define the progression-free survival (PFS) at 4 months with daily oral regorafenib (160 mg) in previously treated locally advanced/metastatic angiosarcoma patients
SECONDARY OBJECTIVES:
-
Progression-free rate at 3 and 6 months. II. Progression-free survival. III. Overall survival (up to 5 years). IV. Response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1).
-
Rate and duration of tumor control (complete response [CR] + partial response [PR] + stable disease [SD]).
-
Safety/tolerability of regorafenib.
OUTLINE:
Patients receive regorafenib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 5 years.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (regorafenib) Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: regorafenib
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) at 4 Months [At 4 months (of treatment)]
The progression-free survival (PFS) at 4 months will be defined as the number of patients with progression absent at 4 months divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first and will be estimated using Kaplan-Meier methods and reported as a survival probability. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): > 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD.
Secondary Outcome Measures
- Progression-Free Survival (PFS) at 3 and 6 Months [Assessed at 3 months and 6 months]
The progression-free survival (PFS) at 3 and 6 months will be defined as the number of patients with progression absent at 3 months and 6 months divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first and will be estimated using Kaplan-Meier methods and reported as a survival probability. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): > 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD.
- Median Progression-free Survival (PFS) [The duration of time from start of treatment until time of progression, up to 5 years]
The median progression-free rate (PFR) will be defined as the number of patients with progression absent divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first for up to 5 years and will be estimated using Kaplan-Meier methods. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): > 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD.
- Overall Survival [From start of treatment up to 5 years]
Overall survival will be defined as the time from start of treatment until death from any cause and will be estimated using Kaplan-Meier methods and reported as a survival probability. Patients that are alive at the time of data analysis will be censored at the date of known survival status.
- Response Rate [At baseline and after every 2 cycles, up to 12 cycles where one cycle is 28 days]
Imaging (such as a CT scan) will be done at baseline (within 4 weeks before the first dose) then after every 2 cycles while on treatment for tumor response evaluation. Response will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Best response of each patient will be used and responses will be defined as the following: Complete response (CR): Disappearance of all target lesions Partial response (PR): > 30% decrease in the baseline sum diameters of target lesions
- Rate of Tumor Control [At baseline and after every 2 cycles, up to 12 cycles where one cycle is 28 days]
Imaging will be used at baseline then after every 2 cycles while on treatment to measure tumor size and response to treatment, the data collected from all patients on study will be used to calculate the rate and duration of tumor control. Response will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Response and stable disease will be defined as the following: Complete response (CR): Disappearance of all target lesions Partial response (PR): > 30% decrease in the baseline sum diameters of target lesions Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
- Number of Grade 1, 2, 3, 4, and 5 Related Adverse Events Observed During Study Treatment (Defined by CTCAE v 4.0) [From treatment initiation though 30 days post the last treatment for a max of 12 cycles where one cycle is 28 days]
Overall worst grade related toxicity (number of patients) was collected from the start of treatment until 30 days post the last treatment where patients were treated until progressive disease or unacceptable toxicity or patient withdrawal of treatment. All Adverse events that were determined to be at least possibly related to treatment are reported. All adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The severity of an AE is graded as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Life expectancy of at least 4 months
-
Histologically confirmed angiosarcoma
-
Tumor deemed unresectable or metastatic
-
Measurable disease per RECIST v 1.1
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
-
Progressive disease under last palliative therapy with a history of prior ifosfamide, doxorubicin or taxane therapy for angiosarcoma; up to 4 prior therapies are allowed
-
All acute toxic effects of any prior treatment have resolved to grade 1 or less (by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v 4.0) at the time of registration; NOTE: Exceptions to this criterion will include alopecia and fatigue
-
Total bilirubin =< 1.5 x the upper limits of normal (ULN)
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
-
Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer)
-
Lipase =< 1.5 x the ULN
-
Serum creatinine =< 1.5 x the ULN
-
International normalized ratio (INR)/partial thromboplastin time (PTT) < 1.5 x ULN
-
Platelet count > 100000/mm^3
-
Hemoglobin > 9 g/dL
-
Absolute neutrophil count > 1500/mm^3
-
If baseline urine protein creatinine (UPC) >= 1, a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < grade 3 (> 3.5 g/24 hours) to be eligible
-
NOTE: Blood transfusion to meet the above criteria will not be allowed; NOTE: Patients who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
-
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as age
= 50 years and no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
-
Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at registration until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator
-
Subject must be able to swallow and retain oral medication
-
Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure
Exclusion Criteria:
-
Uncontrolled hypertension (systolic pressure > 140 mmHg or diastolic pressure > 90 mmHg on repeated measurement) despite optimal medical management
-
Active or clinically significant cardiac disease including:
-
Congestive heart failure - New York Heart Association > class II
-
Active coronary artery disease
-
Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
-
Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before registration, or myocardial infarction within 6 months before registration
-
Evidence or history of bleeding diathesis or coagulopathy
-
Any hemorrhage or bleeding event grade 3 within 4 weeks prior to registration
-
Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months of informed consent
-
Subjects with any previously untreated or concurrent cancer unrelated to angiosarcoma; NOTE: Exceptions include cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed; all treatments must have been completed at least 3 years prior to registration
-
Patients with pheochromocytoma
-
Patients with severe hepatic impairment (Child-Pugh class C)
-
Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
-
Ongoing infection > grade 2
-
Evidence of significant central nervous system disease including seizure disorder requiring medication, symptomatic metastatic brain or meningeal tumors
-
Presence of a non-healing wound, non-healing ulcer, or bone fracture
-
Renal failure requiring hemo-or peritoneal dialysis
-
Dehydration > grade 1
-
Interstitial lung disease with ongoing signs and symptoms at the time of registration
-
Pleural effusion or ascites that causes respiratory compromise (>= grade 2 dyspnea)
-
History of organ allograft (including corneal transplant)
-
Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
-
Any malabsorption condition
-
Evidence of abdominal fistula, gastrointestinal (GI) perforation or intraabdominal abscess
-
Women who are pregnant or breast-feeding
-
Concurrent anti-cancer therapy (chemotherapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib)
-
Prior use of regorafenib
-
Prior use of sorafenib
-
Use of cytotoxic chemotherapy within 21 days of registration
-
Use of targeted therapy within two half-lives of registration
-
Radiation directed at target lesion within 28 days of registration
-
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before registration
-
Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids; NOTE: Prophylactic anticoagulation as described below is allowed:
-
Low dose warfarin (1 mg orally, once daily) with prothrombin time (PT)-international normalized ratio (INR) =< 1.5 x ULN is permitted; infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy; therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes
-
Low dose aspirin (=< 100 mg daily)
-
Prophylactic doses of heparin
-
Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
-
Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Sarcoma Oncology Center | Santa Monica | California | United States | 90403 |
2 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224-9980 |
3 | Northwestern University | Chicago | Illinois | United States | 60611 |
4 | University of Iowa | Iowa City | Iowa | United States | 52246 |
5 | University of Minnesota Medical Center-Fairview | Minneapolis | Minnesota | United States | 55455 |
6 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
7 | Washington University-St. Louis | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Northwestern University
- Bayer
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Mark Agulnik, M.D., Northwestern University
Study Documents (Full-Text)
More Information
Publications
None provided.- NU 13S02
- NCI-2013-02278
- STU00087654
- ONC-2013-129
- NU 13S02
- P30CA060553
Study Results
Participant Flow
Recruitment Details | The study was opened for enrollment March 12, 2014 with the first patient starting treatment June 13, 2014. A total of 31 patients were treated under the protocol. The study was permanently suspended to further enrollment August 5, 2019. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Period Title: 2 Cycles of Treatment | |
STARTED | 31 |
Attempted 1st Cycle | 31 |
Attempted 2nd Cycle | 23 |
COMPLETED | 23 |
NOT COMPLETED | 8 |
Period Title: 2 Cycles of Treatment | |
STARTED | 23 |
Assessed for First Response | 23 |
Went on to Cycle 3 and Beyond | 13 |
COMPLETED | 13 |
NOT COMPLETED | 10 |
Period Title: 2 Cycles of Treatment | |
STARTED | 31 |
COMPLETED | 4 |
NOT COMPLETED | 27 |
Baseline Characteristics
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Overall Participants | 31 |
Age, Customized (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
64.32
(14.58)
|
Sex: Female, Male (Count of Participants) | |
Female |
16
51.6%
|
Male |
15
48.4%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
0
0%
|
Not Hispanic or Latino |
31
100%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
3
9.7%
|
White |
27
87.1%
|
More than one race |
0
0%
|
Unknown or Not Reported |
1
3.2%
|
Region of Enrollment (participants) [Number] | |
United States |
31
100%
|
Type of disease (Count of Participants) | |
Metastatic |
21
67.7%
|
Locally advanced/Unresectable |
9
29%
|
Not reported |
1
3.2%
|
Outcome Measures
Title | Progression-Free Survival (PFS) at 4 Months |
---|---|
Description | The progression-free survival (PFS) at 4 months will be defined as the number of patients with progression absent at 4 months divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first and will be estimated using Kaplan-Meier methods and reported as a survival probability. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): > 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD. |
Time Frame | At 4 months (of treatment) |
Outcome Measure Data
Analysis Population Description |
---|
8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 23 |
Number (95% Confidence Interval) [percentage of patients alive] |
52.17
|
Title | Progression-Free Survival (PFS) at 3 and 6 Months |
---|---|
Description | The progression-free survival (PFS) at 3 and 6 months will be defined as the number of patients with progression absent at 3 months and 6 months divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first and will be estimated using Kaplan-Meier methods and reported as a survival probability. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): > 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD. |
Time Frame | Assessed at 3 months and 6 months |
Outcome Measure Data
Analysis Population Description |
---|
8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 23 |
3 months |
56.52
|
6 months |
47.83
|
Title | Median Progression-free Survival (PFS) |
---|---|
Description | The median progression-free rate (PFR) will be defined as the number of patients with progression absent divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first for up to 5 years and will be estimated using Kaplan-Meier methods. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): > 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD. |
Time Frame | The duration of time from start of treatment until time of progression, up to 5 years |
Outcome Measure Data
Analysis Population Description |
---|
8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 23 |
Median (95% Confidence Interval) [months] |
5.49
|
Title | Overall Survival |
---|---|
Description | Overall survival will be defined as the time from start of treatment until death from any cause and will be estimated using Kaplan-Meier methods and reported as a survival probability. Patients that are alive at the time of data analysis will be censored at the date of known survival status. |
Time Frame | From start of treatment up to 5 years |
Outcome Measure Data
Analysis Population Description |
---|
8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 23 |
Median (95% Confidence Interval) [months] |
14.06
|
Title | Response Rate |
---|---|
Description | Imaging (such as a CT scan) will be done at baseline (within 4 weeks before the first dose) then after every 2 cycles while on treatment for tumor response evaluation. Response will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Best response of each patient will be used and responses will be defined as the following: Complete response (CR): Disappearance of all target lesions Partial response (PR): > 30% decrease in the baseline sum diameters of target lesions |
Time Frame | At baseline and after every 2 cycles, up to 12 cycles where one cycle is 28 days |
Outcome Measure Data
Analysis Population Description |
---|
8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 23 |
Complete Response |
2
6.5%
|
Partial Response |
2
6.5%
|
Title | Rate of Tumor Control |
---|---|
Description | Imaging will be used at baseline then after every 2 cycles while on treatment to measure tumor size and response to treatment, the data collected from all patients on study will be used to calculate the rate and duration of tumor control. Response will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Response and stable disease will be defined as the following: Complete response (CR): Disappearance of all target lesions Partial response (PR): > 30% decrease in the baseline sum diameters of target lesions Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study |
Time Frame | At baseline and after every 2 cycles, up to 12 cycles where one cycle is 28 days |
Outcome Measure Data
Analysis Population Description |
---|
8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 23 |
Complete Response |
2
|
Partial Response |
2
|
Stable Disease |
9
|
Title | Number of Grade 1, 2, 3, 4, and 5 Related Adverse Events Observed During Study Treatment (Defined by CTCAE v 4.0) |
---|---|
Description | Overall worst grade related toxicity (number of patients) was collected from the start of treatment until 30 days post the last treatment where patients were treated until progressive disease or unacceptable toxicity or patient withdrawal of treatment. All Adverse events that were determined to be at least possibly related to treatment are reported. All adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The severity of an AE is graded as follows: Mild (grade 1): the event causes discomfort without disruption of normal daily activities. Moderate (grade 2): the event causes discomfort that affects normal daily activities. Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Life-threatening (grade 4): the patient was at risk of death at the time of the event. Fatal (grade 5): the event caused death |
Time Frame | From treatment initiation though 30 days post the last treatment for a max of 12 cycles where one cycle is 28 days |
Outcome Measure Data
Analysis Population Description |
---|
At the time of data pull (12/02/2019) for this outcome measure two patients remained on treatment. Any subsequent AEs determined to be related to treatment for these patients is not included here. |
Arm/Group Title | Treatment (Regorafenib) |
---|---|
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO |
Measure Participants | 31 |
Grade 1 |
5
16.1%
|
Grade 2 |
3
9.7%
|
Grade 3 |
3
9.7%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
20
64.5%
|
Grade 1 |
1
3.2%
|
Grade 2 |
0
0%
|
Grade 3 |
0
0%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
30
96.8%
|
Grade 1 |
2
6.5%
|
Grade 2 |
0
0%
|
Grade 3 |
0
0%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
29
93.5%
|
Grade 1 |
14
45.2%
|
Grade 2 |
9
29%
|
Grade 3 |
3
9.7%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
5
16.1%
|
Grade 1 |
11
35.5%
|
Grade 2 |
8
25.8%
|
Grade 3 |
4
12.9%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
8
25.8%
|
Grade 1 |
1
3.2%
|
Grade 2 |
2
6.5%
|
Grade 3 |
0
0%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
28
90.3%
|
Grade 1 |
0
0%
|
Grade 2 |
1
3.2%
|
Grade 3 |
0
0%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
30
96.8%
|
Grade 1 |
10
32.3%
|
Grade 2 |
4
12.9%
|
Grade 3 |
5
16.1%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
12
38.7%
|
Grade 1 |
14
45.2%
|
Grade 2 |
2
6.5%
|
Grade 3 |
3
9.7%
|
Grade 4 |
1
3.2%
|
Number of patients who didn't experience any grade |
11
35.5%
|
Grade 1 |
7
22.6%
|
Grade 2 |
3
9.7%
|
Grade 3 |
1
3.2%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
20
64.5%
|
Grade 1 |
1
3.2%
|
Grade 2 |
0
0%
|
Grade 3 |
0
0%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
30
96.8%
|
Grade 1 |
11
35.5%
|
Grade 2 |
2
6.5%
|
Grade 3 |
1
3.2%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
17
54.8%
|
Grade 1 |
3
9.7%
|
Grade 2 |
1
3.2%
|
Grade 3 |
2
6.5%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
25
80.6%
|
Grade 1 |
0
0%
|
Grade 2 |
1
3.2%
|
Grade 3 |
0
0%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
30
96.8%
|
Grade 1 |
9
29%
|
Grade 2 |
1
3.2%
|
Grade 3 |
1
3.2%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
20
64.5%
|
Grade 1 |
14
45.2%
|
Grade 2 |
6
19.4%
|
Grade 3 |
1
3.2%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
10
32.3%
|
Grade 1 |
3
9.7%
|
Grade 2 |
8
25.8%
|
Grade 3 |
4
12.9%
|
Grade 4 |
0
0%
|
Number of patients who didn't experience any grade |
16
51.6%
|
Adverse Events
Time Frame | Adverse events were collected for each patient from the initiation of treatment up until 30 days post last dose of treatment for a maximum of 12 cycles for any patient (where 1 Cycle = 28 days). | |
---|---|---|
Adverse Event Reporting Description | Due to data collection methods, some serious adverse event (SAEs) data maybe captured within the other adverse event data information. There are patients currently on treatment and these sections will be updated with complete information at the study completion. SAEs for any patients that were screenfails (i.e., signed consent but never started study treatment) have been removed from these results. These patients were not included in the participant flow and baseline characteristics section. | |
Arm/Group Title | Treatment (Regorafenib) | |
Arm/Group Description | Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. regorafenib: Given PO | |
All Cause Mortality |
||
Treatment (Regorafenib) | ||
Affected / at Risk (%) | # Events | |
Total | 24/31 (77.4%) | |
Serious Adverse Events |
||
Treatment (Regorafenib) | ||
Affected / at Risk (%) | # Events | |
Total | 15/31 (48.4%) | |
Gastrointestinal disorders | ||
Intra-abdominal hemorrhage | 1/31 (3.2%) | 1 |
Nausea | 1/31 (3.2%) | 1 |
Nausea | 1/31 (3.2%) | 1 |
Lower gastrointestinal hemorrhage | 1/31 (3.2%) | 1 |
General disorders | ||
Intractable pain | 1/31 (3.2%) | 1 |
Fever | 1/31 (3.2%) | 1 |
Neck pain | 1/31 (3.2%) | 1 |
Infections and infestations | ||
Lung infection | 1/31 (3.2%) | 1 |
Metabolism and nutrition disorders | ||
Hyponatremia | 1/31 (3.2%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Generalized weakness | 1/31 (3.2%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Disease progression | 2/31 (6.5%) | 2 |
Tumor hemorrhage | 1/31 (3.2%) | 2 |
Nervous system disorders | ||
Peripheral sensory neuropathy | 1/31 (3.2%) | 1 |
Confusion | 1/31 (3.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnea | 1/31 (3.2%) | 1 |
Pleural Effusion | 1/31 (3.2%) | 1 |
Pleural effusion | 1/31 (3.2%) | 1 |
Dyspnea | 1/31 (3.2%) | 1 |
Skin and subcutaneous tissue disorders | ||
Skin ulceration | 1/31 (3.2%) | 1 |
Vascular disorders | ||
Vascular Disorder | 1/31 (3.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Treatment (Regorafenib) | ||
Affected / at Risk (%) | # Events | |
Total | 31/31 (100%) | |
Blood and lymphatic system disorders | ||
Anemia | 14/31 (45.2%) | |
Leukocytosis | 1/31 (3.2%) | |
Cardiac disorders | ||
Cardiac disorders - Other, specify | 2/31 (6.5%) | |
Chest pain - cardiac | 1/31 (3.2%) | |
Myocardial infarction | 1/31 (3.2%) | |
Sinus tachycardia | 1/31 (3.2%) | |
Ear and labyrinth disorders | ||
Ear and labyrinth disorders - Other, specify | 1/31 (3.2%) | |
Ear pain | 1/31 (3.2%) | |
Tinnitus | 1/31 (3.2%) | |
Endocrine disorders | ||
Hypothyroidism | 1/31 (3.2%) | |
Eye disorders | ||
Blurred vision | 1/31 (3.2%) | |
Eye disorders - Other, specify | 1/31 (3.2%) | |
Gastrointestinal disorders | ||
Abdominal pain | 6/31 (19.4%) | |
Ascites | 1/31 (3.2%) | |
Constipation | 12/31 (38.7%) | |
Diarrhea | 16/31 (51.6%) | |
Dry mouth | 8/31 (25.8%) | |
Dysphagia | 1/31 (3.2%) | |
Flatulence | 2/31 (6.5%) | |
Gastrointestinal disorders - Other, specify | 2/31 (6.5%) | |
Hemorrhoids | 1/31 (3.2%) | |
Ileus | 1/31 (3.2%) | |
Intra-abdominal hemorrhage | 1/31 (3.2%) | |
Lower gastrointestinal hemorrhage | 1/31 (3.2%) | |
Mucositis oral | 11/31 (35.5%) | |
Nausea | 16/31 (51.6%) | |
Oral dysesthesia | 3/31 (9.7%) | |
Stomach pain | 2/31 (6.5%) | |
Vomiting | 11/31 (35.5%) | |
General disorders | ||
Chills | 2/31 (6.5%) | |
Edema face | 2/31 (6.5%) | |
Edema limbs | 4/31 (12.9%) | |
Fatigue | 23/31 (74.2%) | |
Fever | 6/31 (19.4%) | |
Gait disturbance | 5/31 (16.1%) | |
General disorders and administration site conditions - Other, specify | 2/31 (6.5%) | |
Malaise | 1/31 (3.2%) | |
Non-cardiac chest pain | 1/31 (3.2%) | |
Pain | 8/31 (25.8%) | |
Infections and infestations | ||
Gum infection | 1/31 (3.2%) | |
Lung infection | 1/31 (3.2%) | |
Otitis externa | 1/31 (3.2%) | |
Otitis media | 1/31 (3.2%) | |
Peripheral nerve infection | 1/31 (3.2%) | |
Tooth infection | 1/31 (3.2%) | |
Upper respiratory infection | 2/31 (6.5%) | |
Urinary tract infection | 1/31 (3.2%) | |
Injury, poisoning and procedural complications | ||
Fall | 1/31 (3.2%) | |
Fracture | 3/31 (9.7%) | |
Hip fracture | 1/31 (3.2%) | |
Investigations | ||
Activated partial thromboplastin time prolonged | 2/31 (6.5%) | |
Alanine aminotransferase increased | 6/31 (19.4%) | |
Alkaline phosphatase increased | 7/31 (22.6%) | |
Aspartate aminotransferase increased | 7/31 (22.6%) | |
Blood bilirubin increased | 9/31 (29%) | |
Cholesterol high | 1/31 (3.2%) | |
Creatinine increased | 7/31 (22.6%) | |
INR increased | 5/31 (16.1%) | |
Investigations - Other, specify | 2/31 (6.5%) | |
Lipase increased | 3/31 (9.7%) | |
Lymphocyte count decreased | 16/31 (51.6%) | |
Neutrophil count decreased | 1/31 (3.2%) | |
Platelet count decreased | 11/31 (35.5%) | |
Serum amylase increased | 1/31 (3.2%) | |
Weight loss | 6/31 (19.4%) | |
White blood cell decreased | 1/31 (3.2%) | |
Metabolism and nutrition disorders | ||
Anorexia | 13/31 (41.9%) | |
Dehydration | 1/31 (3.2%) | |
Hyperglycemia | 6/31 (19.4%) | |
Hyperkalemia | 4/31 (12.9%) | |
Hypernatremia | 1/31 (3.2%) | |
Hypoalbuminemia | 16/31 (51.6%) | |
Hypocalcemia | 13/31 (41.9%) | |
Hypoglycemia | 1/31 (3.2%) | |
Hypokalemia | 8/31 (25.8%) | |
Hypomagnesemia | 5/31 (16.1%) | |
Hyponatremia | 10/31 (32.3%) | |
Hypophosphatemia | 1/31 (3.2%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 4/31 (12.9%) | |
Back pain | 7/31 (22.6%) | |
Chest wall pain | 1/31 (3.2%) | |
Flank pain | 1/31 (3.2%) | |
Generalized muscle weakness | 5/31 (16.1%) | |
Muscle weakness lower limb | 1/31 (3.2%) | |
Musculoskeletal and connective tissue disorder - Other, specify | 2/31 (6.5%) | |
Myalgia | 4/31 (12.9%) | |
Neck pain | 3/31 (9.7%) | |
Pain in extremity | 8/31 (25.8%) | |
Trismus | 1/31 (3.2%) | |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 2/31 (6.5%) | |
Tumor pain | 2/31 (6.5%) | |
Nervous system disorders | ||
Ataxia | 2/31 (6.5%) | |
Dizziness | 6/31 (19.4%) | |
Dysgeusia | 3/31 (9.7%) | |
Headache | 9/31 (29%) | |
Movements involuntary | 1/31 (3.2%) | |
Paresthesia | 2/31 (6.5%) | |
Peripheral sensory neuropathy | 6/31 (19.4%) | |
Syncope | 1/31 (3.2%) | |
Psychiatric disorders | ||
Anxiety | 2/31 (6.5%) | |
Confusion | 3/31 (9.7%) | |
Insomnia | 8/31 (25.8%) | |
Renal and urinary disorders | ||
Acute kidney injury | 1/31 (3.2%) | |
Urinary frequency | 1/31 (3.2%) | |
Urinary incontinence | 1/31 (3.2%) | |
Urinary retention | 1/31 (3.2%) | |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 6/31 (19.4%) | |
Dyspnea | 9/31 (29%) | |
Epistaxis | 3/31 (9.7%) | |
Hoarseness | 6/31 (19.4%) | |
Laryngeal mucositis | 1/31 (3.2%) | |
Nasal congestion | 1/31 (3.2%) | |
Pleural effusion | 1/31 (3.2%) | |
Postnasal drip | 1/31 (3.2%) | |
Respiratory, thoracic and mediastinal disorders - Other, specify | 1/31 (3.2%) | |
Sore throat | 3/31 (9.7%) | |
Skin and subcutaneous tissue disorders | ||
Alopecia | 3/31 (9.7%) | |
Dry skin | 1/31 (3.2%) | |
Erythema multiforme | 2/31 (6.5%) | |
Palmar-plantar erythrodysesthesia syndrome | 12/31 (38.7%) | |
Pruritus | 1/31 (3.2%) | |
Rash acneiform | 3/31 (9.7%) | |
Rash maculo-papular | 7/31 (22.6%) | |
Skin and subcutaneous tissue disorders - Other, specify | 9/31 (29%) | |
Skin ulceration | 2/31 (6.5%) | |
Vascular disorders | ||
Hypertension | 17/31 (54.8%) | |
Hypotension | 4/31 (12.9%) | |
Vascular disorders - Other, specify | 1/31 (3.2%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE 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 | Mary Mulcahy, MD |
---|---|
Organization | Northwestern University |
Phone | 312 695 4440 |
m-mulcahy@northwestern.edu |
- NU 13S02
- NCI-2013-02278
- STU00087654
- ONC-2013-129
- NU 13S02
- P30CA060553