Temozolomide and Thalidomide in Treating Patients With Stage III or Stage IV Melanoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00005815

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of melanoma by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness temozolomide plus thalidomide in treating patients who have stage III or stage IV melanoma that cannot be removed during surgery.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Melanoma Melanoma (Skin)	Drug: temozolomide Drug: thalidomide	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose (MTD) of temozolomide using an extended continuous schedule in combination with thalidomide in patients with advanced melanoma.
Determine the response rate to this combination using an extended continuous schedule at the MTD in 30 patients who have advanced metastatic melanoma without brain metastases and in 15 patients who have metastatic melanoma in the brain.
Further characterize the safety and toxicity of this combination in these patients.

OUTLINE: This is a dose escalation study of temozolomide (phase I) followed by a response rate determination study (phase II).

Patients receive oral temozolomide daily for 6 weeks followed by 2-4 weeks of rest. Patients receive oral thalidomide daily for the entire 8-10 week course. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Once the MTD is determined, additional patients are accrued to receive treatment with temozolomide and thalidomide at the recommended phase II dose.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for phase I and then an additional 45 patients (15 with CNS disease, 30 without CNS disease) will be accrued for phase II of this study within 18 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of Temozolamide and Thalidomide in the Treatment of Advanced Melanoma

Study Start Date :

Dec 1, 1999

Actual Primary Completion Date :

Aug 1, 2004

Actual Study Completion Date :

Aug 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic malignant melanoma that is considered unresectable
Stage III or IV ocular, mucosal, or cutaneous melanoma
Measurable disease
No CNS disease (phase I only)

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 70-100%

Life expectancy:

Not specified

Hematopoietic:

Absolute granulocyte count at least 1,500/mm^3
Platelet count at least 150,000/mm^3

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGOT/SGPT no greater than 3 times ULN
Alkaline phosphatase no greater than 3 times ULN

Renal:

Creatinine no greater than 1.5 times ULN

Cardiovascular:

No history of active angina
No myocardial infarction within past 6 months
No history of significant ventricular arrhythmia requiring medication with antiarrhythmics

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 4 weeks before and after study
No frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction)
No preexisting neurotoxicity grade 2 or greater
No serious concurrent infections treated with antibiotics
No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study
No psychiatric disorders that would preclude study compliance
No other medical condition or reason that would preclude study
No other malignancy within the past 2 years except:
Nonmelanoma skin cancer
Carcinoma in situ of the cervix
History of T1a or b prostate cancer detected incidentally at TURP and comprising less than 5% of resected tissue with PSA normal since TURP
No AIDS related illness
HIV negative

PRIOR CONCURRENT THERAPY:

Recovered from prior therapy

Biologic therapy:

At least 4 weeks since prior biologic therapy
At least 4 weeks since prior immunotherapy
No concurrent immunotherapy

Chemotherapy:

No prior systemic chemotherapy for metastatic melanoma
No other concurrent chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

At least 4 weeks since prior radiotherapy, interstitial brachytherapy, or radiosurgery
At least 3 weeks since prior radiotherapy to the brain if brain metastases from melanoma
Prior radiotherapy to only indicator lesion allowed provided recent evidence of disease progression at that site
No concurrent radiotherapy