Perifosine in Treating Patients With Metastatic or Recurrent Malignant Melanoma

A Phase II Study Of Perifosine (D-21266) In Previously Untreated Patients With Metastatic Or Recurrent Malignant Melanoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of perifosine in treating patients who have metastatic or recurrent malignant melanoma.

OBJECTIVES:

• Determine the efficacy of perifosine, in terms of response rate, in previously untreated patients with metastatic or recurrent malignant melanoma.
• Assess the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral perifosine daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or partial response (PR) receive 2 additional courses after documentation of CR or stable PR (i.e., no further tumor shrinkage).

Patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant melanoma

• Metastatic or recurrent disease deemed incurable by standard therapies

• Clinically and/or radiologically documented disease by at least 1 site that is unidimensionally measurable as follows:

  • At least 20 mm by x-ray or physical exam
  • At least 10 mm by spiral CT scan
  • At least 20 mm by non-spiral CT scan
  • Bone lesions are not considered measurable
  • Outside previously irradiated area unless evidence of progression or new lesions within irradiated field

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 2.5 times ULN

Renal

• Creatinine no greater than ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions to compounds of similar chemical or biological composition to perifosine
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
• No ongoing or active infection
• No other concurrent uncontrolled medical illness, psychiatric illness, or social situation that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 months since prior adjuvant immunotherapy
• No prior immunotherapy for recurrent/metastatic disease

Chemotherapy

• No prior chemotherapy (including regional therapy)
• No other concurrent cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy (except for low-dose, nonmyelosuppressive radiotherapy)

Surgery

• At least 4 weeks since prior major surgery

Other

• No other concurrent anticancer therapy or investigational agents