CRP on Radiobiological and Clinical Studies on Viral-Induced Cancer's Response to Radiotherapy

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to study clinical effects of two/four high dose rate (HDR) brachytherapy applications and teletherapy with or without weekly cisplatin in cervix cancer.

Detailed Description
-----------------
This study uses 2x2 design to test external beam radiotherapy (46 Gy in 23 daily fractions) with and without HDR brachytherapy (2 fractions of 9 Gy versus 4 fractions of 7 Gy) with and without weekly Cisplatin (40 mg/sqm) The overall objective was to test the clinical outcome and toxicity of a resource-sparing schedule of radiotherapy with or without chemotherapy treatment for cervix cancer, to detect molecular markers that will predict tumor control/resistance and to establish whether E6 and E7 viral proteins predict cellular radiosensitivity in oxic and hypoxic conditions in vitro and tumor control/resistance in vivo. A new component of the CRP was added, for which the objective is to optimize the data capture, provide more details of normal tissue outcomes following cancer treatments in developing countries and validate this approach using patients participating in the ongoing CRP. This will be achieved by exploring data capture using the questionnaire template on a computer in face-to-face interviews (active data collection) and comparing it with standard data collection obtained from the clinical notes (passive data collection) during the still ongoing CRP E3.30.24. The method of data collection will be chosen at random for each case stratified by centre. The reason for using an ongoing CRP is that it will test the usefulness of the new method and validate it in a multicentre study. During the performance of the new CRP, the same institutions as for E3.30.24 will be engaged.

Official Title
-----------------
CRP on Radiobiological and Clinical Studies on Viral-induced Cancer's Response to Radiotherapy With Comprehensive Morbidity Assessment

Conditions
-----------------
Cervix Cancer

Intervention / Treatment
-----------------
* Radiation: Radiotherapy
* Radiation: Radiotherapy
* Radiation: Radiotherapy/Cisplatin
* Radiation: Radiotherapy/Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Histologically confirmed cervix cancer. FIGO stage IIB and IIIB Age over 18 years Karnofsky status >/= 50 No significant medical contraindications to the administration of full dose chemotherapy. Adequate bone marrow function -- Haemoglobin ³ 10 g/dl without or with transfusion, white blood count ³ 4000/mL, platelet count ³ 140,000/mL. Adequate renal function: creatinine < 1.2 mg/dL or 120 μmol/l (urinary diversion is permitted). Electrolytes and calcium within normal limits for institution. Liver function tests if clinically indicated. Tests have to be obtained within 30 days before registration. Expected good compliance for follow-up. Written informed consent for participation in this study. EXCLUSION CRITERIA: Recent malignancy, other than the index cervical carcinoma or non-melanoma cutaneous cancers, diagnosed within 5 years of entry Life expectancy <6 months, for any reason other than the index cervical carcinoma Any severe medical ailment, continuing pregnancy, or breast feeding, as conditions that interfere in present treatment Previous chemotherapy in past 1 year Severe psychiatric disorder, making compliance and follow-up difficult. Paraaortic nodes (PAN >1 cm), suspicious or positive for metastatic involvement on radiological imaging. (Note: patients with positive pelvic lymph nodes are still eligible for the study, but they cannot have suspicious or positive PAN.) Bilateral hydronephrosis Prior radiation to the pelvis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBR plus 2 HDBT fractions<br>External Beam Radiotherapy High Dose Brachytherapy (2 fractions of 9Gy) | Radiation: Radiotherapy<br>* External Beam Radiation 46Gy in 23 daily fractions High Dose Brachytherapy 2 fractions of 9Gy<br>|
| Active Comparator: EBR plus 4 fractions HDBT<br>External Beam Radiotherapy High Dose Brachytherapy (4 fractions of 7Gy) | Radiation: Radiotherapy<br>* External Beam Radiotherapy 46Gy in 23 daily fractions High Dose Brachytherapy 4 fractions of 7Gy<br>|
| Experimental: EBR/2 HDBT fractions/Chemotherapy<br>External Beam Radiation High Dose Brachytherapy (2 fractions of 9Gy) Cisplatin | Radiation: Radiotherapy/Cisplatin<br>* External Beam Radiation 46Gy in 23 daily fractions High Dose Brachytherapy 2 fractions of 9Gy Cisplatin 40 mg/sqm weekly<br>|
| Experimental: EBR/4 fractions HDBT/chemotherapy<br>External Beam Radiation High Dose Brachytherapy (4 fractions of 7Gy) Cisplatin | Radiation: Radiotherapy/Cisplatin<br>* External Beam Radiotherapy 46Gy in 23 daily fractions High Dose Brachytherapy 4 fractions of 7Gy Cisplatin 40mg/sqm weekly<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcome |  | 5 years | 
| Treatment Toxicity |  | 3 months | 
| Molecular markers that will predict tumor control/resistance |  | 5 years | 
| Whether E6 and E7 viral proteins predict cellular radiosensitivity in oxic and hypoxic conditions in vitro and tumor control/resistance in vivo |  | 5 years | 
| Effectiveness of a questionnaire template on a computer in face-to-face interviews in a multicentre multinational study. |  | 2 years |