Clinical trial NCT04178174: Stereotactic Boost and Short-course Radiation Therapy for Oropharynx Cancer
Official title: Stereotactic Boost and SHOrt-course Radiation Therapy for HPV-associated OroPharynx Cancer Trial: A Randomized Multicentric Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Head and Neck Cancer
Oropharynx Cancer
Human Papilloma Virus
Keywords: head and neck cander
Oropharynx cancer
Human papilloma virus
Radiotherapy
Stereotactic body radiotherapy
Chemotherapy
De-intensification
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: M.D. Anderson Cancer Center
name: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Jewish General Hospital
First posted: 2019-11-26
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 2 years after the end of chemoradiation
Secondary outcomes:
measure: Subacute toxicity
timeFrame: Between 2 and 6 months after the end of chemoradiation
measure: Acute toxicity
timeFrame: Less than 2 months after the end of chemoradiation
measure: Late toxicity
timeFrame: Between 6 months and 5-years after the end of chemoradiation
measure: OS
timeFrame: At 2- and 5-years after the end of chemoradiation
measure: locoregional control
timeFrame: At 2- and 5-years after the end of chemoradiation
measure: Head and neck symptom burden
timeFrame: At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation
measure: Dysphagia
timeFrame: At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation
measure: Time from treatment start to return to work
timeFrame: Measured in days and reported at 2-years post-treatment
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Houda Bahig, MD PhD
role: STUDY_CHAIR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Phuc-Felix Nguyen-Tan, MD
role: STUDY_CHAIR
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: David Palma, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Jack Phan, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montreal Jewish General Hospital
name: Khalil Sultanem, MD
role: PRINCIPAL_INVESTIGATOR
References: