Adaptive RadioTherapy for OroPharynx Cancer

Dysphagia Clinical Trial

— ART-OPC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04901234
• Other study ID #: ART-OPC
• Status: Recruiting
• Phase: Phase 2
• Start date: July 30, 2021
• Est. completion date: December 2026

Study information

• Verified date: December 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dysphagia
• MRI
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Radiotherapy Side Effect
• Radiotherapy; Complications

Intervention

Radiation:
• Standard radiotherapy +/- chemotherapy
No radiotherapy adaptation unless major dosimetric deviation
• Experimental radiotherapy +/- chemotherapy
Systemic MRI-based radiotherapy adaptation mid-treatment

Locations

Country	Name	City	State
Australia	Austin Health	Melbourne
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)	Austin Health

Countries where clinical trial is conducted

Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Locoregional control		at 6 months, 2 and 5 years
Other	Disease-free survival		at 6 months, 2 and 5 years
Other	Overall survival		at 6 months, 2 and 5 years
Other	Complete response rate		at 6 months
Other	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]
Primary	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	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]