Nitrocamptothecin in Treating Patients With Advanced Ovarian Cancer

Open Label Phase II Study on RFS 2000 (9-Nitro-camptothecin, 9-NC) Administered as a "5 Days On-2 Days Off" Oral Treatment in Advanced Ovarian 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 nitrocamptothecin in treating patients who have advanced ovarian cancer.

OBJECTIVES:

• Determine the objective response rate and duration of response in patients with advanced ovarian cancer treated with nitrocamptothecin.
• Determine the probability of objective response as expressed by the response rate in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease status (sensitive vs refractory).

Patients receive oral nitrocamptothecin daily for 5 consecutive days each week for 3 weeks. Treatment continues every 3 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease (SD) receive up to 4 additional courses past SD. Patients who achieve partial response (PR) or complete response (CR) receive a minimum of 2 additional courses past PR or CR.

Patients are followed every 6 weeks until disease progression or the initiation of another antitumor therapy.

PROJECTED ACCRUAL: A total of 28-50 patients (14-25 per stratum) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven metastatic or unresectable locally advanced progressive ovarian cancer that has failed first line platinum and taxane based regimen

  • Refractory disease defined by a relapse within 1 year after completion of first line therapy
  • Sensitive disease defined by a relapse greater than 1 year after completion of first line therapy

• Minimum of 1 target lesion that can be accurately measured in at least 1 dimension

  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan

• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase, SGOT, and SGPT no greater than 2.5 times ULN (no greater than 5 times ULN if hepatic metastases present)

Renal:

• Creatinine no greater than 1.7 mg/dL

Cardiovascular:

• No ischemic heart disease within the past 6 months
• Normal 12 lead electrocardiogram

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No unstable systemic disease or active uncontrolled infections
• No other prior or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer or cone biopsied carcinoma of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF) with nitrocamptothecin

Chemotherapy:

• See Disease Characteristics
• Greater than 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Greater than 4 weeks since prior radiotherapy

Surgery:

• Greater than 2 weeks since prior major surgery

Other:

• No other concurrent anticancer agents
• No other concurrent investigational therapy