Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Conditions
Keywords
recurrent ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cavity cancer
Brief summary
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
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.
Interventions
DRUGtopotecan hydrochloride
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response | Every other cycle for the first 6 months, then every 3 months x2, then every 6 months until disease progression or study withdrawal | 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. |
| 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
| Measure | Time frame |
|---|---|
| Reason Off Study Therapy | study entry through end of study treatment, up to 5 years |
Countries
United States
Participant flow
Recruitment details
Regimen 1 (Topotecan 1.25 mg/m2) recruitment ended early due to lack of interest by institutions.
Participants by arm
| Arm | Count |
|---|---|
| Regimen I (Topotecan 1.25 mg/m2) Regimen I Topotecan 1.25 mg/m2 IV days 1-5 of a 21-day cycle until disease progression or adverse effects prohibit further therapy | 15 |
| Regimen II (Topotecan 4.0 mg/m2) Regimen II 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 | 65 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Wrong primary | 0 | 1 |
Baseline characteristics
| Characteristic | Regimen I (Topotecan 1.25 mg/m2) | Regimen II (Topotecan 4.0 mg/m2) | Total |
|---|---|---|---|
| Age, Customized 40-49 years | 2 Participants | 5 Participants | 7 Participants |
| Age, Customized 50-59 years | 3 Participants | 29 Participants | 32 Participants |
| Age, Customized 60-69 years | 4 Participants | 17 Participants | 21 Participants |
| Age, Customized 70-79 years | 5 Participants | 12 Participants | 17 Participants |
| Age, Customized > 79 years | 1 Participants | 2 Participants | 3 Participants |
| Cell Type Adenocarcinoma, Unspecified | 0 participants | 5 participants | 5 participants |
| Cell Type Clear Cell Carcinoma | 1 participants | 1 participants | 2 participants |
| Cell Type Endometrioid Adenocarcinoma | 0 participants | 2 participants | 2 participants |
| Cell Type Mixed Epithelial Carcinoma | 1 participants | 5 participants | 6 participants |
| Cell Type Other Carcinoma | 0 participants | 1 participants | 1 participants |
| Cell Type Serous Adenocarcinoma | 13 participants | 50 participants | 63 participants |
| Cell Type Undifferentiated Carcinoma | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 15 participants | 65 participants | 80 participants |
| Sex: Female, Male Female | 15 Participants | 65 Participants | 80 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 15 | 60 / 65 |
| serious Total, serious adverse events | 8 / 15 | 10 / 65 |
Outcome results
Primary
Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0
Time frame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Population: Eligible and treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Leukopenia | 10 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Neutropenia | 14 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Anemia | 5 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Nausea/vomiting | 1 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Other Gastrointestinal | 1 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Infection | 1 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Musculoskeletal | 0 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Pulmonary | 1 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Pain | 0 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Thrombocytopenia | 7 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Neurologic | 0 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Constitutional | 1 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Cardiovascular | 1 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Musculoskeletal | 1 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Thrombocytopenia | 6 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Neutropenia | 18 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Pulmonary | 2 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Anemia | 9 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Constitutional | 2 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Nausea/vomiting | 1 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Pain | 4 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Other Gastrointestinal | 0 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Cardiovascular | 0 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Leukopenia | 6 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Infection | 2 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Toxicity Criteria for Adverse Events Version 2.0 | Neurologic | 1 Participants |
Primary
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.
Time frame: Every other cycle for the first 6 months, then every 3 months x2, then every 6 months until disease progression or study withdrawal
Population: Eligible and evaluable participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regimen I (Topotecan 1.25 mg/m2) | Objective Tumor Response | Increase Disease | 2 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Objective Tumor Response | Indeterminate | 1 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Objective Tumor Response | Partial Response | 4 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Objective Tumor Response | Stable Disease | 8 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Objective Tumor Response | Stable Disease | 32 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Objective Tumor Response | Increase Disease | 21 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Objective Tumor Response | Partial Response | 8 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Objective Tumor Response | Indeterminate | 4 Participants |
Secondary
Reason Off Study Therapy
Time frame: study entry through end of study treatment, up to 5 years
Population: Eligible and evaluable participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Regimen I (Topotecan 1.25 mg/m2) | Reason Off Study Therapy | Disease Progression | 9 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Reason Off Study Therapy | Refused further treatment | 3 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Reason Off Study Therapy | Other | 0 Participants |
| Regimen I (Topotecan 1.25 mg/m2) | Reason Off Study Therapy | Toxicity as permitted | 3 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Reason Off Study Therapy | Other | 9 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Reason Off Study Therapy | Disease Progression | 47 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Reason Off Study Therapy | Refused further treatment | 7 Participants |
| Regimen II (Topotecan 4.0 mg/m2) | Reason Off Study Therapy | Toxicity as permitted | 2 Participants |