CCI-779 in Treating Patients With Metastatic Melanoma

A Phase II Study Of CCI-779 (NSC 683864) In Metastatic 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 CCI-779 in treating patients who have metastatic melanoma.

OBJECTIVES:

• Determine the anti-tumor activity of CCI-779, in terms of progression-free survival, in patients with metastatic melanoma.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive CCI-779 IV over 30 minutes on day 1. Courses repeat every 7 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: Approximately 40-50 patients will be accrued for this study within 12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic melanoma that is incurable by surgery, radiotherapy, or limb perfusion

• Measurable disease

  • At least 20 mm by conventional techniques OR

  • At least 10 mm by spiral CT scan

  • The following are not considered measurable:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions

• Progressive disease

• No prior or concurrent CNS metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 4 months

Hematopoietic:

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

Hepatic:

• Bilirubin normal
• AST and ALT no greater than 2.5 times upper limit of normal
• Cholesterol no greater than 350 mg/dL (lipid-lowering therapy allowed)
• Triglycerides no greater than 300 mg/dL except for hydroxymethyl-glutaryl-coenzyme A reductase inhibitors

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

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
• HIV negative
• No prior allergic reactions to compounds of similar chemical or biological composition to study drug
• No ongoing or active infection
• No seizure disorder
• No autoimmune disease
• No psychiatric illness or social situation that would preclude study
• No other concurrent uncontrolled illness that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No more than 1 prior adjuvant biological therapy regimen
• No more than 1 prior biological therapy regimen for advanced disease
• At least 6 months since prior biological therapy or biochemotherapy and recovered
• Prior isolated limb perfusion with biological agent allowed if not to sole site of disease

Chemotherapy:

• See Biologic therapy

• Prior isolated limb perfusion with chemotherapy allowed if not to sole site of disease

• No more than 1 prior chemotherapy-containing regimen for advanced disease, regardless of adjuvant therapy

  • May be in addition to 1 prior biologic regimen for advanced disease OR
  • May have had 1 prior biochemotherapy regimen for advanced disease

• At least 3 weeks since prior chemotherapy and recovered

Endocrine therapy:

• At least 1 week since prior dexamethasone
• No concurrent glucocorticosteroid therapy

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Other:

• At least 1 week since prior phenobarbital, phenytoin, carbamazepine, or rifampin
• At least 3 weeks since other prior agents to treat malignancy
• At least 3 weeks since prior investigational agents
• No other concurrent investigational agents
• No concurrent drugs that are metabolized by or alter the level of cytochrome P450-3A