Topotecan in Treating Women With Persistent or Recurrent Cervical 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 tumor cells from dividing so they stop growing or die. PURPOSE: This phase II trial is studying how well topotecan works in treating women with persistent or recurrent cervical cancer.

Detailed Description
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OBJECTIVES: Determine the antitumor activity of topotecan in patients with persistent or recurrent carcinoma of the cervix that failed higher priority treatment protocols. Determine the nature and degree of toxicity of this drug in these patients. 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. Patient are followed for every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 1-2 years.

Official Title
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A Phase II Evaluation of Weekly Topotecan Hydrochloride (Hycamtin®, NSC #609699) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix

Conditions
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Cervical 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 carcinoma of the cervix Squamous cell or nonsquamous cell Persistent or recurrent disease Documented disease progression Measurable disease At least 1 unidimensionally measurable target lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Tumors within a previously irradiated field are considered non-target lesions unless disease progression is documented or a biopsy is obtained to confirm persistent disease at least 90 days after completion of prior radiotherapy Must have received 1 prior systemic chemotherapy regimen for persistent or recurrent squamous cell or nonsquamous cell carcinoma of the cervix Chemotherapy administered with primary radiotherapy as a radiosensitizer is not considered a systemic chemotherapy regimen 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 Other Sensory or motor neuropathy ≤ grade 1 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No other malignancy within the past 5 years except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy One prior non-cytotoxic (biologic or cytostatic) regimen for recurrent or persistent disease allowed, including, but not limited to, the following: Monoclonal antibodies Cytokines Small-molecule inhibitors of signal transduction At least 3 weeks since prior biologic or immunologic agents for cervical cancer No concurrent prophylactic growth factors, including filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim No concurrent prophylactic thrombopoietic agents Chemotherapy See Disease Characteristics Recovered from prior chemotherapy No more than 1 prior cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy) No prior topotecan Endocrine therapy At least 1 week since prior hormonal therapy for cervical cancer Concurrent hormone replacement therapy allowed Radiotherapy See Disease Characteristics Recovered from prior radiotherapy Surgery Recovered from prior surgery Other At least 3 weeks since other prior therapy for cervical cancer No prior cancer therapy that would preclude study participation

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topotecan<br>Topotecan weekly | Drug: topotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as 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. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; every 6 months thereafter until disease progression for up to 5 years. | 
| Number of Participants With Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | All participants assessed by CTCAE v3 (Common Terminology Criteria for Adverse Events version 3.0) including grade 0 (the number of participants not affected by the Adverse Event). | Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent cervical cancer, cervical squamous cell carcinoma