Head and Neck Cancer, Human Papilloma Virus, Oropharynx Cancer
Conditions
Keywords
head and neck cander, Oropharynx cancer, Human papilloma virus, Radiotherapy, Stereotactic body radiotherapy, Chemotherapy, De-intensification
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.
Interventions
RADIATIONSABR boost and de-escalated chemoradiation
Stereotactic body radiotherapy boost to the gross tumor volume to a dose of 14 Gy in 2 fractions, followed by cisplatin-based chemoradiation to a dose of 40 Gy in 20 fractions
RADIATIONStandard chemoradiation
Standard Cisplatin-based chemoradiation to a dose of 70 Gy in 33 fractions
Sponsors
Centre hospitalier de l'Université de Montréal (CHUM)
M.D. Anderson Cancer Center
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Jewish General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 2 years after the end of chemoradiation | Patient alive with no local, regional or distant recurrence at 2 years after the end of chemoradiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subacute toxicity | Between 2 and 6 months after the end of chemoradiation | Rate of grade ≥ 3 subacute toxicity |
| Acute toxicity | Less than 2 months after the end of chemoradiation | Rate of grade ≥ 3 acute toxicity |
| Late toxicity | Between 6 months and 5-years after the end of chemoradiation | Rate of grade ≥ 3 late toxicity |
| OS | At 2- and 5-years after the end of chemoradiation | Overall survival |
| locoregional control | At 2- and 5-years after the end of chemoradiation | Patient alive with locoregional control |
| Head and neck symptom burden | At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation | Patient-reported head and neck symptom burden as measured by the MD Anderson Symptom Inventory Head and Neck Cancer Module. The core and head and neck cancer specific symptoms are rated on a 0-10 scale to indicate the presence and severity of the symptoms. Lower scores represent better functioning and quality of life. |
| Time from treatment start to return to work | Measured in days and reported at 2-years post-treatment | Time from first day of treatment start to first day of return to work. |
| Dysphagia | At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation | 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. |
Countries
Canada
Contacts
CONTACTDiane Trudel
STUDY_CHAIRHouda Bahig, MD PhD
Centre hospitalier de l'Université de Montréal (CHUM)
STUDY_CHAIRPhuc-Felix Nguyen-Tan, MD
Centre hospitalier de l'Université de Montréal (CHUM)
PRINCIPAL_INVESTIGATORDavid Palma, MD PhD
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
PRINCIPAL_INVESTIGATORJack Phan, MD PhD
M.D. Anderson Cancer Center
PRINCIPAL_INVESTIGATORKhalil Sultanem, MD
Montreal Jewish General Hospital
Outcome results
None listed