Temozolomide and Bevacizumab in Treating Patients With Metastatic Melanoma of the Eye

August 23, 2013 updated by: Institut Curie

Phase II Single-Center Study of Bevacizumab in Combination With Temozolomide in Patients With First-Line Metastatic Uveal Melanoma

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temozolomide together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying giving temozolomide together with bevacizumab to see how well they work in treating patients with metastatic melanoma of the eye.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the efficacy of temozolomide in combination with bevacizumab in treating patients with metastatic uveal melanoma not amenable to curative surgery.

Secondary

  • To determine response rate in these patients.
  • To determine duration of response in these patients.
  • To determine progression-free survival of these patients.
  • To determine overall survival of these patients.
  • To determine the safety of treatment with this regimen in these patients.
  • To study the CT perfusion imaging for functional imaging of response in these patients.
  • To determine the pharmacogenetic influence of constitutional VEGF-A polymorphism on the efficacy and toxicity of bevacizumab. (ancillary)

OUTLINE: Patients receive oral temozolomide once daily on days 1-7 and 15-21 and bevacizumab IV over 30-90 minutes on days 8 and 22. Treatment repeats every 28 days for up to 6 courses. Patients achieving at least stable disease then receive bevacizumab monotherapy IV every 2 weeks as maintenance therapy in the absence of unacceptable toxicity and disease progression. Patients undergo CT perfusion imaging at baseline, day 28, and at 3 and 6 months.

Blood samples are collected at baseline and then periodically for VEGF-A genetic polymorphism analysis.

After completion of study treatment, patients are followed up at 1 month.

Study Type

Interventional

Enrollment (Anticipated)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed uveal melanoma

    • Metastatic disease
  • Measurable disease, defined as ≥ 1 measurable lesion as measured by RECIST criteria
  • No curative surgical treatment envisaged
  • No active brain metastases (if clinical suspicion, must have a brain CT scan within 28 days)

PATIENT CHARACTERISTICS:

  • WHO performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • Life expectancy ≥ 12 weeks
  • Hemoglobin ≥ 10 g/dL
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR calculated creatinine clearance ≥ 50 mL/min
  • Proteinuria < 2+ on urinary dipstick OR 24-hour proteinuria ≤ 1 g
  • Total bilirubin ≤ 1.5 times ULN
  • AST/ALT ≤ 2.5 times ULN
  • Lactate dehydrogenase ≤ 5 times ULN
  • INR and PT ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • No uncontrolled active disease or at risk of bleeding, ongoing infection, or clotting disorder
  • No other cancer except for skin carcinomas and cervical carcinoma in situ
  • No pre-existing peripheral neuropathy, > grade 2 (NCI CTC-AE)
  • No failure to comply with the medical follow-up of the study for geographical, social, or psychological reasons
  • No recent thrombophlebitis or pulmonary embolism within the past 6 months
  • No uncontrolled hypertension (systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg)

  • No concurrent active cardiovascular disease, uncontrolled by medical treatment within the past 6 months, including any of the following:

    • Unstable angina
    • Severe hypertension
    • Severe arrhythmia
  • No unhealed wound, active peptic ulcer, bone fracture, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No known hypersensitivity to bevacizumab, temozolomide, or their excipients

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy for metastatic disease
  • At least 24 hours since insertion of central infusion port
  • More than 5 days since prior non-hepatic biopsy or aspiration cytology
  • More than 10 days since prior aspirin (> 325 mg/day), clopidogrel (> 75 mg/day), or full-dose oral or parenteral anticoagulant therapy, except prophylactic anticoagulant therapy prior to inclusion in the study
  • More than 14 days since prior laparoscopic liver biopsy
  • More than 28 days since prior major surgery
  • More than 28 days since prior participation in another study with experimental treatment
  • No other concurrent anticancer treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease control rate, in terms of objective response rate and the stable disease rate determined according to RECIST criteria at 6 months

Secondary Outcome Measures

Outcome Measure
Response rate
Progression-free survival
Overall survival
Duration of response
Safety of this regimen in these patients
Functional imaging of response by CT perfusion imaging

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Curie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (ANTICIPATED)

October 1, 2012

Study Registration Dates

First Submitted

October 7, 2010

First Submitted That Met QC Criteria

October 7, 2010

First Posted (ESTIMATE)

October 8, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

August 26, 2013

Last Update Submitted That Met QC Criteria

August 23, 2013

Last Verified

August 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000683852
  • CLCC-IC-2009-01
  • EUDRACT-2009-011751-46
  • EU-21063

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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