Adaptive RadioTherapy for OroPharynx Cancer (ART-OPC)

Adaptive RadioTherapy for Locally Advanced OroPharynx Cancer (ART-OPC) A Phase II Randomized Trial

This is a phase II randomized trial, where patients with histologically proven squamous cell carcinoma of oropharynx that have primary tumor (T3 - T4) in place, treated with curative intent chemoradiation, will be randomized to systematic mid-treatment MRI-based radiotherapy adaptation vs. standard of care. The primary objective is to compare patient-rated dysphagia (as assessed by the MD Anderson Dysphagia Inventory composite score at 6 months post-treatment in patients undergoing routine mid-treatment MR-guided radiotherapy adaptation vs. in patients receiving the current standard of care.

Study Overview

• Status: Recruiting
• Conditions: MRI; Dysphagia; Oropharynx Cancer; Radiotherapy Side Effect; Radiotherapy; Complications
• Intervention / Treatment: Radiation: Standard radiotherapy +/- chemotherapy; Radiation: Experimental radiotherapy +/- chemotherapy

Detailed Description

Background: Dysphagia was shown to be the main driver of adverse quality of life after head and neck radiotherapy. Over the 7-week radiotherapy course, patients with head and neck cancers undergo significant anatomical changes, including weight loss and tumor shrinkage (with complete response at mid-treatment in as high as 50% of patients). The current standard of care is to maintain the same radiotherapy plan for the entire treatment duration, unless major dosimetric deviations are detected. The use of MRI for treatment adaptation has the advantage of increased soft tissue contrast and is being integrated into several clinical practises with the recent development of MR-Linac technology. However, there is currently no demonstrated clinical advantage from the use of MRI for treatment adaptation in head and neck cancer.

Primary objective: To compare patient-rated dysphagia (as assessed by the MD Anderson Dysphagia Inventory composite score at 6 months post-treatment in patients undergoing routine mid-treatment MR-guided radiotherapy adaptation vs. in patients receiving the current standard of care.

Methods: This is a phase II randomized trial, where patients with histologically proven squamous cell carcinoma of oropharynx that have primary tumor (T3 - T4) in place, treated with curative intent chemoradiation, will be randomized to systematic mid-treatment MRI-based radiotherapy adaptation vs. standard of care. Patients with contra-indications to MRI will be excluded. The study will use a 2-sided, independent-sample t-test with an alpha level of 0.05 and power of 80%, with a 1:1 randomization between the 2 arms. In order to detect a 10-point improvement in the MD Anderson Dysphagia Index (MDADI) and assuming that the quality of life scores would be normally distributed with a standard deviation of 18, a total of 104 patients will be required (52 in each arm), which has been increased to 120 patients overall (60 patients in each arm) to account for a 10% dropout rate in completion of the quality of life scoring at 6 months post-treatment. An independent DSMB will review the pooled standard deviation of the interim data collected for this trial after 40 patients overall have been recruited (20 in each arm) the value of the standard deviation used to calculate the sample size required. The DSMB will inform the study team if there is potential to reduce the sample size if the standard deviation was much lower than 18 (i.e. <=15 would result in a reduction of 25% in patients required), which will potential reduce the length of the trial. Patients will be stratified by institution and recruited in blocks of 4 to ensure a balance between arms at the interim assessment.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • Not yet recruiting
    • Austin Health
    • Contact: Sweet Ping Ng, MD PhD
    • Principal Investigator: Sweet Ping Ng, MD PhD
• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Recruiting
      • Centre Hospitalier de L'Universite de Montreal
      • Contact: Mom Phat; Phone Number: 514-890-8254; Email: mom.phat.chum@ssss.gouv.qc.ca
      • Contact: Silvine Benth; Phone Number: 514-890-8254; Email: mom.phat.chum@ssss.gouv.qc.ca
      • Principal Investigator: Edith Filion, MD
      • Sub-Investigator: Houda Bahig, MD PhD

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.
• Stage T3-T4N0-3 as per AJCC 8th edition
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Biopsy proven diagnosis of squamous cell carcinoma of the oropharynx.
• Planned for curative radiotherapy +/- chemotherapy
• For females of child-bearing age, a negative pregnancy test
• Patients treated with induction chemotherapy can be included if they have residual tumor in place.

Exclusion Criteria:

• Previous irradiation of the head and neck (HNC) region, excluding superficial radiation therapy for non-melanomatous skin cancer
• 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.
• Patients with contra-indications to MRI will be excluded.

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
Active Comparator: Standard radiotherapy; Radiotherapy as planned at baseline, with replanning allowed only if significant weight loss or change in anatomy due to unforeseen circumstances (eg that would affect dosimetry and treatment delivery of baseline treatment plan). No adaptation to shrinking tumour is allowed.	Radiation: Standard radiotherapy +/- chemotherapy; No radiotherapy adaptation unless major dosimetric deviation
Experimental: Adaptive radiotherapy; Systematic radiation treatment plan adaptation according to the shrinking tumour on mid-treatment MRI.	Radiation: Experimental radiotherapy +/- chemotherapy; Systemic MRI-based radiotherapy adaptation mid-treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported 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 6 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute and late toxicities	Rate of grade ≥ 3 late toxicity as per CTCAE v5.0	From treatment start to 5-years after the end of chemoradiation]

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional control		at 6 months, 2 and 5 years
Disease-free survival		at 6 months, 2 and 5 years
Overall survival		at 6 months, 2 and 5 years
Complete response rate		at 6 months
Patient-reported 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.	[Time Frame: At baseline, and 1-, 3-, 12- months post-treatment, and yearly up to 5 years after the end of chemoradiation]

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Austin Health

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Radiotherapy; Adaptation; Oropharynx cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms
• Other Study ID Numbers: ART-OPC

Drug and device information, study documents

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