Stereotactic Boost and Short-course Radiation Therapy for Oropharynx Cancer

Head and Neck Cancer Clinical Trial

— SHORT-OPC  

Official title:

Stereotactic Boost and SHOrt-course Radiation Therapy for HPV-associated OroPharynx Cancer Trial: A Randomized Multicentric Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04178174
• Other study ID #: SHORT-OPC
• Status: Recruiting
• Phase: Phase 2
• Start date: February 23, 2020
• Est. completion date: December 2026

Study information

• Verified date: December 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: Diane Trudel
• Phone: 514-890-8254
• Email: diane.dt.chum[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 II trial with 2 planned interim safety (toxicity) analysis and 1 futility (locoregional control) analysis with go/no go decision to pursue the study based on probabilities of toxicities and LRC (Bayesian adaptive design). Patients will be randomized using a 1:1 ratio between the standard and the experimental arm and will be stratified by tumor stage. At the significance level of 0.2 and assuming the LRC rate of 90% for both experimental and control arms, 80% for the non-inferiority test with the margin of 10%, and 6% attrition rate, a total of 106 patients will be enrolled.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

• Previous irradiation of the head and neck (HNC) 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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Human Papilloma Virus
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Papilloma

Intervention

Radiation:
• SABR 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
• Standard chemoradiation
Standard Cisplatin-based chemoradiation to a dose of 70 Gy in 33 fractions

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal	Montreal	Quebec

Sponsors (4)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)	Jewish General Hospital, Lawson Health Research Institute, M.D. Anderson Cancer Center

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Locoregional control	Patient alive with locoregional control at 2 years after the end of chemoradiation	2 years after the end of chemoradiation
Secondary	Subacute toxicity	Rate of grade = 3 subacute toxicity	Between 2 and 6 months after the end of chemoradiation
Secondary	Acute toxicity	Rate of grade = 3 acute toxicity	Less than 2 months after the end of chemoradiation
Secondary	Late toxicity	Rate of grade = 3 late toxicity	Between 6 months and 5-years after the end of chemoradiation
Secondary	OS	Overall survival	At 2- and 5-years after the end of chemoradiation
Secondary	PFS	Progression free survival	At 2- and 5-years after the end of chemoradiation
Secondary	Head and neck symptom burden	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.	At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation
Secondary	Dysphagia	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.	At baseline, and 1-, 3-, 6-, 12- months post-treatment, and yearly from years 2-5 after the end of chemoradiation
Secondary	Time from treatment start to return to work	Time from first day of treatment start to first day of return to work.	Measured in days and reported at 2-years post-treatment