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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01217398
First received: October 7, 2010
Last updated: August 23, 2013
Last verified: August 2012
  Purpose

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 Intervention Phase
Intraocular Melanoma
Biological: bevacizumab
Drug: temozolomide
Genetic: polymorphism analysis
Other: pharmacogenomic studies
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Safety of this regimen in these patients [ Designated as safety issue: Yes ]
  • Functional imaging of response by CT perfusion imaging [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: October 2009
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217398

Locations
France
Institut Curie Hopital Recruiting
Paris, France, 75248
Contact: Contact Person    33-1-4432-4068    sophie.piperno-neumann@curie.net   
Sponsors and Collaborators
Institut Curie
Investigators
Principal Investigator: Sophie Piperno-Neumann, MD Institut Curie
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01217398     History of Changes
Other Study ID Numbers: CDR0000683852, CLCC-IC-2009-01, EUDRACT-2009-011751-46, EU-21063
Study First Received: October 7, 2010
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
ciliary body and choroid melanoma, medium/large size
ciliary body and choroid melanoma, small size
iris melanoma
metastatic intraocular melanoma
stage IV intraocular melanoma

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Temozolomide
Dacarbazine
Bevacizumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014