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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cervix Uteri Cancer
• Intervention / Treatment: Radiation: Hypofractionated EBRT; Radiation: Standard EBRT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kasra Kolahdouzan, M.D.; Phone Number: +989144083785; Email: k-kolahdouzan@razi.tums.ac.ir
• Study Contact Backup: Name: Ebrahim Esmati, M.D.; Phone Number: +989126880306; Email: eb_esmati@yahoo.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1419733141
    • Recruiting
    • Imam Khomeini Hospital Complex
    • Contact: Kasra Kolahdouzan, M.D.; Phone Number: +989144083785; Email: k-kolahdouzan@razi.tums.ac.ir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated; EBRT 40Gy/15fr	Radiation: Hypofractionated EBRT; EBRT dose of 40Gy in 15 fractions over 3 weeks plus 3 weekly infusions of cisplatin 40mg/m2
Active Comparator: Control Group; EBRT 45Gy/ 25fr	Radiation: Standard EBRT; EBRT dose of 45Gy in 25 fractions over 5 weeks plus 5 weekly infusions of cisplatin 40mg/m2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Afsaneh Maddah-Safaei, M.D., Tehran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2028

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Chemoradiation; Brachytherapy; Hypofractionation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Uterine Neoplasms
• Other Study ID Numbers: 9711880002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No