Back to resultsA Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma (BEAM)
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
bevacizumab
carboplatin
paclitaxel
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Avastin, BEAM, Metastatic melanoma
Eligibility Criteria
Inclusion Criteria:
- Signed Informed Consent Form
- Age ≥ 18 years
- Metastatic melanoma (Stage IV)
- Histologically confirmed malignant melanoma with measurable or non-measurable disease
- Ability and willingness to comply with study and follow-up procedures
Exclusion Criteria:
- Prior treatment for Stage IV disease with chemotherapy or biologic therapy such as interferon and interleukin-2
- Complete surgical resection or irradiation of all identifiable sites of disease at randomization
- Radiation therapy within 14 days prior to Day 1
- Prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial growth factor (VEGF) pathway-targeted therapy
- Melanoma of ocular origin
- Known central nervous system (CNS) disease/brain metastases (history of brain disease or active disease)
- Life expectancy of < 12 weeks
- Current, recent, or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
- Inadequate organ function
- History of other malignancies within 5 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
- Inadequately controlled hypertension
- History of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Class II or greater CHF
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
- History of hemoptysis within 1 month prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Known hypersensitivity to any component of bevacizumab
- Pregnancy (positive pregnancy test) or lactation
- Current, ongoing treatment with full-dose warfarin
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Carboplatin+Paclitaxel+Placebo
Carboplatin+Paclitaxel+Bevacizumab
Arm Description
Outcomes
Primary Outcome Measures
Progression-free Survival
Progression-free survival (PFS) was defined as the time from randomization to documented disease progression (at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions) or death on study (death from any cause occurring no later than 30 days after last dose of any study treatment), whichever occurred first, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST). Median PFS was estimated using the Kaplan-Meier method.
Secondary Outcome Measures
Overall Survival (OS)
Overall survival was defined as the time from randomization to death from any cause. Median OS was estimated using the Kaplan-Meier method. For patients without documentation of death, overall survival will be censored at the time of the last known contact.
Number of Participants With Objective Response
Objective response was assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and was inclusive of complete and partial response determined on two consecutive investigator assessments conducted ≥ 4 weeks apart.
Percentage of Participants With an Objective Response
Objective response was defined as a complete or partial response according to RECIST criteria as assessed by the investigator on two consecutive assessments conducted at least 4 weeks apart.
The 95% Confidence Interval (CI) was calculated using the normal approximation to the binomial distribution.
Duration of Objective Response
Duration of objective response was defined as the time from the initial objective response to documented disease progression or death, whichever occurred first, assessed by the investigator using RECIST. Progressive disease was defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Duration of response was estimated using the Kaplan-Meier method.
Six-month Landmark Survival Rate
Six-month Landmark Survival Rate was defined as the percentage of participants surviving at 6 months following randomization. Overall Survival was estimated using the Kaplan-Meier method.
Twenty-Four Week Landmark Stable Disease
As assessed by the investigator using RECIST and defined as the absence of disease progression for 24 weeks from the time of randomization.
The percentage of patients who did not experience disease progression or death at 24 weeks following randomization was estimated using Kaplan-Meier methodology. If no tumor assessments were performed after the baseline visit, the patient will be censored at the date of randomization plus 1 day.
Number of Participants With Select Adverse Events
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Select adverse events included arterial thromboembolic events (any grade), bleeding other than pulmonary or central nervous system (CNS) bleeding (Grade >= 3), CNS bleeding (any grade), febrile neutropenia (any grade), hypertension (Grade >= 3), neutropenia (Grade >= 3), pulmonary bleeding (any grade) and wound dehiscence (Grade >= 3).
*All serious adverse events are listed in the Adverse Event Reporting section.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00434252
Brief Title
A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma
Acronym
BEAM
Official Title
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
February 2007 (Actual)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
Brief Summary
This Phase II, multicenter, randomized, double-blind, placebo-controlled trial was designed to estimate the efficacy and characterize the safety of bevacizumab when combined with carboplatin + paclitaxel chemotherapy compared with carboplatin + paclitaxel chemotherapy alone in patients with previously untreated metastatic melanoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Avastin, BEAM, Metastatic melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
214 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carboplatin+Paclitaxel+Placebo
Arm Type
Placebo Comparator
Arm Title
Carboplatin+Paclitaxel+Bevacizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Intervention Description
15 mg/kg by intravenous (IV) infusion on the first day of each 3-week cycle (dose was based on patient's weight at screening and remained the same throughout study)
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
Dose based on patients' creatinine clearance (Calvert formula) and administered by intravenous (IV) infusion on the first day of each 3-week cycle, for a maximum of 10 cycles
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
175 mg/m^2 by IV infusion on the first day of each 3-week cycle (dose was based on patient's weight and could be adjusted for weight change)
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Administered by IV infusion on the first day of each 3-week cycle
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression-free survival (PFS) was defined as the time from randomization to documented disease progression (at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions) or death on study (death from any cause occurring no later than 30 days after last dose of any study treatment), whichever occurred first, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST). Median PFS was estimated using the Kaplan-Meier method.
Time Frame
From randomization up to102 weeks. As of the clinical cut-off date (April 2009), the maximum time on treatment was 88 weeks, median time was 12.4 weeks for the Placebo arm and 16.1 weeks for the bevacizumab arm.
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival was defined as the time from randomization to death from any cause. Median OS was estimated using the Kaplan-Meier method. For patients without documentation of death, overall survival will be censored at the time of the last known contact.
Time Frame
Up to 102 weeks
Title
Number of Participants With Objective Response
Description
Objective response was assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and was inclusive of complete and partial response determined on two consecutive investigator assessments conducted ≥ 4 weeks apart.
Time Frame
Up to 102 weeks
Title
Percentage of Participants With an Objective Response
Description
Objective response was defined as a complete or partial response according to RECIST criteria as assessed by the investigator on two consecutive assessments conducted at least 4 weeks apart.
The 95% Confidence Interval (CI) was calculated using the normal approximation to the binomial distribution.
Time Frame
Up to 102 weeks
Title
Duration of Objective Response
Description
Duration of objective response was defined as the time from the initial objective response to documented disease progression or death, whichever occurred first, assessed by the investigator using RECIST. Progressive disease was defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Duration of response was estimated using the Kaplan-Meier method.
Time Frame
Up to 102 weeks
Title
Six-month Landmark Survival Rate
Description
Six-month Landmark Survival Rate was defined as the percentage of participants surviving at 6 months following randomization. Overall Survival was estimated using the Kaplan-Meier method.
Time Frame
6 months
Title
Twenty-Four Week Landmark Stable Disease
Description
As assessed by the investigator using RECIST and defined as the absence of disease progression for 24 weeks from the time of randomization.
The percentage of patients who did not experience disease progression or death at 24 weeks following randomization was estimated using Kaplan-Meier methodology. If no tumor assessments were performed after the baseline visit, the patient will be censored at the date of randomization plus 1 day.
Time Frame
24 weeks
Title
Number of Participants With Select Adverse Events
Description
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Select adverse events included arterial thromboembolic events (any grade), bleeding other than pulmonary or central nervous system (CNS) bleeding (Grade >= 3), CNS bleeding (any grade), febrile neutropenia (any grade), hypertension (Grade >= 3), neutropenia (Grade >= 3), pulmonary bleeding (any grade) and wound dehiscence (Grade >= 3).
*All serious adverse events are listed in the Adverse Event Reporting section.
Time Frame
Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed Informed Consent Form
Age ≥ 18 years
Metastatic melanoma (Stage IV)
Histologically confirmed malignant melanoma with measurable or non-measurable disease
Ability and willingness to comply with study and follow-up procedures
Exclusion Criteria:
Prior treatment for Stage IV disease with chemotherapy or biologic therapy such as interferon and interleukin-2
Complete surgical resection or irradiation of all identifiable sites of disease at randomization
Radiation therapy within 14 days prior to Day 1
Prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial growth factor (VEGF) pathway-targeted therapy
Melanoma of ocular origin
Known central nervous system (CNS) disease/brain metastases (history of brain disease or active disease)
Life expectancy of < 12 weeks
Current, recent, or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
Inadequate organ function
History of other malignancies within 5 years of Day 1, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
Inadequately controlled hypertension
History of hypertensive crisis or hypertensive encephalopathy
New York Heart Association (NYHA) Class II or greater CHF
History of myocardial infarction or unstable angina within 6 months prior to Day 1
History of stroke or transient ischemic attack within 6 months prior to Day 1
Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 1
History of hemoptysis within 1 month prior to Day 1
Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
Serious, non-healing wound, active ulcer, or untreated bone fracture
Known hypersensitivity to any component of bevacizumab
Pregnancy (positive pregnancy test) or lactation
Current, ongoing treatment with full-dose warfarin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Schwartz, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma
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