ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00925769
Collaborator
(none)
32
2
1
59
16
0.3
Study Details
Study Description
Brief Summary
This 2 part study will evaluate the safety and efficacy of a combination of Avastin, Tarceva and Xeloda (ATX) as second-line treatment in patients with locally advanced and/or metastatic pancreatic cancer. In the first part of the study, cohorts of patients will receive escalating doses of combination treatment to determine the maximum tolerated dose. The recommended dose will be used in the second part of the study to determine the efficacy of the ATX regime, in terms of its effect on disease progression. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Study to Evaluate the Safety and Effect on Disease Progression of Triple Combination Treatment With Erlotinib (Tarceva), Bevacizumab (Avastin), and Capecitabine (Xeloda) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer (REBECA-Trial).
Study Start Date
:
Jan 1, 2009
Actual Primary Completion Date
:
Dec 1, 2013
Actual Study Completion Date
:
Dec 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: bevacizumab [Avastin]
Escalating doses of 5/10mg/kg q2w
Drug: capecitabine [Xeloda]
Escalating doses of 500/650/750/900mg/m2 bid
Drug: erlotinib [Tarceva]
Escalating doses of 100/150mg daily
|
Outcome Measures
Primary Outcome Measures
- Part 1: Maximum Tolerated Dose (MTD) of Capecitabine [Up to Week 6 (Cycle 1-3)]
MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33 percent (%) of participants of the same quality category. DLT was defined as any greater than or equal to (>=) Grade (G) 3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to adverse events (AEs).
- Part 1: MTD of Erlotinib [Up to Week 6 (Cycle 1-3)]
MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.
- Part 1: MTD of Bevacizumab [Up to Week 6 (Cycle 1-3)]
MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.
- Part 1: Preliminary Recommended Dose (PRD) of Capecitabine for Part 2 [Up to Week 6 (Cycle 1-3)]
Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
- Part 1: PRD of Erlotinib for Part 2 [Up to Week 6 (Cycle 1-3)]
Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
- Part 1: PRD of Bevacizumab for Part 2 [Up to Week 6 (Cycle 1-3)]
Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Secondary Outcome Measures
- Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR]) [CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)]
- Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR) [CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)]
- Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR) [CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)]
- Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR) [CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)]
- Part 2: Percentage of Participants Free From Disease Progression [Month 6]
As per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions (target and non-target lesions) or the unequivocal progression of existing non-target lesions.
- Part 2: Percentage of Participants With Disease Control [From baseline thereafter, every 6 weeks (±7 days), then 1 week after last dose (follow-up), thereafter every 6 weeks (±7 days) until disease progression (up to Week 259)]
A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) during the assessment. As per RECIST v1.1, CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
- Part 2: Percentage of Participants With Clinical Benefit Response [One week before start of study treatment and weekly until disease progression or death (Up to Week 259)]
Clinical benefit response was defined as a composite of pain control, Karnofsky performance status (KPS), and weight. The KPS allows participants to be classified as per their functional impairment (abnormal function). It was recorded on an 11-point scale; 0= "dead" to 100= "Normal, no complaints, no evidence of disease" and sub-divided to 3 categories; 0 to 40 = "Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing"; 50 to 70= "Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed and 80 to 100= "Able to carry on normal activity; no special care is needed".
- Part 2: Overall Survival [From baseline until death (Up to Week 259)]
Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adult patients, >=18 years of age;
-
pancreatic cancer with locally advanced and/or metastatic disease (stage IV);
-
chemonaive for metastatic or locally advanced disease;
-
ECOG performance status of 0-2.
Exclusion Criteria:
-
local (stage IA to IIB)and locally advanced (stage III) pancreatic cancer;
-
previous exposure to Avastin, Tarceva or Xeloda;
-
other primary tumor within the last 5 years prior to enrollment, except for adequately treated cancer in situ of cervix, or basal cell skin cancer;
-
current or recent chronic use of aspirin (>325 mg/day) or full therapeutic dose of anticoagulants or thrombolytic agents.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vienna | Austria | 1100 | ||
| 2 | Wien | Austria | 1130 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00925769
Other Study ID Numbers:
- ML20784
- 2008-004444-36
First Posted:
Jun 22, 2009
Last Update Posted:
Aug 7, 2015
Last Verified:
Jul 1, 2015
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Thirty two (32) participants were included however, 2 participants discontinued before reaching the end of the evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose due to progressive disease. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 milligrams (mg) of erlotinib (ERL) tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 milligrams per kilogram (mg/kg) of bevacizumab (BEV) intravenous (IV) infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 milligrams per square meter (mg/m^2) of capecitabine (CAP) tablet twice daily (BID) within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Period Title: Overall Study | ||||||
| STARTED | 6 | 6 | 6 | 6 | 3 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 6 | 6 | 6 | 3 | 3 |
Baseline Characteristics
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (Dose levels [DL]-1, 2, 3, 4, 5 and 6) were administered either oral 100 mg or 150 mg of erlotinib tablet daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Overall Participants | 30 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
63.9
(8.4)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
15
50%
|
| Male |
15
50%
|
Outcome Measures
| Title | Part 1: Maximum Tolerated Dose (MTD) of Capecitabine |
|---|---|
| Description | MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33 percent (%) of participants of the same quality category. DLT was defined as any greater than or equal to (>=) Grade (G) 3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to adverse events (AEs). |
| Time Frame | Up to Week 6 (Cycle 1-3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. |
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 30 |
| Number [mg/m^2 BID] |
900
|
| Title | Part 1: MTD of Erlotinib |
|---|---|
| Description | MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. |
| Time Frame | Up to Week 6 (Cycle 1-3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. |
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 30 |
| Number [mg/day] |
NA
|
| Title | Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR]) |
|---|---|
| Description | |
| Time Frame | CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 6 | 6 | 6 | 6 | 3 | 3 |
| Erlotinib (n=6,6,6,6,3,3) |
1.50
(1.21)
|
0.95
(0.58)
|
0.68
(0.34)
|
0.93
(0.63)
|
0.58
(0.15)
|
1.69
(0.67)
|
| OSI-420 (n=6,6,6,6,3,3) |
0.09
(0.07)
|
0.05
(0.03)
|
0.04
(0.02)
|
0.06
(0.04)
|
0.03
(0.01)
|
0.10
(0.02)
|
| Capecitabine (n=6,6,6,6,3,3) |
1.69
(1.22)
|
1.13
(0.61)
|
4.89
(4.23)
|
5.48
(4.51)
|
9.47
(5.19)
|
9.9
(5.01)
|
| 5'-DFCR (n=5,5,6,6,3,3) |
3.5
(3.02)
|
4.28
(1.61)
|
11.46
(5.32)
|
6.26
(2.05)
|
5.44
(2.43)
|
4.15
(1.24)
|
| 5'-DFUR (n=4,5,6,6,3,3) |
7.9
(4.41)
|
7.3
(2.74)
|
6.17
(2.63)
|
7.24
(3.35)
|
3.28
(0.72)
|
5.1
(2.35)
|
| Title | Part 1: MTD of Bevacizumab |
|---|---|
| Description | MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. |
| Time Frame | Up to Week 6 (Cycle 1-3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. |
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 30 |
| Number [mg/kg once every 2 weeks (Q2W)] |
NA
|
| Title | Part 1: Preliminary Recommended Dose (PRD) of Capecitabine for Part 2 |
|---|---|
| Description | Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2. |
| Time Frame | Up to Week 6 (Cycle 1-3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. |
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 30 |
| Number [mg/m^2 BID] |
800
|
| Title | Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR) |
|---|---|
| Description | |
| Time Frame | CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 6 | 6 | 6 | 6 | 3 | 3 |
| Erlotinib (n=6,6,6,6,3,3) |
2.50
|
2.00
|
2.00
|
3.00
|
5.00
|
2.00
|
| OSI-420 (n=6,6,6,6,3,3) |
3.00
|
2.00
|
2.00
|
7.00
|
6.00
|
4.00
|
| Capecitabine (n=6,6,6,6,3,3) |
0.5
|
1
|
1.5
|
0.75
|
1
|
0.5
|
| 5'-DFCR (n=5,5,6,6,3,3) |
0.5
|
1
|
1.5
|
1
|
1
|
1.5
|
| 5'-DFUR (n=4,5,6,6,3,3) |
1
|
1.5
|
1.5
|
1.5
|
1
|
1.5
|
| Title | Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR) |
|---|---|
| Description | |
| Time Frame | CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 6 | 6 | 6 | 6 | 3 | 3 |
| Erlotinib (n=6,6,6,6,3,3) |
0.37
(0.36)
|
0.31
(0.19)
|
0.23
(0.11)
|
0.39
(0.39)
|
0.23
(0.02)
|
0.52
(0.19)
|
| OSI-420 (n=6,6,6,6,3,3) |
0.04
(0.06)
|
0.02
(0.01)
|
0.01
(0.01)
|
0.04
(0.04)
|
0.01
(0.00)
|
0.04
(0.01)
|
| Capecitabine (n=6,6,6,6,3,3) |
0.05
(0.06)
|
0.2
(0.2)
|
0.17
(0.15)
|
0.06
(0.03)
|
0.29
(0.26)
|
0.17
(0.1)
|
| 5'-DFCR (n=5,5,6,6,3,3) |
0.23
(0.23)
|
0.08
(0.04)
|
0.64
(0.6)
|
0.75
(0.89)
|
0.99
(1.22)
|
0.3
(0.1)
|
| 5'-DFUR (n=4,5,6,6,3,3) |
2.54
(0.14)
|
1.03
(1.05)
|
0.77
(0.92)
|
0.58
(0.49)
|
0.14
(0.08)
|
0.14
(0.05)
|
| Title | Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR) |
|---|---|
| Description | |
| Time Frame | CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 6 | 6 | 6 | 6 | 3 | 3 |
| Erlotinib (n=6,6,6,6,3,3) |
15.81
(12.91)
|
11.06
(5.41)
|
9.15
(4.39)
|
13.07
(11.03)
|
8.54
(1.96)
|
19.88
(4.75)
|
| OSI-420 (n=6,6,6,6,3,3) |
1.15
(1.21)
|
0.48
(0.35)
|
0.41
(0.18)
|
0.99
(0.73)
|
0.36
(0.03)
|
1.42
(0.17)
|
| Capecitabine (n=6,6,6,6,3,3) |
1.43
(1.02)
|
1.63
(1.01)
|
5.88
(6.28)
|
5.28
(3.25)
|
13.63
(8.63)
|
9.74
(3.02)
|
| 5'-DFCR (n=5,5,6,6,3,3) |
3.97
(2.65)
|
7.01
(1.89)
|
20.27
(11.53)
|
9.35
(3.26)
|
12.63
(9.89)
|
8.06
(2.14)
|
| 5'-DFUR (n=4,5,6,6,3,3) |
15.42
(9.45)
|
13.58
(7.84)
|
9.76
(4.60)
|
10.86
(4.96)
|
5.17
(0.89)
|
8.53
(1.87)
|
| Title | Part 2: Percentage of Participants Free From Disease Progression |
|---|---|
| Description | As per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions (target and non-target lesions) or the unequivocal progression of existing non-target lesions. |
| Time Frame | Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Part 2: Percentage of Participants With Disease Control |
|---|---|
| Description | A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) during the assessment. As per RECIST v1.1, CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
| Time Frame | From baseline thereafter, every 6 weeks (±7 days), then 1 week after last dose (follow-up), thereafter every 6 weeks (±7 days) until disease progression (up to Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Part 2: Percentage of Participants With Clinical Benefit Response |
|---|---|
| Description | Clinical benefit response was defined as a composite of pain control, Karnofsky performance status (KPS), and weight. The KPS allows participants to be classified as per their functional impairment (abnormal function). It was recorded on an 11-point scale; 0= "dead" to 100= "Normal, no complaints, no evidence of disease" and sub-divided to 3 categories; 0 to 40 = "Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing"; 50 to 70= "Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed and 80 to 100= "Able to carry on normal activity; no special care is needed". |
| Time Frame | One week before start of study treatment and weekly until disease progression or death (Up to Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Part 2: Overall Survival |
|---|---|
| Description | Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive. |
| Time Frame | From baseline until death (Up to Week 259) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented. |
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Part 1: PRD of Erlotinib for Part 2 |
|---|---|
| Description | Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2. |
| Time Frame | Up to Week 6 (Cycle 1-3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. |
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 30 |
| Number [mg/day] |
150
|
| Title | Part 1: PRD of Bevacizumab for Part 2 |
|---|---|
| Description | Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2. |
| Time Frame | Up to Week 6 (Cycle 1-3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-protocol population. |
| Arm/Group Title | Triple Combination (Bevacizumab/Erlotinib/Capecitabine) |
|---|---|
| Arm/Group Description | Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. |
| Measure Participants | 30 |
| Number [mg/kg Q2W] |
10
|
Adverse Events
| Time Frame | From screening up to 30 days after the last chemotherapy treatment. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 | ||||||
| Arm/Group Description | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. | ||||||
All Cause Mortality |
||||||||||||
| ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 | |||||||
| Affected / at Risk (%) | # Events | 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) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 2/6 (33.3%) | 4/6 (66.7%) | 5/6 (83.3%) | 3/3 (100%) | 3/3 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anemia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Bilirubinaemia | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Embolism pulmonary | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hyponatremia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Myocardial infarction | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Diarrhoea | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Dysphagia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Gastrointestinal haemorrhage | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Haemorrhage rectum | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Intestinal stenosis | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Nausea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Vomiting | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| General disorders | ||||||||||||
| Fatigue | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Fever | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Pain | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Syncope | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Hepatic function abnormal | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Infection | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Sepsis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Skeletal pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Aphasia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Vertigo | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Dyspnoea | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Pneumonia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Dermatitis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Thrombophlebitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| ERL+BEV+CAP Dose Level-1 | ERL+BEV+CAP Dose Level-2 | ERL+BEV+CAP Dose Level-3 | ERL+BEV+CAP Dose Level-4 | ERL+BEV+CAP Dose Level-5 | ERL+BEV+CAP Dose Level-6 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 5/6 (83.3%) | 6/6 (100%) | 6/6 (100%) | 3/3 (100%) | 3/3 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anemia | 2/6 (33.3%) | 0/6 (0%) | 2/6 (33.3%) | 3/6 (50%) | 1/3 (33.3%) | 1/3 (33.3%) | ||||||
| Bilirubin | 1/6 (16.7%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Coagulation time decreased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Epistaxis | 1/6 (16.7%) | 1/6 (16.7%) | 3/6 (50%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Gingival bleeding | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hypocalcaemia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hypokalaemia | 2/6 (33.3%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hypoproteinemia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Thrombocytopenia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Thrombosis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Endocrine disorders | ||||||||||||
| Hyperthyroidism | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Eye disorders | ||||||||||||
| Conjunctivitis | 0/6 (0%) | 3/6 (50%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain | 3/6 (50%) | 4/6 (66.7%) | 3/6 (50%) | 2/6 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Cheilitis | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Colitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Constipation | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Diarrhoea | 2/6 (33.3%) | 4/6 (66.7%) | 4/6 (66.7%) | 4/6 (66.7%) | 0/3 (0%) | 2/3 (66.7%) | ||||||
| Dyspepsia | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Dysphagia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Flatulence | 1/6 (16.7%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Gastrointestinal disorder nos | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hematemesis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hiccup | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Melena | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Mouth dry | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Nausea | 4/6 (66.7%) | 2/6 (33.3%) | 4/6 (66.7%) | 4/6 (66.7%) | 2/3 (66.7%) | 2/3 (66.7%) | ||||||
| Esophagitis | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Stomatitis | 1/6 (16.7%) | 1/6 (16.7%) | 3/6 (50%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Toothache | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Vomiting | 1/6 (16.7%) | 3/6 (50%) | 4/6 (66.7%) | 4/6 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | ||||||
| General disorders | ||||||||||||
| Back pain | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Common cold | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Exsiccosis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Fatigue | 6/6 (100%) | 3/6 (50%) | 3/6 (50%) | 3/6 (50%) | 2/3 (66.7%) | 2/3 (66.7%) | ||||||
| Fever | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Leg pain | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Oedema | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Oedema mouth | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Oedema peripheral | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Pain | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Rigors | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Syncope | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Temperature changed sensation | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Ascites | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hepatic function abnormal | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Herpes simplex | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Infection | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Moniliasis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Skin infection | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Wound dehiscence | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Investigations | ||||||||||||
| C- reactive protein positive | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Appetite loss | 4/6 (66.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 4/6 (66.7%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Diabetes mellitus | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Hyperuricemia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Weight decrease | 1/6 (16.7%) | 0/6 (0%) | 2/6 (33.3%) | 3/6 (50%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Muscle weakness | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Skeletal pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Dysphonia | 1/6 (16.7%) | 0/6 (0%) | 2/6 (33.3%) | 2/6 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | ||||||
| Headache | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Neuropathy peripheral | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Taste perversion | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Vertigo | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/3 (66.7%) | 1/3 (33.3%) | ||||||
| Psychiatric disorders | ||||||||||||
| Anxiety | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Depression | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Sleep disorder | 1/6 (16.7%) | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Albuminuria | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Urinary tract infection | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 1/3 (33.3%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Genital ulceration | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Vaginitis | 2/6 (33.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Bronchitis | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Coughing | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Dyspnoea | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Increased pulmonary secretion | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Rhinitis | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 2/3 (66.7%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Alopecia | 2/6 (33.3%) | 2/6 (33.3%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Bullous eruption | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Dermatitis | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Mucosis left breast | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Palmar-plantar erythrodyesthesia | 2/6 (33.3%) | 5/6 (83.3%) | 3/6 (50%) | 3/6 (50%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Paronychia | 0/6 (0%) | 2/6 (33.3%) | 0/6 (0%) | 2/6 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Pruritus | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Rash | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Rash erythematous | 3/6 (50%) | 5/6 (83.3%) | 4/6 (66.7%) | 4/6 (66.7%) | 2/3 (66.7%) | 2/3 (66.7%) | ||||||
| Skin discolouration | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Skin dry | 0/6 (0%) | 3/6 (50%) | 0/6 (0%) | 2/6 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | ||||||
| Skin reaction localized | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Sweating increased | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Hypertension | 1/6 (16.7%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | ||||||
| Hypertension aggravated | 2/6 (33.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 0/3 (0%) | 0/3 (0%) | ||||||
| Thrombophlebitis | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/3 (0%) | 0/3 (0%) | ||||||
| 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/3 (0%) | 1/3 (33.3%) | |||||||
Limitations/Caveats
Planned Part 2 of the study was not implemented and outcome measures related to Part 2 were not analyzed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-LaRoche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00925769
Other Study ID Numbers:
- ML20784
- 2008-004444-36
First Posted:
Jun 22, 2009
Last Update Posted:
Aug 7, 2015
Last Verified:
Jul 1, 2015