Cervical Cancer Radiotherapy by Use of VMAT, Individualized Polyradiosensitization and Interstitial Brachytherapy

Study Overview
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Brief Summary
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The purpose of this study is to define an effectiveness of concurrent chemoradiotherapy of cervical cancer patients treated by VMAT (volumetric arc therapy) based external beam radiotherapy, polyradiosensitization by cisplatin and gemcitabine and interstitial brachytherapy.

Detailed Description
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Now cisplatin based concurrent chemoradiotherapy for cervical cancer is a standard treatment modality. But we consider that the treatment results could be improved by several ways: 1. use of VMAT (volumetric arc therapy) based external beam radiotherapy could decrease toxicity by reducing of unnecessarily irradiated tissue volumes; 2. in addition to cisplatin gemcitabine could enhance tumor cell damaging effect of radiation; 3. interstitial brachytherapy could provide higher radiation dose boost to high risk tumor volume while sparing surrounding organs at risk.

Official Title
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Improvement of Locally Advanced Cervical Cancer Radiotherapy Efficacy by Use of Volumetric Arc Therapy, Individualized Polyradiosensitization and Interstitial Brachytherapy

Conditions
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Cervical Cancer

Intervention / Treatment
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* Radiation: Volumetric Arc Radiotherapy
* Radiation: Interstitial brachytherapy
* Drug: Cisplatin
* Drug: Gemcitabine
* Genetic: PIK3CA
* Genetic: KRAS
* Genetic: BRAF
* Genetic: RRM1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary invasive carcinoma of the uterine cervix Previously untreated disease Any cell type Stage IB2, IIA, IIB, IIIA, IIIB, or IVA Para-aortic lymph nodes negative by radiologic evaluation or by biopsy if CT scan is suspicious for adenopathy No known metastases to scalene nodes or other organs outside the radiotherapy field Study enrollment within 8 weeks of diagnosis Performance status - GOG 0-2 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times normal SGOT no greater than 3 times normal Creatinine less than 2.0 mg/dL No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) that would require modification of radiotherapy fields No bilateral ureteral obstruction allowed unless treated with stent or nephrostomy tube Not pregnant Fertile patients must use effective contraception No septicemia or severe infection No circumstance that would preclude study completion or follow-up No other malignancy within the past 5 years except nonmelanoma skin cancer No prior cytotoxic chemotherapy No prior pelvic or abdominal radiotherapy No prior therapy for this malignancy Exclusion Criteria: Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events.(Note: Serum Pregnancy tests must be obtained in women of child bearing potential). Sexually active females may not participate unless they have agreed to use an effective contraceptive method (such as abstinence, diaphragm, condom, or intrauterine device) to prevent pregnancy for the duration of the study. Growth factor(s): Growth factors that support platelet or white cell number or function must not have been administered within the past 28 days. Erythropoietic drug(s): Erythropoietin or related hormones must not have been administered within the past 28 days. Infection: Patients who have an uncontrolled infection. Evidence of distant metastases Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years. Prior systemic chemotherapy within the last three years. Prior radiotherapy to the pelvis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: Classical treatment<br>Classical concurrent cisplatin based chemoradiotherapy of cervical cancer. PIK3CA, KRAS, BRAF and RRM1 mutations rates. | Radiation: Volumetric Arc Radiotherapy<br>* Volumetric Arc Radiotherapy<br>Drug: Cisplatin<br>* Weekly Cisplatin<br>* Other names: CDDP;Genetic: PIK3CA<br>* PIK3CA mutations rate<br>Genetic: KRAS<br>* KRAS mutations rate<br>Genetic: BRAF<br>* BRAF mutations rate<br>Genetic: RRM1<br>* RRM1 mutations rate<br>|
| Experimental: GemInterBraVMAT<br>Concurrent chemoradiotherapy of cervical cancer patients treated by VMAT (volumetric arc radiotherapy) based external beam radiotherapy, polyradiosensitization by cisplatin and gemcitabine and interstitial brachytherapy. PIK3CA, KRAS, BRAF and RRM1 mutations rates. | Radiation: Volumetric Arc Radiotherapy<br>* Volumetric Arc Radiotherapy<br>Radiation: Interstitial brachytherapy<br>* Interstitial High Dose Rate Brachytherapy<br>Drug: Cisplatin<br>* Weekly Cisplatin<br>* Other names: CDDP;Drug: Gemcitabine<br>* Weekly Gemcitabine<br>* Other names: Gemcitabine Hydrochloride;Genetic: PIK3CA<br>* PIK3CA mutations rate<br>Genetic: KRAS<br>* KRAS mutations rate<br>Genetic: BRAF<br>* BRAF mutations rate<br>Genetic: RRM1<br>* RRM1 mutations rate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse Rate (local and/or distant) and Number of Deaths Due to Any Cause |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progressive Disease |  | 4 years | 
| Incidence of acute toxicity |  | Up to 30 days after completion of radiation therapy | 
| Incidence of late toxicity |  | Up to 2 years after completion of radiation therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, interstitial brachytherapy, gemcitabine, volumetric arc therapy