R115777 in Treating Patients With Recurrent or Metastatic Non-small Cell Lung Cancer

A Phase II Study of Farnesyl Transferase Inhibitor R115777 in Patients With Advanced Non-Small Cell Lung Cancer

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 R115777 in treating patients who have recurrent or metastatic non-small cell lung cancer.

OBJECTIVES:

• Assess the response rate of patients with recurrent or metastatic non-small cell lung cancer when treated with tipifarnib.
• Determine the clinical toxicities of this treatment in these patients.
• Assess the overall survival and time to progression of this patient population when treated with this regimen.
• Evaluate the inhibition of protein farnesylation in vivo and correlate such inhibition to plasma levels of tipifarnib.
• Evaluate the occurrence of CYP450 polymorphisms and relate these to drug toxicity, pharmacokinetics, and response to this treatment in this patient population.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed recurrent or metastatic non-small cell lung cancer (NSCLC)

• Measurable disease

  • At least 20 mm in at least one dimension

  • Nonmeasurable is defined as any of the following:

    • 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

• No CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

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

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 3 times ULN (no greater than 5 times ULN in case of hepatic metastases)

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No other prior malignancy in past 5 years except adequately treated basal cell or squamous cell skin cancer or other adequately treated noninvasive carcinomas
• No other concurrent severe underlying disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic, gene, or immunotherapy

Chemotherapy

• No prior chemotherapy for NSCLC except low dose cisplatin as radiosensitizer

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy to less than 25% of bone marrow allowed

Surgery

• Not specified