HYperfractionated Radiation Therapy Versus Concurrent Chemoradiation for Head and Neck Cancer (HYTC)
HYperfractionated Radiation Therapy Versus Concurrent Chemoradiation for Head and Neck Cancer (HYTC): A Phase III Randomized Controlled Trial
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Issa Mohamad, Radiation oncologist
- Phone Number: 0799825592
- Email: imohamad@KHCC.JO
Study Contact Backup
- Name: Ali Hosni, Radiation Onclogsit
- Phone Number: +16478951225
- Email: ali.hosni@uhn.ca
Study Locations
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Amman, Jordan, 11941
- Recruiting
- King Hussein Cancer Center
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Contact:
- Issa Mohamad, Radiation oncologist
- Phone Number: 00962799825592
- Email: imohamad@khcc.jo
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Contact:
- Lina Alelaumi, PharmD
- Phone Number: 00962796420055
- Email: LA.17435@KHCC.JO
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Principal Investigator:
- Issa Mohamad, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria: Patients with pathologically (histologically or cytologically) proven diagnosis of HNSCC (larynx, hypopharynx, or oropharynx). Pathologic confirmation may be from either nodal or primary tumour. If a biopsy is obtained from nodal disease, a clinically apparent primary tumour on imaging and/or clinical examination must be present.
Diagnostic tonsillectomy or local excision of the primary without removal of nodal disease is permitted.
Diagnostic lymph node excision or limited neck dissections (retrieving ≤ 4 nodes) are permitted HPV positive or negative (by p16 immunohistochemistry). OPC will be classified as p16 at local sites based on greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining.
For patients with OPC: analysis of p16 status is required For patients with laryngeal/hypopharyngeal cancer: analysis of p16 status is NOT required
Clinical stage T1-2 N1-2 M0 or T3 N0-2 M0 (UICC/AJCC TNM 8th Edition). Staging will be determined based on clinical examination, axial imaging (CT and/or MRI), and whenever available, PET-CT imaging.
The following radiological investigations must be done within 8 weeks of registration:
CT or MRI of the head and neck; PET-CT scan or chest CT scan (PET-CT scan is strongly preferred and highly recommended to be used for eligibility).
Planned definitive RT. Based on clinical and laboratory evaluation and in keeping with local institutional standards, the treating oncologist must declare upfront, that in the absence of the present clinical trial, the patient would be candidate for treatment with concurrent high dose cisplatin every 3 weeks. This would include:
Adequate hematologic function must be documented within 8 weeks prior to registration:
Hemoglobin levels of > 8g/dL (the use of transfusion or other intervention to achieve hemoglobin ≥ 8 g/dL is acceptable) Platelet count of >100,000 cells/mm3. ANC of > 1500 cells/mm3.
Adequate hepatic function must be documented within 8 weeks prior to registration:
Total bilirubin < 2 X institutional upper limit of normal. AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal. Albumin ≥ 3.0 g/dL.
Adequate renal function must be documented within 8 weeks prior to registration:
Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula
Patients known to be Human Immunodeficiency Virus (HIV)+ are permitted.
Patients with CD4>200 and serum HIV viral load of < 200 copies/mm3 are eligible
HIV+ patients must receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management.
HIV testing is not required for eligibility. Must be ≥ 18 years of age.
Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
Patient is able (i.e. sufficiently fluent) and willing to complete the PRO questionnaires in English or Arabic. The baseline assessment must be completed within required timelines, prior to treatment start. Inability (lack of comprehension in English/Arabic, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study.
Consent to provision of samples of blood and plasma for correlative studies is optional.
The treatment team must be able to commence definitive RT within 6 weeks of randomization.
Women of child bearing potential must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 6 months after the last day of RT. Sexually active males must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 6 months after the last day of RT.
Women must not be pregnant or breast-feeding (Women in childbearing period will be instructed by treating physician to avoid pregnancy during and 6 months after end of RT). All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 4 weeks prior to registration. All breastfeeding women should discontinue breastfeeding prior to study registration.
Participants must not be receiving any other standard anti-cancer therapy or experimental agent concurrently with the study drugs.
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Exclusion Criteria:Patients who fulfill any of the following criteria are not eligible for admission to the study:
HNC Patients with any of the following clinical stages/categories:
cT1-2 N0 M0 cT4 cN3 cM1
Patients with primary oral cavity cancer, nasopharynx cancer, or HNC of unknown primary.
Previous HNC or multiple synchronous primary HNCs.
Previous induction or neo-adjuvant chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable, however, any prior exposure to cisplatin is excluded.
Previous RT to the head and neck or neck dissection of at least 3 levels on either side.
Patients with severe, active co-morbidity including any of the following:
Chronic obstructive pulmonary disease or other pulmonary illness requiring hospitalization within 30 days of registration Unstable angina and/or congestive heart failure requiring hospitalization within 6 months of registration Acute myocardial infarction within 6 months of study registration Diseases precluding RT (e.g. scleroderma) Persistent grade 3-4 (CTCAE v5) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing Active infection requiring IV antibiotics prior to registration; Chronic renal disease e.g., nephrotic syndrome, that could be worsened by cisplatin therapy History of allogenic organ transplantation Any symptomatic peripheral sensory neuropathy grade ≥ 2 (CTCAE v5)
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
Prior allergic reaction to cisplatin
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Active Comparator: concurrent Chemoradiation
concurrent chemoradiation with high dose cisplatin (Arm A) ) in patients with head and neck squamous cell carcinoma
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70 Gy 35 fractions/7weeks+high dose of cisplatin
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Experimental: hyperfractionated radiation therapy
hyperfractionated radiation therapy 81.6 Gy
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81.6 Gy /68 fractions BID FOR 7 WEEKS
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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OVERALL SURVIVAL
Time Frame: 7 YEARS
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To determine if hyperfractionated radiation therapy (Arm B) has a non-inferior overall survival (OS) compared to concurrent chemoradiation (CRT) with high dose cisplatin every 3 weeks (Arm A) in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC).
|
7 YEARS
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Oncologic outcomes
Time Frame: 7 YEARS
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To compare between arms the following: Oncologic outcomes: loco-regional failure (LRF) |
7 YEARS
|
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Change in hearing threshold levels as assessed by pure tone audiometry
Time Frame: 7 YEARS
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Hearing threshold levels will be measured using pure tone audiometry across standard audiometric frequencies.
Changes from baseline hearing thresholds will be assessed and compared between study groups
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7 YEARS
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Treatment-related toxicity/adverse events
Time Frame: 7 YEARS
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Treatment-related toxicity/adverse events: physician-assessed toxicities: National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) v.5
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7 YEARS
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Change from baseline in Head and Neck Cancer-specific quality of life as assessed by the University of Washington Quality of Life Questionnaire
Time Frame: 7 YEARS
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Patient-reported quality of life and swallowing-related quality of life will be assessed using the University of Washington Quality of Life Questionnaire (UW-QOL) .
Questionnaire with higher scores indicating better quality of life and swallowing function.
Change from baseline scores will be evaluated at predefined study time points
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7 YEARS
|
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Distant metastasis (DM) rate between treatment arms
Time Frame: From randomisation till 7 years for each study participant
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he occurrence of distant metastases will be assessed and compared between study arms during the study follow-up period
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From randomisation till 7 years for each study participant
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disease-free survival (DFS)
Time Frame: 7 years
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Disease-free survival (DFS) will be defined as the time from randomization to the first occurrence of disease recurrence (local, regional, or distant) or death from any cause, whichever occurs first
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7 years
|
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Change from baseline in ototoxicity severity as assessed by the Modified TUNE grading scale
Time Frame: 7 years
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Ototoxicity severity will be evaluated using the Modified TUNE grading scale.
The scale grades hearing impairment severity based on audiologic assessment findings.
Changes from baseline grading scores will be assessed and compared at predefined study time points, with higher grades indicating worse ototoxicity.
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7 years
|
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Change from baseline in speech recognition as assessed by Consonant-Nucleus-Consonant (CNC) word scores
Time Frame: 7 years
|
Speech recognition ability will be evaluated using speech audiometry with Consonant-Nucleus-Consonant (CNC) word testing.
CNC word scores will be reported as the percentage of correctly identified words, with higher scores indicating better speech recognition performance.
Changes from baseline scores will be assessed at predefined study time points
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7 years
|
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Number of participants with abnormal tympanometry findings
Time Frame: 7 years
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Tympanometry will be performed to assess middle ear function.
Tympanogram results will be classified according to standard tympanogram types, and the number of participants with abnormal findings will be reported at predefined study time points.
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7 years
|
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Treatment-related toxicity/adverse events-PRO
Time Frame: 7 years
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Treatment-related toxicity/adverse events: patient-reported toxicity: Patient Reported Outcomes - Common Terminology Criteria of Adverse Events (PRO CTCAE) v1.
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7 years
|
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Patient-reported outcomes (PRO):UW-QOL
Time Frame: 7 years
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Patient-reported outcomes (PRO): instrument [University of Washington Quality of Life Questionnaire (UW-QOL)]
|
7 years
|
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Patient-reported outcomes (PRO): MDADI
Time Frame: 7 Years
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swallowing-related PRO [M.D. Anderson Dysphagia Inventory (MDADI)]
|
7 Years
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Change from baseline in Head and Neck Cancer-specific quality of life as assessed by the M. D. Anderson Dysphagia Inventory (MDADI)
Time Frame: 7 years
|
Patient-reported quality of life and swallowing-related quality of life will be assessed using the M. D. Anderson Dysphagia Inventory (MDADI).
Questionnaire with higher scores indicating better quality of life and swallowing function.
Change from baseline scores will be evaluated at predefined study time points
|
7 years
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 23 KHCC 141
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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