De-Escalation Radiotherapy in Patients With Low-Risk HPV-Related Oropharyngeal Squamous Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out whether radiotherapy to some of the lymph node areas can be safely omitted to decrease side effects without increasing the risk of the tumour coming back.

Detailed Description
-----------------
The standard or usual treatment for this disease includes radiotherapy or radiotherapy combined with chemotherapy or antibody therapy. These treatments are highly effective at curing most patients with HPV-related cancer of the oropharynx, but short and long-term side effects from treatment can be significant.

Official Title
-----------------
A Phase II Single Arm Trial of Elective Volume Adjusted De-Escalation Radiotherapy (EVADER) in Patients With Low-Risk HPV-Related Oropharyngeal Squamous Cell Carcinoma

Conditions
-----------------
Oropharyngeal Cancer

Intervention / Treatment
-----------------
* Radiation: Radiation
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with pathologically proven diagnosis of HPV-related OPSCC Clinical stage T1-3 N0-1 M0 (UICC/AJCC 8th Ed.) Patients must be eligible for definitive RT or CRT Must be ≥ 18 years of age Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires in either English or French Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. In accordance with CCTG policy, protocol treatment is to begin within 3 weeks of patient registration Women/men of childbearing potential must have agreed to use a highly effective contraceptive method The following radiological investigations must be done within 8 weeks of randomization: CT or MR of head and neck (MRI is recommended for base-of-tongue primary tumors); PET-CT scan. Patient must consent to provision of, and investigator(s) must confirm location and commit to obtain a representation of formalin-fixed paraffin block of non-cytology tumour tissue in order that the specific correlative marker assays described in Section 12 (Correlative Studies) may be conducted. Please see the Correlative Manual for details Patient must consent to provision of samples of blood and plasma (for circulating cell free DNA) in order that the specific correlative marker assays described may be conducted. Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Exclusion Criteria: Previous chemotherapy or radiotherapy treatment for head and neck cancer Patients with an unknown primary.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Two Treatment Options<br>Option #1 - Radiotherapy 35 fractions, 5/wk, 7 wks 70Gy/56Gy Cisplatin 100mg/m2 on day 1, 22 and 43 or 40mg mg/m2/wk for 7 wks Option #2 - Radiation only-35 fraction, 6/wk, 6wks 70Gy/56Gy | Radiation: Radiation<br>* 35 fractions, 5/wk, 7 wks 70Gy/56Gy, or 35 fractions, 6/wk, 6 wks, 70Gy/56Gy, or 35 fractions, 5/wk, 7 wks OR 6/wk, 6 wks 70Gy/56Gy<br>* Other names: No available;Drug: Cisplatin<br>* 100 mg/m2 on day 1, 22, and 43 or 40 mg/m2 /wk for 7 wks<br>* Other names: No available;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival | Time to first progress event or censoring in year | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time to death or censoring in year | 5 years | 
| Local control | Percentage of patients with local control | 5 years | 
| Regional Control | Percentage of patients with regional control | 5 years | 
| Locoregional control | Percentage of patients with local and regional control | 5 years | 
| Distant Metastasis-Free Survival | Time to distant metastasis or censoring in year | 5 years |