Adaptive RadioTherapy for OroPharynx Cancer

NCT ID: NCT04901234

Last Updated: 2023-12-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-30
• Study Completion Date: 2026-12-31

Brief Summary

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.

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.

Conditions

Oropharynx Cancer; Radiotherapy; Complications; Radiotherapy Side Effect; Dysphagia; MRI

Keywords

Oropharynx cancer; Radiotherapy; Adaptation; Magnetic resonance imaging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Standard radiotherapy +/- chemotherapy

Intervention Type: RADIATION

No radiotherapy adaptation unless major dosimetric deviation

Adaptive radiotherapy

Systematic radiation treatment plan adaptation according to the shrinking tumour on mid-treatment MRI.

Group Type: EXPERIMENTAL

Experimental radiotherapy +/- chemotherapy

Intervention Type: RADIATION

Systemic MRI-based radiotherapy adaptation mid-treatment

Interventions

Standard radiotherapy +/- chemotherapy

No radiotherapy adaptation unless major dosimetric deviation

Intervention Type: RADIATION

Experimental radiotherapy +/- chemotherapy

Systemic MRI-based radiotherapy adaptation mid-treatment

Intervention Type: RADIATION

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Austin Health

OTHER_GOV

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Austin Health

Melbourne, , Australia

Site Status: NOT_YET_RECRUITING

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Australia; Canada

Facility Contacts

Sweet Ping Ng, MD PhD

Role: primary

Mom Phat

Role: primary

Silvine Benth

Role: backup

Other Identifiers

ART-OPC

Identifier Type: -

Identifier Source: org_study_id