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

Intraocular Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01217398
• Other study ID #: CDR0000683852
• Secondary ID: CLCC-IC-2009-01E
• Status: Recruiting
• Phase: Phase 2
• First received: October 7, 2010
• Last updated: August 23, 2013
• Start date: October 2009

Study information

• Verified date: August 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Intraocular Melanoma
• Melanoma
• Uveal Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• temozolomide

Genetic:
• polymorphism analysis

Other:
• pharmacogenomic studies

Locations

Country	Name	City	State
France	Institut Curie Hopital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut Curie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease control rate, in terms of objective response rate and the stable disease rate determined according to RECIST criteria at 6 months			No
Secondary	Response rate			No
Secondary	Duration of response			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No
Secondary	Safety of this regimen in these patients			Yes
Secondary	Functional imaging of response by CT perfusion imaging			No