Clinical trial NCT04901234: Adaptive RadioTherapy for OroPharynx Cancer
Official title: Adaptive RadioTherapy for Locally Advanced OroPharynx Cancer (ART-OPC) A Phase II Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oropharynx Cancer
Radiotherapy; Complications
Radiotherapy Side Effect
Dysphagia
MRI
Keywords: Oropharynx cancer
Radiotherapy
Adaptation
Magnetic resonance imaging
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Austin Health
First posted: 2021-05-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase II open label randomized controlled trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Patient-reported dysphagia
timeFrame: at 6 months post treatment
Secondary outcomes:
measure: Acute and late toxicities
timeFrame: From treatment start to 5-years after the end of chemoradiation]
Other outcomes:
measure: Locoregional control
timeFrame: at 6 months, 2 and 5 years
measure: Disease-free survival
timeFrame: at 6 months, 2 and 5 years
measure: Overall survival
timeFrame: at 6 months, 2 and 5 years
measure: Complete response rate
timeFrame: at 6 months
measure: Patient-reported dysphagia
timeFrame: [Time Frame: At baseline, and 1-, 3-, 12- months post-treatment, and yearly up to 5 years after the end of chemoradiation]
Locations:
city: Melbourne
country: Australia
facility: Austin Health
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
References: