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
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
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
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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