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

Sponsor

Institut Curie (Other)

Overall Status

Unknown status

CT.gov ID

NCT01217398

Collaborator

(none)

Enrollment

Location

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma	Biological: bevacizumab Drug: temozolomide Genetic: polymorphism analysis Other: pharmacogenomic studies	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2009

Anticipated Primary Completion Date :

Oct 1, 2012

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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