A Study of Avastin (Bevacizumab) in Combination With Fotemustine in Patients With Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01069627
First received: December 15, 2009
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Malignant Melanoma
Drug: bevacizumab [Avastin]
Drug: fotemustine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study to Assess the Anti-tumor Activity of Avastin in Combination With Fotemustine as First-line Therapy in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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:
  • Time to Progression (TTP) - Percentage of Participants With an Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.

  • TTP - Time to Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 - Percentage of Participants With an Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 CR - Time to Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 Overall Response of CR or PR - Percentage of Participants With an Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Overall Response of CR or PR - Time to Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Stable Disease - Percentage of Participants With an Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Stable Disease - Time to Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months) ] [ Designated as safety issue: No ]
    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.

  • OS - Time to Event [ Time Frame: Baseline, every 3 weeks to end-of-treatment, every 3 months during follow-up, to death or end-of-study (maximum of 36 months) ] [ Designated as safety issue: No ]
    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 Treatment Failure (TTF) - Percentage of Participants With an Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.

  • Time to CR - Percentage of Participants With an Event [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 9 weeks during study treatment, and every 3 months during follow-up, up to 36 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 20
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
15 mg/kg intravenously on day 1 of every 3 week cycle
Drug: fotemustine
100 mg/m² intravenously on Days 1, 8, and 15, followed by 4 weeks of rest, then every 21 days up to 4 to 6 cycles

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • cutaneous malignant melanoma;
  • advanced, inoperable stage IV melanoma;
  • measurable and/or evaluable sites of metastases.

Exclusion Criteria:

  • 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.
  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: NCT01069627

Locations
Italy
Firenze, Italy, 50100
Genova, Italy, 16132
Milano, Italy, 20133
Torino, Italy, 10126
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Disclosures Group, Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01069627     History of Changes
Other Study ID Numbers: ML19309
Study First Received: December 15, 2009
Results First Received: May 23, 2014
Last Updated: May 23, 2014
Health Authority: Italy: Ministero della Salute

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
Fotemustine
Bevacizumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014