RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining oxaliplatin with topotecan in
treating patients who have previously treated ovarian epithelial, primary peritoneal, or
fallopian tube cancer.
- Determine the maximum tolerated dose and dose-limiting toxic effects of oxaliplatin and
topotecan in patients with previously treated ovarian epithelial cancer, primary
peritoneal cancer, or fallopian tube cancer.
- Determine the qualitative and quantitative toxic effects of this regimen in these
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the antitumor activity of this treatment regimen in these patients.
- Determine the correlation between the pharmacokinetic and safety data of this regimen
in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and topotecan IV continuously
on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity. Patients with measurable disease who achieve a
response may receive additional therapy at the discretion of the principal investigator.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and topotecan until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6
patients experience dose-limiting toxicity.
Patients are followed through day 30.
PROJECTED ACCRUAL: A minimum of 15 patients will be accrued for this study.
- Histologically or cytologically confirmed ovarian epithelial cancer, primary
peritoneal cancer, or fallopian tube cancer
- Prior chemotherapy required
- Measurable or evaluable disease
- No symptomatic, untreated brain metastases
- 18 and over
- Karnofsky 70-100%
- At least 4 months
- WBC greater than 3,000/mm^3
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
- Bilirubin no greater than 1.5 times upper limit of normal (ULN) OR
- SGOT no greater than 2.5 times ULN (5 times ULN if liver metastases)
- Creatinine no greater than 1.5 times ULN OR
- Creatinine clearance at least 50 mL/min
- No uncontrolled symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
- No other active cancer
- No prior allergy to platinum compounds
- No prior allergic reactions to appropriate antiemetics (e.g., serotonin or
antagonists) administered concurrently with study
- No other uncontrolled concurrent illness (e.g., infection)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
PRIOR CONCURRENT THERAPY:
- See Chemotherapy
- No concurrent colony stimulating factors during topotecan administration
- See Disease Characteristics
- No prior high-dose chemotherapy requiring bone marrow or peripheral blood stem cell
- At least 4 weeks since prior chemotherapy and recovered
- Not specified
- No prior radiotherapy to whole pelvic field
- At least 2 weeks since prior radiotherapy and recovered
- No unresolved sequelae resulting from prior surgery
- At least 4 weeks since other prior investigational drug
- No other concurrent investigational agents
- No other concurrent anticancer therapy