Clinical Response and Toxicity of Hypo-fractionated Chemoradiotherapy in Cervix Cancer

Study Overview
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Brief Summary
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Uterine cervix cancer can be treated definitively with concurrent chemoradiation (external beam radiotherapy and chemotherapy) followed by high dose rate brachytherapy. Treatment duration can be shortened by increasing the dose per fraction of treatment which can reduce costs and patient exposure. The aim of our study is to determine the non-inferiority of hypofractionated radiotherapy compared with conventional treatment.

Detailed Description
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In this study we aim to determine if clinical response and toxicity of radiotherapy hypofractionation is non-inferior to the conventional treatment. We will enroll 60 eligible patients with cervical cancer stage IB to IIIC and randomly allocate them into the intervention (hypofractionation) group or the control (standard) groups. The patients in the intervention group will receive external beam radiotherapy(EBRT) to a total dose of 40 Gy in 15 fractions within 3 weeks concurrently with weekly chemotherapy with cisplatin 40mg/m2 (total of 3 cycles). Whereas, the control group will receive EBRT to a total dose of 45 Gy in 25 fractions within 5 weeks concurrently with weekly chemotherapy with cisplatin 40mg/m2 (total of 5 cycles). All patients from both groups will undergo high dose rate brachytherapy one week after completion of EBRT to a total dose of 28 Gy per 4 weekly sessions. Patients will be evaluated regarding early and late toxicities as described by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at the completion of brachytherapy, and at 3 months, 6 months, and 3 years from completion of treatment. Also, clinical response will be evaluated through dynamic contrast enhanced pelvic MRI 3 months, 1 year, and 3 years after completion of brachytherapy.

Official Title
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Comparison of Clinical Response and Toxicity of Hypo-fractionated Chemoradiation With Standard Treatment in Patients With Uterine Cervix Cancer

Conditions
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Cervix Uteri Cancer

Intervention / Treatment
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* Radiation: Hypofractionated EBRT
* Radiation: Standard EBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathology of squamous cell carcinoma (SCC), adenocarcinoma, adenosquamous carcinoma of uterine cervix- International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA, IIB, IIIA, IIIB (due to hydronephrosis without creatinine clearance compromise), IIIC1 (if less than 3 lymph nodes with size less than 3cm, and without involvement of common iliac chain)- Patient eligible for definitive chemoradiotherapy followed by brachytherapy Exclusion Criteria: Creatinine clearance less than 30ml/min, any histology other than the above, requirement of paraaortic lymph node irradiation, inflammatory bowel disease, connective tissue disorders, previous pelvic radiotherapy, FIGO stage IA or IV, Eastern Cooperative Oncology Group (ECOG) performance status greater than 2, History of previous hysterectomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Hypofractionated<br>EBRT 40Gy/15fr | Radiation: Hypofractionated EBRT<br>* EBRT dose of 40Gy in 15 fractions over 3 weeks plus 3 weekly infusions of cisplatin 40mg/m2<br>|
| Active Comparator: Control Group<br>EBRT 45Gy/ 25fr | Radiation: Standard EBRT<br>* EBRT dose of 45Gy in 25 fractions over 5 weeks plus 5 weekly infusions of cisplatin 40mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early toxicity | Early treatment-related toxicity within 3 months after completion of treatment as defined by CTCAE 5.0. | 3 months after completion of treatment | 
| Early response | Early response to treatment at 3 months after treatment completion based on dynamic contrast-enhanced pelvic MRI findings | 3 months after completion of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late toxicity | Late treatment-related toxicity within 1 and 3 years after completion of treatment as defined by CTCAE 5.0. | 1 and 3 years after completion of treatment | 
| Progression-free survival | Time from randomization to progression(based on MRI and physical examination), death, or last follow up; whichever that occurs first | 5 years | 
| Disease-specific survival | Time from randomization to death from cervical cancer or last follow-up; whichever that occurs first. | 5 years | 
| Overall survival | Time from randomization to death from any reason or last follow-up; whichever that occurs first. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionation, Brachytherapy, Chemoradiation