Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy drugs before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy is more effective followed by surgery or combined with radiation therapy in treating cervical cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by radical hysterectomy with that of chemotherapy plus radiation therapy in treating patients who have stage IB or stage II cervical cancer.

Detailed Description
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OBJECTIVES: Compare the overall and progression-free survival of patients with stage IB2, IIA, or IIB cervical cancer treated with neoadjuvant cisplatin-based chemotherapy followed by radical hysterectomy vs standard therapy comprising concurrent radiotherapy and cisplatin-based chemotherapy. Compare the toxicity of these regimens in these patients. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, FIGO stage, age (18 to 50 vs 51 to 75), and histological subtype (adenomatous vs non-adenomatous component). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive neoadjuvant cisplatin-based chemotherapy on day 1. Treatment repeats every 21 days. Within 6 weeks after the last chemotherapy course, patients undergo a type III-V Piver-Rutledge radical hysterectomy. Patients with positive lymph nodes or tumor invasion into the parametria or less than 5 mm from the resection borders after surgery receive standard adjuvant external beam radiotherapy once daily, 5 days a week, for 5-5.6 weeks (25-28 treatment days) followed by external boost radiotherapy or brachytherapy for 1 or 2 days. Arm II: Patients receive standard therapy comprising radiotherapy as in arm I concurrently with cisplatin-based chemotherapy once weekly for 6 weeks. Adjuvant hysterectomy is allowed, but not recommended, in case of histologically proven residual tumor. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. For patients in both arms, cisplatin may be combined with other chemotherapeutics as long as the minimum platinum dose is given. Quality of life is assessed at baseline and at 6, 12, 18, and 24 months. Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 686 patients (343 per treatment arm) will be accrued for this study within 3.8 years.

Official Title
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Randomized Phase III Study Of Neoadjuvant Chemotherapy Followed By Surgery Vs. Concomitant Radiotherapy And Chemotherapy In FIGO Ib2, IIa>4 cm or IIb Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Procedure: conventional surgery
* Procedure: neoadjuvant chemotherapy
* Radiation: brachytherapy
* Radiation: radiation therapy
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cervical cancer, including the following subtypes: Squamous cell carcinoma Adenosquamous cell carcinoma Adenocarcinoma (excluding small cell, clear cell, and other rare variants of the classical adenocarcinoma) FIGO stage IB2, IIA (greater than 4 cm), or IIB PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin less than 1.46 mg/dL Renal: Creatinine clearance greater than 60 mL/min Other: No other prior or concurrent malignancy except adequately treated basal cell skin cancer No psychological, familial, sociological, or geographical condition that would preclude study Not pregnant PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: Not specified Other: No other concurrent anticancer agent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Chemotherapy followed by surgery<br>neoadjuvant chemotherapy (Cisplatin) followed by surgery (radial hysterectomy) | Procedure: conventional surgery<br>* Radial hysterectomy<br>Procedure: neoadjuvant chemotherapy<br>* Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.<br>Drug: cisplatin<br>* Minimal cumulative 225 mg/m2 (experimental arm). Cumulative 200-240 mg/m2 (comparator arm).<br>|
| Active Comparator: Radio-chemotherapy<br>Concomitant radiotherapy (external radiotherapy combined with external boost or brachytherapy) and chemotherapy (cisplatin) | Procedure: neoadjuvant chemotherapy<br>* Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.<br>Radiation: brachytherapy<br>* Brachytherapy at the end of external radiation. Minimal total dose (external with or without external boost + brachytherapy) of 75 Gy EQD2 to point A. Overall treatment less than 50 days.<br>Radiation: radiation therapy<br>* Between 45-50 Gy, in fractions of 1.8 to 2 Gy.<br>Drug: cisplatin<br>* Minimal cumulative 225 mg/m2 (experimental arm). Cumulative 200-240 mg/m2 (comparator arm).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival at 5 years |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IB cervical cancer, stage IIB cervical cancer, stage IIA cervical cancer, cervical squamous cell carcinoma, cervical adenocarcinoma, cervical adenosquamous cell carcinoma