Topotecan in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving topotecan in different dosing schedules may kill more tumor cells. PURPOSE: This phase II trial is studying how well topotecan works in treating patients with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity of topotecan, in terms of frequency and duration of tumor response, in patients with recurrent platinum-sensitive ovarian epithelial, fallopian tube, or primary peritoneal cancer. Determine the nature and degree of toxicity of this regimen in these patients. Secondary Determine the duration of progression-free survival and overall survival in patients treated with these regimens. Determine the effects of prognostic variables (i.e., initial performance status, age, and mucinous or clear cell histology) in patients treated with these regimens. OUTLINE: This is a multicenter study. Patients receive topotecan IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: Approximately 38-110 patients (19-55 per treatment arm) will be accrued for this study within 15-30 months.

Official Title
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A Randomized Phase II Evaluation of Topotecan (NSC #609699) Administered Daily x 5 Every 3 Weeks vs Weekly Topotecan in the Treatment of Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cancer Recurrent disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan At least 1 target lesion not in a previously irradiated field Received 1, and only 1, prior platinum-based chemotherapy regimen for primary disease containing carboplatin, cisplatin, or other organoplatinum compound Initial treatment may have included high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment Patients who have not received prior paclitaxel may receive a second regimen that includes paclitaxel Platinum-sensitive disease Treatment-free interval* without clinical evidence of progressive disease for > 6 months after prior response to a platinum-based regimen NOTE: *Non-platinum maintenance or consolidation therapy is not included in calculation of the treatment-free interval Not eligible for a higher priority GOG protocol (i.e., any active phase III GOG protocol for the same patient population) PATIENT CHARACTERISTICS: Age 18 and over Performance status GOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Creatinine clearance > 40 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No sensory or motor neuropathy > grade 1 No active infection requiring antibiotics No other invasive malignancy within the past 5 years except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 weeks since prior biologic or immunologic agents for the malignancy No more than 1 prior non-cytotoxic (biologic or cytostatic) regimen (e.g., monoclonal antibodies, cytokines, or small molecule inhibitors of signal transduction) for recurrent disease No concurrent cytokines during the first course of study treatment No concurrent pegfilgrastim Chemotherapy See Disease Characteristics See Biologic therapy Recovered from prior chemotherapy No other prior cytotoxic chemotherapy for recurrent disease, including retreatment with initial chemotherapy regimen No prior topotecan Endocrine therapy At least 1 week since prior hormonal therapy for the malignancy Concurrent hormone replacement therapy allowed Radiotherapy See Disease Characteristics Recovered from prior radiotherapy No prior radiotherapy to > 25% of marrow-bearing areas Surgery Recovered from prior surgery Other At least 3 weeks since other prior therapy for the malignancy No prior anticancer therapy that would preclude study treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topotecan 1.25 mg/m2 IV days 1-5 of a 21 day cycle<br>Topotecan 1.25 mg/m2 IV days 1-5 of a 21 day cycle until disease progression or adverse effects prohibit further therapy | Drug: topotecan hydrochloride<br> <br> |
| Active Comparator: Topotecan 4.0 mg/m2 IV day 1, 8 and 15 of a 28 day cycle<br>Topotecan 4.0 mg/m2 IV day 1, 8 and 15 of a 28 day cycle until disease progression or adverse effects prohibit further therapy | Drug: topotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response | Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0): Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease. | Every other cycle for the first 6 months, then every 3 months x2, then every 6 months until disease progression or study withdrawal | 
| Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 |  | Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reason Off Study Therapy |  | study entry through end of study treatment, up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cavity cancer