Radiation Therapy and Chemotherapy in Treating Patients With Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best way to give radiation therapy when given together with topotecan and cisplatin in treating patients with locally advanced cervical cancer. This trial is also studying the best dose of topotecan when given in this regimen. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as topotecan and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the safety and tolerability of pelvic radiotherapy, cisplatin, and topotecan in patients with locally advanced cervical cancer. II. Determine the maximum tolerated dose (MTD) of topotecan when administered in this regimen in this patient population. SECONDARY OBJECTIVES: I. Determine the site of recurrence (local vs distant) in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of topotecan. Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive cisplatin IV and topotecan IV over 30 minutes once weekly for a total of 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experiences dose-limiting toxicity. Once the MTD is determined, an additional cohort of 20 patients receives treatment as above at the MTD. After completion of study treatment, patients are followed periodically for 5 years.

Official Title
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A PHASE I STUDY OF PELVIC RADIATION THERAPY WITH CONCOMITANT WEEKLY CISPLATIN AND TOPOTECAN CHEMOTHERAPY IN PATIENTS WITH CERVICAL CARCINOMA WITHOUT EXTRA-PELVIC METASTASIS

Conditions
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Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Stage IB Cervical Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer, Stage IVA Cervical Cancer

Intervention / Treatment
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* Drug: Topotecan Hydrochloride Liposomes
* Radiation: 3-Dimensional Conformal Radiation Therapy
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary invasive carcinoma of the uterine cervix Stages IB2, II, IIIB, and IVA disease Any cell type No known metastasis to scalene nodes or organs outside the radiation field No known intraperitoneal metastases No evidence of extrapelvic disease based on negative CT or PET scan Must enroll within 8 weeks of diagnosis Performance status - GOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Creatinine normal Creatinine clearance > 50 mL/min Prior ureteral obstruction allowed provided stent or nephrostomy tube has been placed No renal abnormalities, such as pelvic kidney, horseshoe kidney, or prior renal transplantation that would require modification of radiation fields Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except nonmelanoma skin cancer No septicemia or severe infection No other medical or psychiatric condition that would preclude study compliance No prior chemotherapy for any prior malignancy No prior cytotoxic chemotherapy for this malignancy No prior radiotherapy for any prior malignancy No prior pelvic or abdominal radiotherapy for this malignancy No prior therapy for this malignancy
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: Treatment (topotecan hydrochloride, radiation, cisplatin)<br>Patients undergo radiotherapy 5 days a week for 6 weeks. Patients receive cisplatin IV and topotecan IV over 30 minutes once weekly for a total of 6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: Topotecan Hydrochloride Liposomes<br>* Given IV<br>* Other names: Brakiva;Radiation: 3-Dimensional Conformal Radiation Therapy<br> <br> * Other names: Radiation Conformal Therapy;Drug: Cisplatin<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of patients with acute toxicity assessed by Common Terminology Criteria for Adverse Events version 3.0 |  | Up to 30 days after completion of radiation therapy | 
| Incidence of patients with chronic toxicity assessed by Common Toxicity Criteria Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (CTC RTOG/EORTC) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Site of treatment failure | Identified as local versus distant. | Up to 5 years |