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

Phase 2

Active, not recruiting

Conditions: Oropharyngeal Cancer

Interventions: Radiation: Radiation
Drug: Cisplatin

Registration Number: NCT03822897

Lead Sponsor: Canadian Cancer Trials Group

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 103

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental arm	Radiation	This is a non-randomized, single-arm study evaluating elective volume-adjusted de-escalation radiotherapy. Patients receive one of two treatment options, based on treating physician discretion. Both options are considered part of a unified treatment strategy and analyzed as a single arm. * Option 1 (Chemoradiotherapy): Radiotherapy: 70 Gy to the high-risk volume and 56 Gy to the elective volume, delivered in 35 fractions over 7 weeks (5 fractions/week) Cisplatin: Either 100 mg/m² on days 1, 22, and 43 or 40 mg/m² weekly for 7 weeks * Option 2 (Radiotherapy Alone): Radiotherapy: 70 Gy to the high-risk volume and 56 Gy to the elective volume, delivered in 35 fractions over 6 weeks (6 fractions/week)
Experimental arm	Cisplatin	This is a non-randomized, single-arm study evaluating elective volume-adjusted de-escalation radiotherapy. Patients receive one of two treatment options, based on treating physician discretion. Both options are considered part of a unified treatment strategy and analyzed as a single arm. * Option 1 (Chemoradiotherapy): Radiotherapy: 70 Gy to the high-risk volume and 56 Gy to the elective volume, delivered in 35 fractions over 7 weeks (5 fractions/week) Cisplatin: Either 100 mg/m² on days 1, 22, and 43 or 40 mg/m² weekly for 7 weeks * Option 2 (Radiotherapy Alone): Radiotherapy: 70 Gy to the high-risk volume and 56 Gy to the elective volume, delivered in 35 fractions over 6 weeks (6 fractions/week)

Primary Outcome Measures

Name	Time	Method
Event-free Survival	2 years	Event free survival (EFS) is defined as the time from the date of registration to the date of first record of any of the following events: * Progression. * Surgery. * Non-protocol RT, chemotherapy, or biologic therapy (for the current cancer diagnosis) without documentation of the site of failure. * Death due to any cause. The outcome is reported as the proportion of patients who remain event-free at 2 years.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 years	For patients who have died, overall survival is calculated in months from the day of registration to date of death. Otherwise, overall survival is censored at the last day the patient is known alive (LKA). The outcome is reported as the proportion of patients who remain alive at 2 years.
Local-regional Control	2 years	Local-regional control is defined as the time from the date of registration to the date of any of the following, whichever comes first: * Surgery of primary tumour at any time performed for clinical or radiological disease persistence/progression/recurrence with tumour present/unknown on final pathology. * Neck dissection \> 20 weeks from the end of radiation therapy performed for clinical or radiological (RECIST 1.1) disease persistence/progression/recurrence within target volumes with tumour present/unknown on final pathology. * Neck dissection at any time after registration performed for clinical or radiological disease recurrence/progression outside the target volumes or without documentation of the site of failure with tumour present/unknown on final pathology. * the first record of appearance (radiological or clinical) of local or regional disease progression. The outcome is reported as the proportion of patients who remain local-regional control free at 2 years.
Out-of-field Regional Control	2 years	Time to out-of-field regional failure is defined as the time from the date of registration to the date of the first record of appearance of regional progression/recurrence outside the treatment field , or to the date of neck dissection at any time after registration with tumour present/unknown performed for clinical or radiological disease progression outside the target volumes whichever comes first. The outcome is reported as the proportion of patients who remain out-of-field regional control free at 2 years.
Distant Metastasis Free Survival	2 years	Distant metastasis free survival is defined as the time from the date of registration to the date of first record of appearance of distant metastasis or death for any cause. Local-regional failure or second cancers diagnosed before the distant metastases are not considered events of interest for this endpoint. Subjects alive and free of distant metastasis are censored at the date of the most recent follow-up examination. The outcome is reported as the proportion of patients who remain distant metastasis event-free at 2 years.

Trial Locations

Locations (14): BCCA - Centre for the North
🇨🇦
Prince George, British Columbia, Canada
BCCA - Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
Dr. H. Bliss Murphy Cancer Centre
🇨🇦
St. John's, Newfoundland and Labrador, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦
Hamilton, Ontario, Canada
Kingston Health Sciences Centre
🇨🇦
Kingston, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦
Ottawa, Ontario, Canada
Odette Cancer Centre
🇨🇦
Toronto, Ontario, Canada
University Health Network
🇨🇦
Toronto, Ontario, Canada
The Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
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BCCA - Centre for the North
🇨🇦Prince George, British Columbia, Canada