A Study of Avastin (Bevacizumab) in Combination With Fotemustine in Patients With Metastatic Melanoma
- Conditions
- Malignant Melanoma
- Interventions
- Registration Number
- NCT01069627
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will investigate the efficacy and safety of bevacizumab + fotemustine in patients with stage IV melanoma, previously untreated with chemo- or immunotherapy for metastatic disease. Patients will receive Avastin (15mg/kg intravenously\[IV\]) on Day 1 of every 3 week cycle, in combination with fotemustine (100mg/m² IV) on Days 1, 8 and 15, followed by 4 weeks rest, followed by 100mg/m² IV every 3 weeks for 4-6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is \<100 individuals.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- cutaneous malignant melanoma;
- advanced, inoperable stage IV melanoma;
- measurable and/or evaluable sites of metastases.
- prior chemotherapy and/or IFN/IL2 based immunotherapy for metastatic disease;
- prior malignancies within past 5 years, with the exception of cured non-melanoma skin cancer, or in situ cancer of cervix;
- clinically significant cardiovascular disease;
- ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 bevacizumab [Avastin] - 1 fotemustine -
- Primary Outcome Measures
Name Time Method Percentage of Participants With Complete Response (CR) or Partial Response (PR) Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The percentage of participants with an objective response, defined as achieving CR or PR, as evaluated by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target), PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Percentage of Participants With Clinical Benefit of CR, PR, or Stable Disease (SD) Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The percentage of participants with an objective response of CR, PR, or SD, as evaluated by RECIST criteria. CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target), PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for pregressive disease (PD). The clinical benefit was finally assessed by computing absolute frequencies and percentages participants with best overall tumor response equal to CR, PR, or SD.
- Secondary Outcome Measures
Name Time Method Duration of CR - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months Evaluated only for participants whose best overall response was CR. The start date was the date of first documented CR and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up.
Duration of Overall Response of CR or PR - Time to Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The start date was the date of first documented CR or PR and the end date was defined as the date of first documented progression of disease. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up. Median duration of CR or PR was estimated using the Kaplan-Meier method.
Overall Survival (OS) - Percentage of Participants With an Event Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months) OS was defined as the time from the starting day of the therapy up to death or the last date the participant was known to be alive.
Time to Progression (TTP) - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months TTP was defined as the time in days from the date of first study treatment until the date of tumor progression or death. Failure events were defined as occurrence of death or progression of disease. Data for participants who were alive without tumor progression at the end of the study were censured at the end of the observation period.
Duration of Overall Response of CR or PR - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The start date was the date of first documented CR or PR and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up.
TTP - Time to Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months TTP was defined as the time in days from the of first study treatment until the date of tumor progression or death. Failure events were defined as occurrence of death or progression of disease. Data for participants who were alive without tumor progression at the end of the study were censored at the end of the observation period. Median TTP was estimated using the Kaplan-Meier method.
Duration of CR - Time to Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The start date was the date of first documented CR and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up. Median duration of CR was estimated using the Kaplan-Meier method.
Duration of Stable Disease - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months Stable disease was defined as achieving CR, PR, or SD. The start date was the date of first documented CR, PR, or SD and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up.
Time to Treatment Failure (TTF) - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The time from date of start of treatment to the earliest among date of progression, date of death due to any cause, or date of discontinuation due to reason other than 'Protocol Violation' or 'Administrative Problem'. For the participants who did not experience treatment failure, TTF was censored at last adequate tumour assessment.
TTF - Time to Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The time from date of start of treatment to the earliest among date of progression, date of death due to any cause, or date of discontinuation due to reason other than 'Protocol Violation' or 'Administrative Problem'. For the participants who did not experience treatment failure, TTF was censored at last adequate tumour assessment. Median TTF was estimated using the Kaplan-Meier method.
Duration of Stable Disease - Time to Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months Stable disease was defined as achieving CR, PR, or SD. The start date was the date of first documented CR, PR, or SD and the end date was defined as the date of first documented progression of disease, or death. Participants who did not experience progression of disease were censored at last tumor assessment date or at maximum follow-up. Median duration of CR, PR, or SD was estimated using the Kaplan-Meier method.
OS - Time to Event Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months) The time from the starting day of the therapy up to death or the last date the participant was known to be alive. Median OS was estimated using the Kaplan-Meier method.
Time to CR - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The time between date of start of treatment until first documented CR. This analysis included all responders. Participants who did not achieve a confirmed CR were censored at last adequate tumour assessment date or at maximum follow-up.
Time to CR - Time To Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The time between date of start of treatment until first documented CR. This analysis included all responders. Participants who did not achieve a confirmed CR were censored at last adequate tumour assessment date or at maximum follow-up. Mean time to CR was estimated using the Kaplan-Meier method.
Time to Overall Response of CR or PR - Percentage of Participants With an Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The time between date of start of treatment until first documented response of CR or PR. This analysis included all responders. Participants who did not achieve a confirmed CR or PR were censored at last adequate tumour assessment date or at maximum follow-up.
Time to Overall Response of CR or PR - Time to Event Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months The time between date of start of treatment until first documented response of CR or PR. This analysis included all responders. Participants who did not achieve a confirmed CR or PR were censored at last adequate tumor assessment date or at maximum follow-up. Mean time to CR or PR was estimated using the Kaplan-Meier method.