Hypofractionated External-beam RadiOtherapy for Intact Cervical Cancer (HEROICC-Trial): A Feasibility Study

External radiation given in 25 fractions or so together with weekly chemotherapy and followed by 3 or 4 fractions of brachytherapy is the standard of care for patients with locally advanced cervical cancer.

This study investigates the role of shortened external radiotherapy regimen (hypofractionated radiotherapy) by randomizing patients to this experimental regimen versus the standard of care.The purpose of this study is to access the feasibility of patient accrual to this trial in the Canadian setting and to provide an initial evaluation of cancer response and treatment tolerability.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Experimental; Drug: Concurrent Chemotherapy; Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Standard of Care

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lucas C Mendez, MD; Phone Number: 519-685-8650; Email: Lucas.Mendez@lhsc.on.ca
• Study Contact Backup: Name: David D'Souza, MD; Phone Number: 519-685-8650; Email: David.DSouza@lhsc.on.ca

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Recruiting
      • BC Cancer - Kelowna
      • Contact: Hamid Raziee, MD; Email: hamid.raziee@bccancer.bc.ca
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Centre - London Regional Cancer Program
      • Contact: Lucas C Mendez, MD; Phone Number: 519-685-8650; Email: Lucas.Mendez@lhsc.on.ca
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Odette Cancer Centre - Sunnybrook Health Sciences Centre
      • Contact: Eric Leung, MD; Phone Number: (416) 480-5000; Email: eric.leung@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• International Federation of Gynecology and Obstetrics (FIGO) IA or IB1 cervical cancers if not surgical candidates, but amenable to definitive chemoradiotherapy as proposed in this trial.
• FIGO Stage IB2, IB3, IIA or IIB cervical cancers

• FIGO stage IIIC1 cervical cancers are candidates but must meet all the following criteria:

  1. largest node is less than 3 cm
  2. less than 3 pathological nodes
  3. No nodes located in the common iliac chain.
  4. Cervical confined or with parametrial invasion
• Histologically-confirmed invasive uterine cervical carcinoma of subtypes squamous cell, adenocarcinoma or adenosquamous cell
• Candidate for definitive chemoradiotherapy to be delivered with weekly cisplatin
• Brachytherapy candidate

Exclusion Criteria:

• FIGO stage IIIA, IIIB, IIIC2, IVA or IVB
• FIGO stage IIIC1 with node greater than 3 cm, common iliac node or greater than 2 pathological nodes
• Previous pelvic or abdominal radiotherapy
• Patients requiring paraaortic nodal irradiation
• Inflammatory bowel disease
• Connective tissue disorder (eg. scleroderma, systemic lupus erythematous)
• Neuroendocrine, glassy cell, small cell, adenoid cystic carcinoma, adenoid basal carcinoma, clear cell, serous, endometrioid, verrucous carcinoma, melanoma, and sarcoma histologies
• Patient unable to undergo MR scan
• Eastern Cooperative Oncology Group (ECOG) performance status greater than 3
• Not a cisplatin candidate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 EBRT+High-dose (HDR) Brachytherapy Experimental	Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Experimental; 40 Gy / 15 Fractions EBRT + HDR-Brachytherapy; Drug: Concurrent Chemotherapy; Weekly cisplatin 40 mg/m2 for a maximum of 5 cycles
Active Comparator: Arm 2 EBRT+High-dose (HDR) Brachytherapy Standard of Care	Drug: Concurrent Chemotherapy; Weekly cisplatin 40 mg/m2 for a maximum of 5 cycles; Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Standard of Care; 45 Gy / 25 Fractions EBRT + HDR-Brachytherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the feasibility in the Canadian Health Care System	This trial aims to investigate its feasibility in the Canadian health care system. Feasibility will be defined as the ability to consent and randomize 48 patients over 3 years from date of site activation.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumour response based on imaging	Tumour response rate on Magnetic resonance imaging (MRI) images will be graded as proposed in the EMBRACE 2 protocol	3.5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QoL) - Bowel and urinary quality of life as measured by the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.	QoL will be measured by the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. EPIC was initially created for assessment of QoL in patients with prostate cancers. This questionnaire was used in the NRG RTOG 1203 protocol (NCT01672892) and comprehensively assesses bowel function and bother (bowel summary domain) and urinary function, bother, incontinence and irritation/obstruction (urinary domain). The EPIC questionnaire contains 32 questions measuring patient function. Each question has a response option ranging from 0 or 1 (best) to 3, 4, or 5 (worst). The responses then correlate to a scoring scale of 0 to 100, where 0 is the best and 100 is the worst. The values vary from 0 to 100 for each question. The scores can then be added to come up with an overall quality of life score.	8 years
Quality of Life (QoL) is measured by European Organization for Research and Treatment of Cancer (EORTC) and Core 30 (QLQ-C30) QoL questionnaires	Two European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires (Core 30 (QLQ-C30). QLQ-C30 is used for all cancers and has several symptom scales, five functional scales (physical, emotional, social, role, cognitive) and a global health status scale. The QLQ-C30 responses are regarding function and symptoms are on a scale of 1 (not at all) to 4 (very much). Also included are questions about overall health and quality of life. Responses are on a scale of 1 (very poor) to 7 (excellent).	8 years
Quality of Life (QoL) - acute vaginal and sexual symptoms as measured by the cervical cancer module (QLQ-CX24)	QoL will be measured by the cervical cancer module (QLQ-CX24). QLQ-CX24 includes cancer - and treatment - related items and symptoms regarding sexuality. Acute and late vaginal and sexual QoL will be assessed using the QLQ-CX24 vaginal and sexual domains respectively. The QLQ-CX24 responses are regarding function and symptoms of sexual and vagina health. It is based on a scale of 1 (not at all) to 4 (very much).	8 years
Quality of Life (QoL) - late vaginal and sexual symptoms as measured by the cervical cancer module (QLQ-CX24)	QoL will be measured by the cervical cancer module (QLQ-CX24). QLQ-CX24 includes cancer - and treatment - related items and symptoms regarding sexuality. Acute and late vaginal and sexual QoL will be assessed using the QLQ-CX24 vaginal and sexual domains respectively. The QLQ-CX24 responses are regarding function and symptoms of sexual and vagina health. It is based on a scale of 1 (not at all) to 4 (very much).	8 years
Acute and late toxicity	This outcome is assessed by physicians during each follow-up appointment, and scored according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (18). Clinically relevant toxicities of gastrointestinal, genitourinary, vaginal and non-specific general symptoms (i.e. fatigue, malaise and pain) will be collected. Hematological disorders will also be collected through weekly blood work checks. Acute toxicities will be collected at baseline, and then weekly during radiotherapy/chemoradiotherapy and at 3 months after completion of radiation. Late toxicities will be collected from 3 months after completion of radiation onwards until the end of follow-up.	3 years and 3 months
Assessment of cancer down staging throughout EBRT.	To be assessed through volumetric comparison of gross tumor volume (GTV) and high risk clinical target volume (HR-CTV) contours in the pre-EBRT and brachytherapy MRI scans.	3 years
Progression-free survival	Defined as time from date of randomization to date of progression, date of death from any cause, or date of last follow-up, whichever occurs first. Cancer progression can be identified during physical exam, biopsy, or imaging of any kind.	8 years
Locoregional progression-free survival	Defined as time from date of randomization to date of locoregional progression, date of death from any cause, or date of last follow-up, whichever occurs first.	8 years
Metastasis-free survival	Defined as time from date of randomization to date of development of metastasis, date of death from any cause, or date of last follow-up, whichever occurs first.	8 years
Cervical cancer-specific survival	Defined as time from date of randomization to date of death attributed to cervical cancer, or date of last-follow-up, whichever occurs first.	8 years
Overall survival	Defined as time from date of randomization to date of death from any cause, or date of last follow-up, whichever occurs first.	8 years

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Academic Medical Organization of Southwestern Ontario
• Investigators: Principal Investigator: Lucas C Mendez, MD, London Health Sciences Centre, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Anticipated): December 14, 2023
• Study Completion (Anticipated): December 14, 2028

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hypofractionated External-beam Radiotherapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: HEROICC; ReDA ID#10482 (Other Identifier: Lawson Health Research Institute)

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