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

Gynecologic Oncology Group (GOG)

Status and phase: Completed; Phase 2

Conditions: Primary Peritoneal Cavity Cancer; Fallopian Tube Cancer; Ovarian Cancer

Treatments: Drug: topotecan hydrochloride

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00114166

CDR0000434848

GOG-0146Q

Details and patient eligibility

About

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.

Full 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.

Enrollment: 81 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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81 participants in 2 patient groups

Topotecan 1.25 mg/m2 IV days 1-5 of a 21 day cycle

Active Comparator group

Description:

Topotecan 1.25 mg/m2 IV days 1-5 of a 21 day cycle until disease progression or adverse effects prohibit further therapy

Treatment:

Drug: topotecan hydrochloride

Topotecan 4.0 mg/m2 IV day 1, 8 and 15 of a 28 day cycle

Active Comparator group

Description:

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

Treatment:

Drug: topotecan hydrochloride