A Study of Bevacizumab With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma

Melanoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00434252
• Other study ID #: AVF4096g
• Status: Completed
• Phase: Phase 2
• First received: February 11, 2007
• Last updated: August 22, 2011
• Start date: February 2007

Study information

• Verified date: August 2011
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• bevacizumab
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)
• carboplatin
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
• paclitaxel
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)
• placebo
Administered by IV infusion on the first day of each 3-week cycle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	No
Secondary	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.	Up to 102 weeks	No
Secondary	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.	Up to 102 weeks	No
Secondary	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.	Up to 102 weeks	No
Secondary	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.	Up to 102 weeks	No
Secondary	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.	6 months	No
Secondary	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.	24 weeks	No
Secondary	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.	Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination.	No