VNP40101M in Treating Patients With Relapsed or Refractory Locally Advanced or Metastatic Small Cell Lung Cancer

A Phase II Trial of Cloretazine™ (VNP40101M) for Patients With Relapsed or Refractory Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well VNP40101M works in treating patients with recurrent or refractory locally advanced or metastatic small cell lung cancer.

OBJECTIVES:

• Determine the overall response rate (partial and complete) in patients with relapsed or refractory locally advanced or metastatic small cell lung cancer treated with VNP40101M.
• Determine the toxic effects of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease state (sensitive relapse [progressive disease > 3 months after responding to first-line chemotherapy] vs resistant disease [progressive disease during or ≤ 3 months after first-line chemotherapy]).

Patients receive VNP40101M IV over 15-30 minutes once weekly for 3 weeks. Treatment repeats every 6 weeks for up to 6 courses. Patients achieving a complete response (CR) receive 2 additional courses of therapy after CR.

After completion of study treatment, patients are followed periodically for up to 18 months.

PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Cytologically confirmed small cell lung cancer

  • Locally advanced or metastatic disease
  • Recurrent or progressive disease after first-line standard cytotoxic therapy

• Measurable or evaluable disease

• Brain metastasis allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 2 months
• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 2.5 mg/dL
• AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active uncontrolled bleeding
• No active infection
• Must not require supplemental oxygen at rest
• No active heart disease
• No myocardial infarction within the past 3 months
• No uncontrolled congestive heart failure
• No uncontrolled arrhythmias
• No uncontrolled coronary artery disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 3 weeks since prior radiotherapy, biologic therapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)

  • Prior radiotherapy within the past 3 weeks allowed if exposure involves no more than 30% of bones with significant bone marrow-producing capabilities (e.g., vertebral bodies and long bones)

• At least 2 weeks since prior surgery or hormonal therapy

• Must not require any immediate palliative treatment including surgery

• Must have recovered from prior anticancer therapy

  • Persistent, stable chronic toxic effects ≤ grade 1 are allowed

• No more than 1 prior systemic chemotherapy regimen for locally advanced or metastatic disease

• No other concurrent anticancer therapy

• No other concurrent investigational agent

• No concurrent disulfiram