AVAGAST: A Study of Bevacizumab in Combination With Capecitabine and Cisplatin as First-line Therapy in Patients With Advanced Gastric Cancer
Study Details
Study Description
Brief Summary
This study will compare treatment with bevacizumab in combination with capecitabine and cisplatin versus placebo in combination with capecitabine and cisplatin, as first-line therapy in patients with locally advanced or metastatic gastric cancer who had not received prior chemotherapy for advanced or metastatic disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This is a 2 arm, randomized, double-blind, multicenter phase III study. Patients will be randomized (1:1) to capecitabine/cisplatin plus bevacizumab or capecitabine/cisplatin plus placebo. This is an event-driven trial with the primary analysis planned after approximately 517 deaths had been observed. After the primary analysis, the study will remain open and patients can continue with study treatment until progressive disease or earlier at the investigator's discretion. After discontinuation of the last patient, the study will end globally.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bevacizumab Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
Drug: Bevacizumab
Intravenous bevacizumab 7.5 mg/kg once every 3 weeks, given until disease progression or unmanageable toxicity.
Drug: Capecitabine
Oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, given until disease progression or unmanageable toxicity.
Drug: Cisplatin
Cisplatin 80 mg/m˄2 as a 2 hr intravenous infusion with hyper-hydration and pre-medication (steroids and anti-emetics), given every 3 weeks for a maximum of 6 cycles or until disease progression or unmanageable toxicity.
Drug: 5-fluorouracil
For participants with difficulty swallowing, malabsorption, or other conditions that could affect intake of oral capecitabine medication, 5-fluorouracil was administered instead, at a dose of 800 mg/m˄2/day as a continuous intravenous infusion over 5 days (days 1 to 5 of each cycle), every 3 weeks.
|
| Placebo Comparator: Placebo Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
Drug: Capecitabine
Oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, given until disease progression or unmanageable toxicity.
Drug: Cisplatin
Cisplatin 80 mg/m˄2 as a 2 hr intravenous infusion with hyper-hydration and pre-medication (steroids and anti-emetics), given every 3 weeks for a maximum of 6 cycles or until disease progression or unmanageable toxicity.
Drug: Placebo
Intravenous placebo every 3 weeks, given until disease progression or unmanageable toxicity.
Drug: 5-fluorouracil
For participants with difficulty swallowing, malabsorption, or other conditions that could affect intake of oral capecitabine medication, 5-fluorouracil was administered instead, at a dose of 800 mg/m˄2/day as a continuous intravenous infusion over 5 days (days 1 to 5 of each cycle), every 3 weeks.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival [From randomization until death, up to 26 months]
The primary efficacy endpoint for this study was overall survival (time to death), defined as the time between randomization and the date of death irrespective of the cause of death. Patients for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. Median survival was estimated by the Kaplan-Meier method.
Secondary Outcome Measures
- Progression-free Survival [From randomization until disease progression or death, up to 26 months.]
Progression-free survival (PFS) is defined as the time between randomization and the date of first documented disease progression or death, whichever occurs first. Patients who neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow up for progression of disease. Median PFS was estimated using the Kaplan-Meier method.
- Progression-free Survival During First-line Therapy [From randomization until 28-days after the last study treatment was administered, up to 26 months.]
Progression-free survival (PFS) during first-line therapy is defined as the time between randomization and the date of first documented disease progression or death, whichever occurs first and only if it occurs no later than 28 days after last confirmed intake of any study medication and only if it occurs before the start of non-study antineoplastic treatment. Participants who did not progress or die in this interval or were lost to follow-up were censored at the date of the last tumor assessment within this time window. Median PFS was estimated using the Kaplan-Meier method.
- Time to Disease Progression [From randomization until disease progression; assessed every 6 weeks for the first year and every 12 weeks thereafter, up to 26 months.]
Time to progression is defined as the time from randomization to the first occurrence of progressive disease (PD). PD was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and defined as at least a 20% increase in the sum of the longest diameter of target lesions, or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Patients with no PD at study completion (including those who died before PD) were censored at the date of the last tumor assessment. Median time to PD was estimated using the Kaplan-Meier method.
- Participants With a Best Overall Response of Complete or Partial Response [From randomization until the end of study, up to 26 months.]
Best overall response during first-line therapy is defined as the occurrence of either a confirmed complete (CR) or a partial (PR) best overall response, as determined by the RECIST criteria. CR is defined as the disappearance of all target and non-target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions and no new or progression of non-target lesions, or the disappearance of all target lesions and persistence of one or more non-target lesion(s).
- Duration of Response [From randomization to the end of study, up to 26 months]
Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only be calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow up for progression of disease during first line therapy. Median duration of response was estimated using the Kaplan-Meier method.
- Participants With Disease Control [From randomization until the end of study, up to 26 months.]
Disease control for participants with measurable disease was defined as a complete response (CR), partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the RECIST criteria. For participants without measurable disease, disease control was defined as no disease progression for ≥ 6 weeks.
- Participants With Adverse Events [From randomization until 3 months after last dose (up to 26 months)]
The intensity of Adverse Events (AEs) was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 on a five-point scale from Grade 1 (Mild) to Grade 5 (Death). A serious AE (SAE) was defined as any event that is fatal, life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent obtained prior to any study specific procedures.
-
Age ≥ 18 years.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
-
Life expectancy of at least 3 months.
-
Able to comply with the protocol.
-
Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable, locally advanced, or metastatic disease, not amenable to curative therapy.
-
Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST).
-
Patient not receiving anticoagulant medication must have an International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x Upper Limit of Normal (ULN) within 7 days prior to randomisation.
Exclusion Criteria:
-
Previous chemotherapy for locally advanced or metastatic gastric cancer. Patients may have received prior neoadjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to randomisation.
-
Previous platinum or anti-angiogenic therapy (ie, anti-vascular endothelial growth factor [VEGF] or VEGF receptor tyrosine kinase inhibitor, etc.).
-
Patients with locally advanced disease who are candidates for curative therapy (including operation and/or chemotherapy and/or radiotherapy).
-
Radiotherapy within 28 days of randomisation.
-
Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomisation, or anticipation of the need for major surgery during the course of the study treatment (planned elective surgery).
-
Minor surgical procedures within 2 days prior to randomisation.
-
Evidence of central nervous system (CNS) metastasis at baseline.
-
History or evidence upon physical/neurological examination of CNS disease unrelated to cancer unless adequately treated with standard medical therapy, eg, uncontrolled seizures.
-
History of another malignancy which could affect compliance with the protocol or interpretation of results.
-
Inadequate bone marrow function.
-
Inadequate liver function.
-
Inadequate renal function.
-
Uncontrolled hypertension or clinically significant (ie, active) cardiovascular disease.
-
Active infection requiring intravenous antibiotics at randomisation.
-
History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
-
Serious or non-healing wound, peptic ulcer, or (incompletely healed) bone fracture.
-
Active gastrointestinal bleeding.
-
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of randomisation.
-
Neuropathy (eg, impairment of hearing and balance) ≥ grade II according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
-
Chronic daily treatment with aspirin or clopidogrel.
-
Chronic daily treatment with oral corticosteroids; inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed.
-
Known hypersensitivity to any of the study drugs or excipients or to Chinese hamster ovary cell products or to other recombinant human or humanised antibodies.
-
Known dihydropyrimidine dehydrogenase (DPD) deficiency.
-
Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or that may affect patient compliance with the study, or place the patient at high risk from treatment complications.
-
Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
-
Pregnant or lactating females.
-
Women of childbearing potential not using effective nonhormonal (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) means of contraception.
-
Sexually active men unwilling to practice contraception during the study.
-
Current or recent (within the 28 days prior to randomisation) treatment with another investigational drug or participation in another investigational study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tower Cancer Research Fnd | Beverly Hills | California | United States | 90211-1850 |
| 2 | Moores UCSD Cancer Center | La Jolla | California | United States | 92093 |
| 3 | Kenmar Research Institute LLC | Los Angeles | California | United States | 90057 |
| 4 | USC/Norris Cancer Center | Los Angeles | California | United States | 90089 |
| 5 | Georgetown University | Washington, D.C. | District of Columbia | United States | 20007 |
| 6 | Florida Cancer Specialists | Fort Myers | Florida | United States | 33916 |
| 7 | H. Lee Moffitt Cancer | Tampa | Florida | United States | 33612 |
| 8 | Cancer Center of Kansas | Wichita | Kansas | United States | 67214-3728 |
| 9 | Methodist Cancer Center Onc | Omaha | Nebraska | United States | 68114 |
| 10 | Memorial Sloan Kettering | New York | New York | United States | 10021 |
| 11 | Duke Univ Medical Center | Durham | North Carolina | United States | 27710 |
| 12 | South Carolina Oncology Assoc | Columbia | South Carolina | United States | 10595 |
| 13 | The Sarah Cannon Research Inst | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Genentech, Inc.
- Hoffmann-La Roche
- Chugai Pharmaceutical
Investigators
- Study Director: Eric Hedrick, MD, Genentech, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AVF4200g
- BO20904
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Period Title: Overall Study | ||
| STARTED | 387 | 387 |
| Treated | 383 | 384 |
| Safety Population | 386 | 381 |
| COMPLETED | 25 | 21 |
| NOT COMPLETED | 362 | 366 |
Baseline Characteristics
| Arm/Group Title | Bevacizumab | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 387 | 387 | 774 |
| Age, Customized (participants) [Number] | |||
| <40 |
36
9.3%
|
29
7.5%
|
65
8.4%
|
| 40-65 |
241
62.3%
|
249
64.3%
|
490
63.3%
|
| ≥65 |
110
28.4%
|
109
28.2%
|
219
28.3%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
130
33.6%
|
129
33.3%
|
259
33.5%
|
| Male |
257
66.4%
|
258
66.7%
|
515
66.5%
|
Outcome Measures
| Title | Overall Survival |
|---|---|
| Description | The primary efficacy endpoint for this study was overall survival (time to death), defined as the time between randomization and the date of death irrespective of the cause of death. Patients for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. Median survival was estimated by the Kaplan-Meier method. |
| Time Frame | From randomization until death, up to 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-to-Treat population, including all randomized participants. |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 387 | 387 |
| Median (95% Confidence Interval) [months] |
12.1
|
10.1
|
| Title | Progression-free Survival |
|---|---|
| Description | Progression-free survival (PFS) is defined as the time between randomization and the date of first documented disease progression or death, whichever occurs first. Patients who neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow up for progression of disease. Median PFS was estimated using the Kaplan-Meier method. |
| Time Frame | From randomization until disease progression or death, up to 26 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 387 | 387 |
| Median (95% Confidence Interval) [months] |
6.7
|
5.3
|
| Title | Progression-free Survival During First-line Therapy |
|---|---|
| Description | Progression-free survival (PFS) during first-line therapy is defined as the time between randomization and the date of first documented disease progression or death, whichever occurs first and only if it occurs no later than 28 days after last confirmed intake of any study medication and only if it occurs before the start of non-study antineoplastic treatment. Participants who did not progress or die in this interval or were lost to follow-up were censored at the date of the last tumor assessment within this time window. Median PFS was estimated using the Kaplan-Meier method. |
| Time Frame | From randomization until 28-days after the last study treatment was administered, up to 26 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to treat. |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 387 | 387 |
| Median (95% Confidence Interval) [months] |
6.9
|
5.4
|
| Title | Time to Disease Progression |
|---|---|
| Description | Time to progression is defined as the time from randomization to the first occurrence of progressive disease (PD). PD was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and defined as at least a 20% increase in the sum of the longest diameter of target lesions, or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Patients with no PD at study completion (including those who died before PD) were censored at the date of the last tumor assessment. Median time to PD was estimated using the Kaplan-Meier method. |
| Time Frame | From randomization until disease progression; assessed every 6 weeks for the first year and every 12 weeks thereafter, up to 26 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 387 | 387 |
| Median (95% Confidence Interval) [months] |
7.0
|
5.6
|
| Title | Participants With a Best Overall Response of Complete or Partial Response |
|---|---|
| Description | Best overall response during first-line therapy is defined as the occurrence of either a confirmed complete (CR) or a partial (PR) best overall response, as determined by the RECIST criteria. CR is defined as the disappearance of all target and non-target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions and no new or progression of non-target lesions, or the disappearance of all target lesions and persistence of one or more non-target lesion(s). |
| Time Frame | From randomization until the end of study, up to 26 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Measurable Disease Population, including all randomized participants with measurable disease (per RECIST) for gastric cancer at baseline. Patients were analyzed according to the treatment groups to which they were randomized. |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 311 | 297 |
| Responders |
143
37%
|
111
28.7%
|
| Non-responders |
168
43.4%
|
186
48.1%
|
| Title | Duration of Response |
|---|---|
| Description | Duration of response during first line therapy is defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only be calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow up for progression of disease during first line therapy. Median duration of response was estimated using the Kaplan-Meier method. |
| Time Frame | From randomization to the end of study, up to 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with measurable disease at baseline who had a best overall response of complete response or partial response, and for whom duration of response data was available. |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 142 | 111 |
| Median (95% Confidence Interval) [months] |
7.1
|
5.8
|
| Title | Participants With Disease Control |
|---|---|
| Description | Disease control for participants with measurable disease was defined as a complete response (CR), partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the RECIST criteria. For participants without measurable disease, disease control was defined as no disease progression for ≥ 6 weeks. |
| Time Frame | From randomization until the end of study, up to 26 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 387 | 387 |
| Participants with Disease Control |
300
77.5%
|
271
70%
|
| Participants without Disease Control |
87
22.5%
|
116
30%
|
| Title | Participants With Adverse Events |
|---|---|
| Description | The intensity of Adverse Events (AEs) was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 on a five-point scale from Grade 1 (Mild) to Grade 5 (Death). A serious AE (SAE) was defined as any event that is fatal, life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. |
| Time Frame | From randomization until 3 months after last dose (up to 26 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population, including all patients randomized and exposed to study medication (defined as any one component of the combination). Patients are assigned to treatment groups based on the treatment they actually received. |
| Arm/Group Title | Bevacizumab | Placebo |
|---|---|---|
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. |
| Measure Participants | 386 | 381 |
| Any Adverse event |
380
98.2%
|
377
97.4%
|
| Serious AE |
134
34.6%
|
137
35.4%
|
| Grade 3/4/5 AE |
293
75.7%
|
294
76%
|
| Grade 5 AE |
18
4.7%
|
25
6.5%
|
| Deaths not due to Progression |
31
8%
|
29
7.5%
|
Adverse Events
| Time Frame | From time of very first drug intake until 91 day(s) after very last drug intake. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population: All randomized participants who were exposed to study medication (defined as any one component of the combination). | |||
| Arm/Group Title | Bevacizumab | Placebo | ||
| Arm/Group Description | Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity. | ||
All Cause Mortality |
||||
| Bevacizumab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Bevacizumab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 134/386 (34.7%) | 137/381 (36%) | ||
| Blood and lymphatic system disorders | ||||
| FEBRILE NEUTROPENIA | 13/386 (3.4%) | 13/381 (3.4%) | ||
| NEUTROPENIA | 7/386 (1.8%) | 10/381 (2.6%) | ||
| ANAEMIA | 6/386 (1.6%) | 7/381 (1.8%) | ||
| THROMBOCYTOPENIA | 2/386 (0.5%) | 3/381 (0.8%) | ||
| COAGULOPATHY | 1/386 (0.3%) | 0/381 (0%) | ||
| DISSEMINATED INTRAVASCULAR COAGULATION | 1/386 (0.3%) | 0/381 (0%) | ||
| LEUKOPENIA | 1/386 (0.3%) | 0/381 (0%) | ||
| LYMPHOPENIA | 0/386 (0%) | 1/381 (0.3%) | ||
| MICROANGIOPATHIC HAEMOLYTIC ANAEMIA | 1/386 (0.3%) | 0/381 (0%) | ||
| PANCYTOPENIA | 1/386 (0.3%) | 0/381 (0%) | ||
| SPLENIC INFARCTION | 1/386 (0.3%) | 0/381 (0%) | ||
| Cardiac disorders | ||||
| CARDIAC FAILURE | 2/386 (0.5%) | 0/381 (0%) | ||
| MYOCARDIAL INFARCTION | 1/386 (0.3%) | 1/381 (0.3%) | ||
| ACUTE MYOCARDIAL INFARCTION | 0/386 (0%) | 1/381 (0.3%) | ||
| ANGINA UNSTABLE | 1/386 (0.3%) | 0/381 (0%) | ||
| ARRHYTHMIA | 0/386 (0%) | 1/381 (0.3%) | ||
| ATRIAL FIBRILLATION | 1/386 (0.3%) | 0/381 (0%) | ||
| CARDIAC FAILURE CONGESTIVE | 0/386 (0%) | 1/381 (0.3%) | ||
| Ear and labyrinth disorders | ||||
| VERTIGO | 0/386 (0%) | 1/381 (0.3%) | ||
| VERTIGO POSITIONAL | 1/386 (0.3%) | 0/381 (0%) | ||
| Endocrine disorders | ||||
| ADRENAL INSUFFICIENCY | 1/386 (0.3%) | 0/381 (0%) | ||
| Eye disorders | ||||
| RETINOPATHY | 1/386 (0.3%) | 0/381 (0%) | ||
| Gastrointestinal disorders | ||||
| VOMITING | 11/386 (2.8%) | 18/381 (4.7%) | ||
| DIARRHOEA | 16/386 (4.1%) | 8/381 (2.1%) | ||
| NAUSEA | 7/386 (1.8%) | 12/381 (3.1%) | ||
| ABDOMINAL PAIN | 5/386 (1.3%) | 5/381 (1.3%) | ||
| GASTROINTESTINAL HAEMORRHAGE | 5/386 (1.3%) | 4/381 (1%) | ||
| GASTRIC PERFORATION | 7/386 (1.8%) | 0/381 (0%) | ||
| ABDOMINAL PAIN UPPER | 2/386 (0.5%) | 2/381 (0.5%) | ||
| DYSPHAGIA | 1/386 (0.3%) | 3/381 (0.8%) | ||
| STOMATITIS | 3/386 (0.8%) | 1/381 (0.3%) | ||
| UPPER GASTROINTESTINAL HAEMORRHAGE | 1/386 (0.3%) | 2/381 (0.5%) | ||
| GASTRIC HAEMORRHAGE | 0/386 (0%) | 2/381 (0.5%) | ||
| GASTROINTESTINAL OBSTRUCTION | 2/386 (0.5%) | 0/381 (0%) | ||
| GASTROINTESTINAL TOXICITY | 1/386 (0.3%) | 1/381 (0.3%) | ||
| ILEUS | 1/386 (0.3%) | 1/381 (0.3%) | ||
| OBSTRUCTION GASTRIC | 1/386 (0.3%) | 1/381 (0.3%) | ||
| SMALL INTESTINAL OBSTRUCTION | 2/386 (0.5%) | 0/381 (0%) | ||
| ABDOMINAL PAIN LOWER | 1/386 (0.3%) | 0/381 (0%) | ||
| ACUTE ABDOMEN | 0/386 (0%) | 1/381 (0.3%) | ||
| COLITIS | 1/386 (0.3%) | 0/381 (0%) | ||
| DUODENAL PERFORATION | 0/386 (0%) | 1/381 (0.3%) | ||
| ENTERITIS | 0/386 (0%) | 1/381 (0.3%) | ||
| ENTEROCOLITIS | 0/386 (0%) | 1/381 (0.3%) | ||
| ENTEROCUTANEOUS FISTULA | 1/386 (0.3%) | 0/381 (0%) | ||
| FOOD POISONING | 1/386 (0.3%) | 0/381 (0%) | ||
| GASTRIC STENOSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| GASTROINTESTINAL DISORDER | 1/386 (0.3%) | 0/381 (0%) | ||
| GASTROINTESTINAL PERFORATION | 1/386 (0.3%) | 0/381 (0%) | ||
| ILEAL PERFORATION | 1/386 (0.3%) | 0/381 (0%) | ||
| LARGE INTESTINAL ULCER | 1/386 (0.3%) | 0/381 (0%) | ||
| LARGE INTESTINE PERFORATION | 0/386 (0%) | 1/381 (0.3%) | ||
| MALLORY-WEISS SYNDROME | 0/386 (0%) | 1/381 (0.3%) | ||
| OESOPHAGEAL HAEMORRHAGE | 1/386 (0.3%) | 0/381 (0%) | ||
| PANCREATITIS ACUTE | 0/386 (0%) | 1/381 (0.3%) | ||
| General disorders | ||||
| ASTHENIA | 4/386 (1%) | 6/381 (1.6%) | ||
| FATIGUE | 5/386 (1.3%) | 3/381 (0.8%) | ||
| DEATH | 3/386 (0.8%) | 4/381 (1%) | ||
| PYREXIA | 4/386 (1%) | 3/381 (0.8%) | ||
| CHEST PAIN | 2/386 (0.5%) | 0/381 (0%) | ||
| ADVERSE DRUG REACTION | 0/386 (0%) | 1/381 (0.3%) | ||
| CATHETER THROMBOSIS | 0/386 (0%) | 1/381 (0.3%) | ||
| DISEASE PROGRESSION | 0/386 (0%) | 1/381 (0.3%) | ||
| GENERAL PHYSICAL HEALTH DETERIORATION | 0/386 (0%) | 1/381 (0.3%) | ||
| HYPERPYREXIA | 0/386 (0%) | 1/381 (0.3%) | ||
| MUCOSAL INFLAMMATION | 1/386 (0.3%) | 0/381 (0%) | ||
| MULTI-ORGAN FAILURE | 1/386 (0.3%) | 0/381 (0%) | ||
| DEVICE OCCLUSION | 1/386 (0.3%) | 0/381 (0%) | ||
| STENT MALFUNCTION | 1/386 (0.3%) | 0/381 (0%) | ||
| THROMBOSIS IN DEVICE | 1/386 (0.3%) | 0/381 (0%) | ||
| Hepatobiliary disorders | ||||
| HYPERBILIRUBINAEMIA | 0/386 (0%) | 4/381 (1%) | ||
| BILE DUCT STONE | 1/386 (0.3%) | 0/381 (0%) | ||
| CHOLECYSTITIS | 0/386 (0%) | 1/381 (0.3%) | ||
| JAUNDICE | 1/386 (0.3%) | 0/381 (0%) | ||
| LIVER DISORDER | 1/386 (0.3%) | 0/381 (0%) | ||
| BILE DUCT STENOSIS | 0/386 (0%) | 1/381 (0.3%) | ||
| CHOLANGITIS | 0/386 (0%) | 1/381 (0.3%) | ||
| Immune system disorders | ||||
| HYPERSENSITIVITY | 0/386 (0%) | 1/381 (0.3%) | ||
| Infections and infestations | ||||
| PERITONITIS | 1/386 (0.3%) | 1/381 (0.3%) | ||
| PNEUMONIA | 8/386 (2.1%) | 7/381 (1.8%) | ||
| SEPSIS | 4/386 (1%) | 1/381 (0.3%) | ||
| URINARY TRACT INFECTION | 3/386 (0.8%) | 1/381 (0.3%) | ||
| SEPTIC SHOCK | 1/386 (0.3%) | 2/381 (0.5%) | ||
| INFECTION | 2/386 (0.5%) | 0/381 (0%) | ||
| NEUTROPENIC INFECTION | 0/386 (0%) | 2/381 (0.5%) | ||
| PNEUMONIA BACTERIAL | 1/386 (0.3%) | 1/381 (0.3%) | ||
| APPENDICITIS | 0/386 (0%) | 1/381 (0.3%) | ||
| BACILLUS INFECTION | 0/386 (0%) | 1/381 (0.3%) | ||
| BACTERAEMIA | 0/386 (0%) | 1/381 (0.3%) | ||
| DEVICE RELATED INFECTION | 0/386 (0%) | 1/381 (0.3%) | ||
| ERYSIPELAS | 0/386 (0%) | 1/381 (0.3%) | ||
| GASTROENTERITIS VIRAL | 0/386 (0%) | 1/381 (0.3%) | ||
| LUNG ABSCESS | 0/386 (0%) | 1/381 (0.3%) | ||
| NEUTROPENIC SEPSIS | 0/386 (0%) | 1/381 (0.3%) | ||
| OSTEOMYELITIS CHRONIC | 1/386 (0.3%) | 0/381 (0%) | ||
| PERITONITIS BACTERIAL | 0/386 (0%) | 1/381 (0.3%) | ||
| PNEUMONIA PRIMARY ATYPICAL | 1/386 (0.3%) | 0/381 (0%) | ||
| TOOTH INFECTION | 1/386 (0.3%) | 0/381 (0%) | ||
| UROSEPSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| WOUND INFECTION | 1/386 (0.3%) | 0/381 (0%) | ||
| ATYPICAL PNEUMONIA | 1/386 (0.3%) | 0/381 (0%) | ||
| POST PROCEDURAL INFECTION | 1/386 (0.3%) | 0/381 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| AFFERENT LOOP SYNDROME | 0/386 (0%) | 1/381 (0.3%) | ||
| DEVICE MALFUNCTION | 1/386 (0.3%) | 0/381 (0%) | ||
| OESOPHAGEAL INJURY | 0/386 (0%) | 1/381 (0.3%) | ||
| PNEUMOTHORAX TRAUMATIC | 1/386 (0.3%) | 0/381 (0%) | ||
| POST PROCEDURAL HAEMORRHAGE | 1/386 (0.3%) | 0/381 (0%) | ||
| LACERATION | 0/386 (0%) | 1/381 (0.3%) | ||
| STENT OCCLUSION | 1/386 (0.3%) | 0/381 (0%) | ||
| WOUND DEHISCENCE | 1/386 (0.3%) | 0/381 (0%) | ||
| WRIST FRACTURE | 0/386 (0%) | 1/381 (0.3%) | ||
| STOMA SITE HAEMORRHAGE | 1/386 (0.3%) | 0/381 (0%) | ||
| Investigations | ||||
| BLOOD POTASSIUM DECREASED | 0/386 (0%) | 1/381 (0.3%) | ||
| BLOOD SODIUM DECREASED | 0/386 (0%) | 1/381 (0.3%) | ||
| Metabolism and nutrition disorders | ||||
| DECREASED APPETITE | 8/386 (2.1%) | 13/381 (3.4%) | ||
| DEHYDRATION | 7/386 (1.8%) | 3/381 (0.8%) | ||
| HYPOKALAEMIA | 2/386 (0.5%) | 7/381 (1.8%) | ||
| HYPERGLYCAEMIA | 1/386 (0.3%) | 1/381 (0.3%) | ||
| DIABETES MELLITUS | 0/386 (0%) | 1/381 (0.3%) | ||
| DIABETIC KETOACIDOSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| ELECTROLYTE IMBALANCE | 1/386 (0.3%) | 0/381 (0%) | ||
| HYPOCALCAEMIA | 1/386 (0.3%) | 0/381 (0%) | ||
| HYPOMAGNESAEMIA | 1/386 (0.3%) | 0/381 (0%) | ||
| HYPONATRAEMIA | 0/386 (0%) | 1/381 (0.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| FLANK PAIN | 1/386 (0.3%) | 0/381 (0%) | ||
| MUSCULAR WEAKNESS | 0/386 (0%) | 1/381 (0.3%) | ||
| PAIN IN EXTREMITY | 1/386 (0.3%) | 0/381 (0%) | ||
| ARTHRALGIA | 1/386 (0.3%) | 0/381 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| TUMOUR HAEMORRHAGE | 1/386 (0.3%) | 2/381 (0.5%) | ||
| BREAST CANCER | 1/386 (0.3%) | 0/381 (0%) | ||
| TUMOUR NECROSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| TUMOUR PERFORATION | 0/386 (0%) | 1/381 (0.3%) | ||
| Nervous system disorders | ||||
| CEREBRAL INFARCTION | 2/386 (0.5%) | 1/381 (0.3%) | ||
| CEREBROVASCULAR ACCIDENT | 1/386 (0.3%) | 2/381 (0.5%) | ||
| CONVULSION | 1/386 (0.3%) | 1/381 (0.3%) | ||
| POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME | 2/386 (0.5%) | 0/381 (0%) | ||
| CEREBRAL HAEMORRHAGE | 0/386 (0%) | 1/381 (0.3%) | ||
| ISCHAEMIC STROKE | 1/386 (0.3%) | 0/381 (0%) | ||
| LOSS OF CONSCIOUSNESS | 1/386 (0.3%) | 0/381 (0%) | ||
| NERVOUS SYSTEM DISORDER | 1/386 (0.3%) | 0/381 (0%) | ||
| VIITH NERVE PARALYSIS | 0/386 (0%) | 1/381 (0.3%) | ||
| Psychiatric disorders | ||||
| CONFUSIONAL STATE | 1/386 (0.3%) | 1/381 (0.3%) | ||
| DEPRESSION | 1/386 (0.3%) | 1/381 (0.3%) | ||
| ALCOHOL ABUSE | 1/386 (0.3%) | 0/381 (0%) | ||
| ANXIETY | 2/386 (0.5%) | 0/381 (0%) | ||
| COMPLETED SUICIDE | 1/386 (0.3%) | 0/381 (0%) | ||
| RESTLESSNESS | 1/386 (0.3%) | 0/381 (0%) | ||
| Renal and urinary disorders | ||||
| RENAL FAILURE | 4/386 (1%) | 3/381 (0.8%) | ||
| RENAL IMPAIRMENT | 2/386 (0.5%) | 1/381 (0.3%) | ||
| HYDRONEPHROSIS | 2/386 (0.5%) | 0/381 (0%) | ||
| NEPHROPATHY TOXIC | 0/386 (0%) | 1/381 (0.3%) | ||
| RENAL FAILURE ACUTE | 0/386 (0%) | 1/381 (0.3%) | ||
| RENAL SALT-WASTING SYNDROME | 0/386 (0%) | 1/381 (0.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| PULMONARY EMBOLISM | 8/386 (2.1%) | 13/381 (3.4%) | ||
| PNEUMONIA ASPIRATION | 0/386 (0%) | 3/381 (0.8%) | ||
| DYSPNOEA | 0/386 (0%) | 2/381 (0.5%) | ||
| PULMONARY ARTERY THROMBOSIS | 0/386 (0%) | 2/381 (0.5%) | ||
| RESPIRATORY FAILURE | 0/386 (0%) | 1/381 (0.3%) | ||
| HAEMOPTYSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| INTERSTITIAL LUNG DISEASE | 1/386 (0.3%) | 0/381 (0%) | ||
| PHARYNGEAL INFLAMMATION | 1/386 (0.3%) | 0/381 (0%) | ||
| PLEURAL EFFUSION | 1/386 (0.3%) | 0/381 (0%) | ||
| PNEUMONITIS | 0/386 (0%) | 1/381 (0.3%) | ||
| PNEUMOTHORAX | 2/386 (0.5%) | 0/381 (0%) | ||
| PULMONARY HAEMORRHAGE | 1/386 (0.3%) | 0/381 (0%) | ||
| PULMONARY OEDEMA | 1/386 (0.3%) | 0/381 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME | 0/386 (0%) | 1/381 (0.3%) | ||
| PEMPHIGOID | 0/386 (0%) | 1/381 (0.3%) | ||
| Vascular disorders | ||||
| DEEP VEIN THROMBOSIS | 3/386 (0.8%) | 4/381 (1%) | ||
| HYPERTENSION | 1/386 (0.3%) | 1/381 (0.3%) | ||
| VENOUS THROMBOSIS | 1/386 (0.3%) | 1/381 (0.3%) | ||
| ARTERIAL THROMBOSIS LIMB | 0/386 (0%) | 1/381 (0.3%) | ||
| HAEMORRHAGE | 1/386 (0.3%) | 0/381 (0%) | ||
| HYPOTENSION | 0/386 (0%) | 1/381 (0.3%) | ||
| HYPOVOLAEMIC SHOCK | 1/386 (0.3%) | 0/381 (0%) | ||
| JUGULAR VEIN THROMBOSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| PERIPHERAL ISCHAEMIA | 1/386 (0.3%) | 0/381 (0%) | ||
| THROMBOSIS | 1/386 (0.3%) | 0/381 (0%) | ||
| VASOSPASM | 0/386 (0%) | 1/381 (0.3%) | ||
| VENOUS THROMBOSIS LIMB | 0/386 (0%) | 1/381 (0.3%) | ||
| EMBOLISM | 0/386 (0%) | 1/381 (0.3%) | ||
| PERIPHERAL ARTERY THROMBOSIS | 0/386 (0%) | 1/381 (0.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Bevacizumab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 378/386 (97.9%) | 373/381 (97.9%) | ||
| Blood and lymphatic system disorders | ||||
| NEUTROPENIA | 250/386 (64.8%) | 221/381 (58%) | ||
| ANAEMIA | 83/386 (21.5%) | 111/381 (29.1%) | ||
| THROMBOCYTOPENIA | 70/386 (18.1%) | 67/381 (17.6%) | ||
| LEUKOPENIA | 21/386 (5.4%) | 18/381 (4.7%) | ||
| Gastrointestinal disorders | ||||
| NAUSEA | 264/386 (68.4%) | 248/381 (65.1%) | ||
| VOMITING | 192/386 (49.7%) | 188/381 (49.3%) | ||
| DIARRHOEA | 180/386 (46.6%) | 142/381 (37.3%) | ||
| CONSTIPATION | 141/386 (36.5%) | 124/381 (32.5%) | ||
| STOMATITIS | 111/386 (28.8%) | 88/381 (23.1%) | ||
| ABDOMINAL PAIN | 82/386 (21.2%) | 55/381 (14.4%) | ||
| ABDOMINAL PAIN UPPER | 39/386 (10.1%) | 32/381 (8.4%) | ||
| DYSPEPSIA | 23/386 (6%) | 16/381 (4.2%) | ||
| General disorders | ||||
| FATIGUE | 157/386 (40.7%) | 145/381 (38.1%) | ||
| ASTHENIA | 77/386 (19.9%) | 64/381 (16.8%) | ||
| PYREXIA | 54/386 (14%) | 51/381 (13.4%) | ||
| MUCOSAL INFLAMMATION | 53/386 (13.7%) | 32/381 (8.4%) | ||
| OEDEMA PERIPHERAL | 30/386 (7.8%) | 37/381 (9.7%) | ||
| Infections and infestations | ||||
| GINGIVITIS | 25/386 (6.5%) | 7/381 (1.8%) | ||
| NASOPHARYNGITIS | 26/386 (6.7%) | 15/381 (3.9%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 24/386 (6.2%) | 14/381 (3.7%) | ||
| Investigations | ||||
| CREATININE RENAL CLEARANCE DECREASED | 49/386 (12.7%) | 63/381 (16.5%) | ||
| WEIGHT DECREASED | 44/386 (11.4%) | 43/381 (11.3%) | ||
| Metabolism and nutrition disorders | ||||
| DECREASED APPETITE | 204/386 (52.8%) | 175/381 (45.9%) | ||
| HYPOKALAEMIA | 17/386 (4.4%) | 18/381 (4.7%) | ||
| DEHYDRATION | 19/386 (4.9%) | 11/381 (2.9%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| BACK PAIN | 29/386 (7.5%) | 21/381 (5.5%) | ||
| PAIN IN EXTREMITY | 21/386 (5.4%) | 7/381 (1.8%) | ||
| MYALGIA | 19/386 (4.9%) | 20/381 (5.2%) | ||
| Nervous system disorders | ||||
| PERIPHERAL SENSORY NEUROPATHY | 55/386 (14.2%) | 50/381 (13.1%) | ||
| HEADACHE | 51/386 (13.2%) | 36/381 (9.4%) | ||
| NEUROPATHY PERIPHERAL | 42/386 (10.9%) | 41/381 (10.8%) | ||
| DYSGEUSIA | 42/386 (10.9%) | 39/381 (10.2%) | ||
| DIZZINESS | 38/386 (9.8%) | 41/381 (10.8%) | ||
| Psychiatric disorders | ||||
| INSOMNIA | 43/386 (11.1%) | 37/381 (9.7%) | ||
| Renal and urinary disorders | ||||
| PROTEINURIA | 28/386 (7.3%) | 20/381 (5.2%) | ||
| RENAL IMPAIRMENT | 24/386 (6.2%) | 21/381 (5.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| HICCUPS | 52/386 (13.5%) | 56/381 (14.7%) | ||
| EPISTAXIS | 64/386 (16.6%) | 20/381 (5.2%) | ||
| DYSPNOEA | 18/386 (4.7%) | 25/381 (6.6%) | ||
| COUGH | 15/386 (3.9%) | 22/381 (5.8%) | ||
| Skin and subcutaneous tissue disorders | ||||
| PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME | 183/386 (47.4%) | 124/381 (32.5%) | ||
| ALOPECIA | 94/386 (24.4%) | 87/381 (22.8%) | ||
| SKIN HYPERPIGMENTATION | 56/386 (14.5%) | 53/381 (13.9%) | ||
| RASH | 39/386 (10.1%) | 32/381 (8.4%) | ||
| PIGMENTATION DISORDER | 27/386 (7%) | 13/381 (3.4%) | ||
| NAIL DISORDER | 22/386 (5.7%) | 13/381 (3.4%) | ||
| Vascular disorders | ||||
| HYPERTENSION | 84/386 (21.8%) | 51/381 (13.4%) | ||
Limitations/Caveats
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 | Hoffman-LaRoche |
| Phone | 800-821-8590 |
- AVF4200g
- BO20904