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

This study has been completed.
Sponsor:
Information provided by:
Genentech
ClinicalTrials.gov Identifier:
NCT00434252
First received: February 11, 2007
Last updated: August 22, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: bevacizumab
Drug: carboplatin
Drug: paclitaxel
Drug: placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Progression-free Survival [ 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. ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 102 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 102 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 102 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 102 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination. ] [ Designated as safety issue: No ]

    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.



Enrollment: 214
Study Start Date: February 2007
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Carboplatin+Paclitaxel+Placebo Drug: 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
Drug: 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)
Drug: placebo
Administered by IV infusion on the first day of each 3-week cycle
Experimental: Carboplatin+Paclitaxel+Bevacizumab 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)
Drug: 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
Drug: 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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00434252

Sponsors and Collaborators
Genentech
Investigators
Study Director: Richard Schwartz, M.D. Genentech
  More Information

No publications provided

Responsible Party: Disclosures Group, Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00434252     History of Changes
Other Study ID Numbers: AVF4096g
Study First Received: February 11, 2007
Results First Received: March 29, 2011
Last Updated: August 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
Avastin
BEAM
Metastatic melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Paclitaxel
Bevacizumab
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014