Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Temozolomide and Thalidomide in Treating Patients With Brain Metastases Secondary to Melanoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	CALGB-500102 NCT00072163

Objectives

Primary

1. Determine the objective response rate in patients with brain metastases secondary to melanoma treated with temozolomide and thalidomide.

Secondary

1. Determine the toxic effects of and tolerance to this regimen in these patients.
2. Determine the objective response rate in extracranial metastases of patients treated with this regimen.
3. Determine the time to first disease progression (intra- or extracranial) in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed metastatic melanoma
• Clinical evidence of brain metastases
  • At least 1 unidimensionally measurable brain lesion at least 2.0 cm by conventional techniques OR at least 1.0 cm by spiral CT scan or MRI
    • The following lesions are not considered measurable:
      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Lymphangitis cutis/pulmonis
      • Abdominal masses that are not confirmed and followed by imaging techniques
      • Cystic lesions
      • Lesions situated in a previously irradiated area, unless new growth is documented

Prior/Concurrent Therapy:

Biologic therapy

• At least 4 weeks since prior cytokines
  • Biologic agents used as adjuvants, vaccines, and cellular therapies do not require a 4-week washout period
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• No more than 1 prior chemotherapy regimen
• No prior chemotherapy for brain metastases
• No prior continuous daily temozolomide
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except steroids and hormones administered for non-disease-related conditions (e.g., insulin for diabetes) or for control of intracranial edema from brain metastases

Radiotherapy

• See Disease Characteristics
• Prior whole brain radiotherapy (WBRT) allowed provided patient has progressive disease in a measurable CNS lesion
• Prior stereotactic radiotherapy allowed provided patient has progressive disease in a measurable CNS lesion
• At least 4 weeks since prior WBRT
• At least 3 weeks since prior stereotactic radiosurgery
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior surgical resection

Other

• No concurrent warfarin or heparin products or their derivatives
• No concurrent antiplatelet therapy (e.g., daily aspirin, ibuprofen, or clopidogrel bisulfate)
• No concurrent bisphosphonates (e.g., zoledronate)

Patient Characteristics:

Age

• 18 and over

Performance status

• CTC 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• AST and ALT no greater than 2.5 times upper limit of normal (ULN)
• Lactic dehydrogenase no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2 mg/dL

Cardiovascular

• No history of active angina
• No history of significant ventricular arrhythmia
• No history of deep vein thrombosis
• No myocardial infarction within the past 6 months
• No acute abnormality by EKG
• No uncontrolled arrhythmia

Pulmonary

• No history of pulmonary embolism

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 1 highly-effective and 1 additional method of contraception for 28 days before, during, and for 4 weeks after study participation
• No known HIV disease
• Thyroid-stimulating hormone normal
• Serum anticonvulsant levels normal (for patients on anticonvulsants)
• No frequent vomiting and/or any other medical condition (e.g., partial bowel obstruction) that would preclude oral medication intake
• No preexisting neuropathy greater than grade 1
• No uncontrolled seizures
• No other concurrent medical condition that would preclude study participation

Expected Enrollment

A total of 21-50 patients will be accrued for this study within 1.5 years.

Outline

This is a multicenter study.

Patients receive oral temozolomide once daily on days 1-42 and oral thalidomide once daily on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses of therapy beyond CR.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 2 years.

Krown SE, Niedzwiecki D, Hwu WJ, et al.: Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain: high rate of thromboembolic events (CALGB 500102). Cancer 107 (8): 1883-90, 2006.[PUBMED Abstract]

Hwu WJ, Lis E, Menell JH, et al.: Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study. Cancer 103 (12): 2590-7, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Susan Krown, MD, Protocol chair		Ph: 212-639-7426; 800-525-2225 Email: krowns@mskcc.org

Registry Information
Official Title		A Phase II Study Of Temozolomide And Thalidomide In Patients With Metastatic Melanoma In The Brain
Trial Start Date		2003-10-15
Registered in ClinicalTrials.gov		NCT00072163
Date Submitted to PDQ		2003-09-17
Information Last Verified		2004-12-10
NCI Grant/Contract Number		CA31946

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