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

Primary Purpose

Intraocular Melanoma

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
bevacizumab
temozolomide
polymorphism analysis
pharmacogenomic studies
Sponsored by
Institut Curie
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intraocular Melanoma focused on measuring ciliary body and choroid melanoma, medium/large size, ciliary body and choroid melanoma, small size, iris melanoma, metastatic intraocular melanoma, stage IV intraocular melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut Curie HopitalRecruiting

Outcomes

Primary Outcome Measures

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

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

Full Information

First Posted
October 7, 2010
Last Updated
August 23, 2013
Sponsor
Institut Curie
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1. Study Identification

Unique Protocol Identification Number
NCT01217398
Brief Title
Temozolomide and Bevacizumab in Treating Patients With Metastatic Melanoma of the Eye
Official Title
Phase II Single-Center Study of Bevacizumab in Combination With Temozolomide in Patients With First-Line Metastatic Uveal Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Unknown status
Study Start Date
October 2009 (undefined)
Primary Completion Date
October 2012 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Institut Curie

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intraocular Melanoma
Keywords
ciliary body and choroid melanoma, medium/large size, ciliary body and choroid melanoma, small size, iris melanoma, metastatic intraocular melanoma, stage IV intraocular melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Type
Drug
Intervention Name(s)
temozolomide
Intervention Type
Genetic
Intervention Name(s)
polymorphism analysis
Intervention Type
Other
Intervention Name(s)
pharmacogenomic studies
Primary Outcome Measure Information:
Title
Disease control rate, in terms of objective response rate and the stable disease rate determined according to RECIST criteria at 6 months
Secondary Outcome Measure Information:
Title
Response rate
Title
Duration of response
Title
Progression-free survival
Title
Overall survival
Title
Safety of this regimen in these patients
Title
Functional imaging of response by CT perfusion imaging

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sophie Piperno-Neumann, MD
Organizational Affiliation
Institut Curie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Curie Hopital
City
Paris
ZIP/Postal Code
75248
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
33-1-4432-4068
Email
sophie.piperno-neumann@curie.net

12. IPD Sharing Statement

Learn more about this trial

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

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