Chemotherapy and Pelvic Hypofractionated Radiation Followed by Brachytherapy for Cervical Cancer

Study Overview
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Brief Summary
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The main goal of this trial is to assess the safety and response rate to concomitant chemotherapy and external hypofractionated radiotherapy followed by brachytherapy in patients with clinical stage III cervical cancer. The trial will take place in the National Cancer Institute (INCan). Patients will be randomized into two groups: chemotherapy with external standard fractionated radiotherapy (45 Gy in 25 fractions) followed by brachytherapy or chemotherapy with external hypofractionated radiotherapy (37.5 Gy in 15 fractions) followed by brachytherapy.

Detailed Description
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The primary endpoint will be to assess the safety and efficacy to concomitant chemoradiotherapy followed by brachytherapy in cervical cancer clinical stage III. Secondary endpoints comprises security profile, survival rates, quality of life and related costs. The data obtained by this protocol will allow to determine the effect of hypofractionated radiation therapy and its possible adverse effects. Side effects will be classified according to version 4.03 of CTCAE guidelines. The highest CTCAE grade will be obtained for each type of event, for each patient and the Radiation Therapy Oncology Group (RTOG) scale will be applied to evaluate the events related to conventional and hypofractionated radiotherapy, as well as brachytherapy. Quality of life (QOL) will be evaluated using EORTC QLQ-CX24 and EORTC QLQ-C30, both have been validated and available in Mexican Spanish. Direct and indirect expenses related to the treatment will be evaluated based on the treatment costs stipulate by the institution and the information obtained by the social workers.

Official Title
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Phase II Randomized Controlled Trial of Concomitant Chemoradiotherapy With Standard Fractionation Compared to Hypofractionated Concomitant Chemoradiotherapy Followed by Brachytherapy, for Clinical Stage III Cervical Cancer Patients

Conditions
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Cervical Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women over 18 years old Cervical Cancer at IIIA, IIIB y IIIC1 FIGO´s clinical stages Histology: squamous, adenosquamous or adenocarcinoma No previous treatment No distance metastases, discard by Positron Emission Tomography (PET)/CT Functional State ECOG (Eastern Cooperative Oncology Group) 0-2 Complete Blood count obtained at least 14 days before admission to the study with adequate bone marrow function defined as: Absolute neutrophil count ≥ 1,500 cell/mm3 Platelets ≥ 100,000 cell/mm3 Hemoglobin ≥ 10.0 g/dl Leukocyte count ≥ 4000 cell/mm3 Adequate Renal Function defined as: Serum Creatinine ≤ 1.5 mg/dl within 14 days before admission to the study Patients with HIV infection (human immunodeficiency virus) must have a CD4 cell count ≥ 350 cells / mm3 measured within 14 days prior to study entry (no HIV test is required) The patient must understand the protocol and provide the specific informed consent of the study before admission Negative pregnancy test Exclusion Criteria: Patients who had chemotherapeutic, surgical and/or radiotherapy treatment for female reproductive tract pathologies Previous invasive neoplasia (except non-melanoma skin cancer) unless there is complete remission of the disease of 3 years minimum (For example, breast cancer or oral cavity cancer) Previous systemic chemotherapy for current cervical cancer, take into account that prior chemotherapy for a different cancer is accepted, as long as they have been at least 3 years Severe active or non-controlled co-morbidities, defined as: Unstable angina and/or congestive heart failure that required hospitalization in the last 6 months. Transmural myocardial infarction in the last 6 months. Acute bacterial or fungal infection requiring intravenous antibiotics at the beginning of the study. Chronic obstructive pulmonary disease exacerbation or another respiratory disease that requires hospitalization or that contraindicates the trial therapy at the time of admission. Crohn's disease or ulcerative colitis. Prior allergic reaction to cisplatin or other drugs based on platinum. Other factors that contraindicate experimental therapy.

Ages Eligible for Study
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Minimum Age: 18 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: Standard treatment<br>Cisplatin 40mg/m2 weekly and concomitant pelvic radiotherapy (45 Gray/25 fractions) followed by brachytherapy 28Gray at point A. | Radiation: Standard therapy<br>* All patients will be treated with external beam radiotherapy with 50 Gray in 25 fractions (1.8-2 Gray / fraction). They will be treated once a day, 5 days a week. If photon energy 6 MV or 10 MV is used, the patient should be treated with a 4-field technique using anterior/posterior fields and 2 lateral fields. The specification of the dose is in terms of a dose to a point at or near the center of the target volume. For all field dispositions, the dose specification point is the common isocenter of all beams.<br>|
| Experimental: Experimental treatment<br>Cisplatin 40mg/m2 weekly and hypofractionated concomitant external radiotherapy (37,50 Gray/15 fractions) followed by brachytherapy 28 Gray at point A. | Radiation: Hypofractionated therapy<br>* All patients will be treated with an external beam of 37.5 Gray in 15 fractions (2.5 Gray / fraction). They will be treated once a day, 5 days a week. If photon energy 6 MV or 10 MV is used, the patient should be treated with a 4-field technique using the anterior/posterior field and 2 lateral fields. The specification of the dose is in terms of a dose to a point at or near the center of the target volume. For all field dispositions, the dose specification point is the common isocenter of all beams.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and late toxicity | Number of Participants With Treatment-Related Adverse Events as Assessed by RTOG | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment efficacy | Hypofractionated radiotherapy is similar in toxicity and disease control compared to standard external beam treatment | 2 years | 
| Disease-free survival rate | Number of participants dead of disease at two years according to kaplan-meyer analysis | 2 years | 
| Overall survival rate | Number ofpParticipants dead at two years according to kaplan-meyer analysis | 2 years | 
| Satisfaction assessed by EORTC | Assessed individual's overall satisfaction with life and general sense of personal well-being by ERTC QLQ-C30 and QLQ-CX24 questionaire | 2 years | 
| Direct and indirect costs related to treatment. | Direct costs related to the treatment. Indirect costs related to the treatment (transport, housing, food, etc.) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypofractionated radiotherapy, Brachytherapy