Stereotactic Boost and Short-course Radiation Therapy for Oropharynx Cancer (SHORT-OPC)

Stereotactic Boost and SHOrt-course Radiation Therapy for HPV-associated OroPharynx Cancer Trial: A Randomized Multicentric Phase III Trial

This is a randomized clinical trial comparing the outcomes of short-course chemoradiation consisting in stereotactic boost to the gross tumor and de-esclalated chemoradiation to the elective neck in human papilloma associated oropharynx cancer vs. the current standard 7-week course chemoradiation.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Oropharynx Cancer; Human Papilloma Virus
• Intervention / Treatment: Radiation: SABR boost and de-escalated chemoradiation; Radiation: Standard chemoradiation

Detailed Description

Concurrent platinum-based chemoradiation remains the standard of care in locally advanced head and neck cancer. The current standard radiation regimen consists in a 7-week course of conventionally fractionated radiotherapy to the gross tumor volume (GTV), along with bilateral prophylactic neck irradiation to an elective dose of ~ 50 Gy in 2 Gy per fraction. In addition to being cumbersome, the current protracted daily radiation course is associated with high rates of acute and late toxicities and significant deterioration of patients' quality of life. In the light of the remarkably improved prognosis of the distinct subgroup of HPV-OPC, there is growing interest for treatment de-intensification strategies in contemporaneous OPC cohorts.

Stereotactic ablative radiotherapy (SABR) allows for ultra-precise delivery of ablative radiation dose over a small number of fractions, by combining sharp dose gradients with use of optimal image guidance. The increased conformity and reduced margins used in SABR can substantially reduce the dose to surrounding organs at risk and could therefore reduce toxicity. In addition, previous work has shown that an elective dose of 40 Gy in 2 Gy per fraction, in conjunction with chemotherapy, is sufficient for microscopic sterilisation of cancer cells and can translate into a reduction of toxicities.

The goal of this trial is to compare the efficacy and safety of short-course chemoradiation consisting in stereotactic boost to the gross tumor of 14 Gy in 2 fractions followed by de-esclalated chemoradiation (40 Gy in 20 fractions and concurrent 2 cycles of Cisplatin 100mg/m2) in human papilloma associated oropharynx cancer vs. the current standard 7-week course chemoradiation (70 Gy in 33 fractions with 2-3 cycles of Cisplatin 100mg/m2).

This is an open label randomized phase III non inferiority trial. Patients will be randomized using a 1:1 ratio between the standard and the experimental arm and will be stratified by tumor stage and use of concurrent chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Diane Trudel; Phone Number: 514-890-8254; Email: diane.dt.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada
      • Recruiting
      • London Health Sciences Center
      • Contact: Karen Eddy; Phone Number: (519) 685-8500; Email: Karen.Eddy@lhsc.on.ca
  • Quebec
    • Montreal, Quebec, Canada, H2X 1R6
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal
      • Contact: Mom Phat; Phone Number: 26906 514-890-8000; Email: mom.phat.chum@ssss.gouv.qc.ca
      • Principal Investigator: Houda Bahig
      • Sub-Investigator: Phuc-Félix Nguyen-Tan

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
• Ability to provide written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Biopsy proven diagnosis of squamous cell carcinoma of the oropharynx.
• Positive for HPV by p16 immunohistochemistry (IHC) or HPV in-situ hybridization (ISH)
• Clinical stage T1-3, N1 M0 (Stage I-II) as per AJCC 8th edition.
• Primary tumor < 30 cc
• Planned for curative chemoradiation
• For females of child-bearing age, a negative pregnancy test

Exclusion Criteria:

• Clinical N3 classification, as per AJCC 8th edition
• Clinically overt extranodal extension (ENE). As per AJCC 8th edition, clinically overt ENE is defined as invasion of the skin, infiltration of musculature/fixation to adjacent structures on clinical examination, cranial nerve, brachial plexus, sympathetic trunk or phrenic nerve invasion with dysfunction).
• Previous irradiation of the head and neck region
• Previous surgery of the HNC region (except for incisional or excisional biopsies)
• Pregnancy or breastfeeding
• Connective tissue disease
• Any medical condition that could, in the opinion of the investigator, prevent follow-up after radiotherapy.
• Non-Cisplatin concurrent chemotherapy
• Prior induction chemotherapy

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: SABR boost and de-escalated chemoradiation; SABR boost of 14 Gy in 2 fractions to the GTV, immediately followed by de-escalated chemoradiation. De-escalated chemoradiation will consist in 40 Gy in 20 fractions with concurrent high dose Cisplatin (3-weekly, 100 mg/m2) for 2 cycles, aiming for a cumulative dose of 200 mg/m2.	Radiation: SABR boost and de-escalated chemoradiation; Stereotactic body radiotherapy boost to the gross tumor volume to a dose of 14 Gy in 2 fractions, followed by cisplatin-based chemoradiation to a dose of 40 Gy in 20 fractions
Active Comparator: Standard chemoradiation; The standard arm will consist of conventionally radiation to a dose of 70 Gy in 33 fractions concurrently with high dose Cisplatin (3-weekly, 100 mg/m2) for 2-3 cycles, aiming for a cumulative dose of ≥ 200 mg/m2.	Radiation: Standard chemoradiation; Standard Cisplatin-based chemoradiation to a dose of 70 Gy in 33 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Patient alive with no local, regional or distant recurrence at 2 years after the end of chemoradiation	2 years after the end of chemoradiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subacute toxicity	Rate of grade ≥ 3 subacute toxicity	Between 2 and 6 months after the end of chemoradiation
Acute toxicity	Rate of grade ≥ 3 acute toxicity	Less than 2 months after the end of chemoradiation
Late toxicity	Rate of grade ≥ 3 late toxicity	Between 6 months and 5-years after the end of chemoradiation
OS	Overall survival	At 2- and 5-years after the end of chemoradiation
Head and neck symptom burden	Patient-reported head and neck symptom burden as measured by the MD Anderson Symptom Inventory Head and Neck Cancer Module. The core and head and neck cancer specific symptoms are rated on a 0-10 scale to indicate the presence and severity of the symptoms. Lower scores represent better functioning and quality of life.	At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation
Dysphagia	Patient-reported dysphagia as measured by the MD Anderson Dysphagia Index. Overall score ranges from 0 to 100, with higher score representing better functioning and quality of life.	At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation
Time from treatment start to return to work	Time from first day of treatment start to first day of return to work.	Measured in days and reported at 2-years post-treatment
locoregional control	Patient alive with locoregional control	At 2- and 5-years after the end of chemoradiation

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: M.D. Anderson Cancer Center; Jewish General Hospital; London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
• Investigators: Study Chair: Phuc-Felix Nguyen-Tan, MD, Centre Hospitalier de l'Universite de Montreal (CHUM); Principal Investigator: Jack Phan, MD PhD, M.D. Anderson Cancer Center; Principal Investigator: Khalil Sultanem, MD, Montreal Jewish General Hospital; Study Chair: Houda Bahig, MD PhD, Centre Hospitalier de l'Universite de Montreal (CHUM); Principal Investigator: David Palma, MD PhD, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: November 17, 2019
• First Submitted That Met QC Criteria: November 23, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Radiotherapy; Chemotherapy; Human papilloma virus; Stereotactic body radiotherapy; head and neck cander; Oropharynx cancer; De-intensification
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Papilloma; Oropharyngeal Neoplasms
• Other Study ID Numbers: SHORT-OPC

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
• product manufactured in and exported from the U.S.: No