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Stereotactic Boost and Short-course Radiation Therapy for Oropharynx Cancer (SHORT-OPC)

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ClinicalTrials.gov Identifier: NCT04178174
Recruitment Status : Recruiting
First Posted : November 26, 2019
Last Update Posted : February 21, 2021
Sponsor:
Collaborators:
M.D. Anderson Cancer Center
Lawson Health Research Institute
Jewish General Hospital
Information provided by (Responsible Party):
Houda Bahig, Centre hospitalier de l'Université de Montréal (CHUM)

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.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Oropharynx Cancer Human Papilloma Virus Radiation: SABR boost and de-escalated chemoradiation Radiation: Standard chemoradiation Phase 2

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Stereotactic Boost and SHOrt-course Radiation Therapy for HPV-associated OroPharynx Cancer Trial: A Randomized Multicentric Phase II Trial
Actual Study Start Date : February 23, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2025

Arm Intervention/treatment
Experimental: SABR boost and de-escalated chemoradiation
SABR boost of 14 Gy in 2 fractions to the GTV, immediately followed by de-escalated chemoradiation. De-escalated chemoradiation will consist in 40 Gy in 20 fractions with concurrent high dose Cisplatin (3-weekly, 100 mg/m2) for 2 cycles, aiming for a cumulative dose of 200 mg/m2.
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

Active Comparator: Standard chemoradiation
The standard arm will consist of conventionally radiation to a dose of 70 Gy in 33 fractions concurrently with high dose Cisplatin (3-weekly, 100 mg/m2) for 2-3 cycles, aiming for a cumulative dose of ≥ 200 mg/m2.
Radiation: Standard chemoradiation
Standard Cisplatin-based chemoradiation to a dose of 70 Gy in 33 fractions




Primary Outcome Measures :
  1. Locoregional control [ Time Frame: 2 years after the end of chemoradiation ]
    Patient alive with locoregional control at 2 years after the end of chemoradiation


Secondary Outcome Measures :
  1. Subacute toxicity [ Time Frame: Between 2 and 6 months after the end of chemoradiation ]
    Rate of grade ≥ 3 subacute toxicity

  2. Acute toxicity [ Time Frame: Less than 2 months after the end of chemoradiation ]
    Rate of grade ≥ 3 acute toxicity

  3. Late toxicity [ Time Frame: Between 6 months and 5-years after the end of chemoradiation ]
    Rate of grade ≥ 3 late toxicity

  4. OS [ Time Frame: At 2- and 5-years after the end of chemoradiation ]
    Overall survival

  5. PFS [ Time Frame: At 2- and 5-years after the end of chemoradiation ]
    Progression free survival

  6. Head and neck symptom burden [ Time Frame: 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.

  7. Dysphagia [ Time Frame: 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.

  8. Time from treatment start to return to work [ Time Frame: Measured in days and reported at 2-years post-treatment ]
    Time from first day of treatment start to first day of return to work.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04178174


Contacts
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Contact: Diane Trudel 514-890-8254 diane.dt.chum@ssss.gouv.qc.ca

Locations
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Canada, Quebec
Centre Hospitalier de l'Université de Montréal Recruiting
Montreal, Quebec, Canada, H2X 1R6
Contact: Mom Phat    514-890-8000 ext 26906    mom.phat.chum@ssss.gouv.qc.ca   
Principal Investigator: Houda Bahig         
Sub-Investigator: Phuc-Félix Nguyen-Tan         
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
M.D. Anderson Cancer Center
Lawson Health Research Institute
Jewish General Hospital
Investigators
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Study Chair: Houda Bahig, MD PhD Centre hospitalier de l'Université de Montréal (CHUM)
Study Chair: Phuc-Felix Nguyen-Tan, MD Centre hospitalier de l'Université de Montréal (CHUM)
Principal Investigator: David Palma, MD PhD Lawson Health Research Institute
Principal Investigator: Jack Phan, MD PhD M.D. Anderson Cancer Center
Principal Investigator: Khalil Sultanem, MD Montreal Jewish General Hospital
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Responsible Party: Houda Bahig, Radiation Oncologist, Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT04178174    
Other Study ID Numbers: CentreHUM
First Posted: November 26, 2019    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Houda Bahig, Centre hospitalier de l'Université de Montréal (CHUM):
head and neck cander
Oropharynx cancer
Human papilloma virus
Radiotherapy
Stereotactic body radiotherapy
Chemotherapy
De-intensification
Additional relevant MeSH terms:
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Papilloma
Oropharyngeal Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases