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Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer (ORATOR2)

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ClinicalTrials.gov Identifier: NCT03210103
Recruitment Status : Recruiting
First Posted : July 6, 2017
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Lawson Health Research Institute

Brief Summary:
The goal of this randomized treatment de-escalation study is to formally compare outcomes in HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary surgical approach, to provide a high level of evidence to guide the selection of treatment options for a subsequent phase III trial

Condition or disease Intervention/treatment Phase
Oropharyngeal Cancer Radiation: Radiation Procedure: Transoral Surgery (TOS) + Neck Dissection Not Applicable

Detailed Description:

The goal of this randomized treatment de-escalation study is to formally compare outcomes in HPV related oropharyngeal cancer tumors treated with a primary radiotherapy versus a primary surgical approach, to provide a high level of evidence to guide the selection of treatment options for a subsequent phase III trial

The study will compare overall survival rates relative to historical controls for de-intensified primary radiotherapy [60 GY +/- chemotherapy] versus transoral surgery (TOS) and neck dissection [+/- adjuvant 50Gy radiotherapy] in patients with early T-stage HPV-positive squamous cell carcinoma of the oropharynx and to compare quality of life (QOL) profiles.

The study will require a sample size of 140 patients randomized in a 1:1 ratio between the two arms. Arm 1 (radiotherapy +/1 chemotherapy) and Arm 2 (TOS)

Patients will be followed for a total of 5 years


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2 Arm study randomized in a 1:1 ratio
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)
Actual Study Start Date : January 26, 2018
Estimated Primary Completion Date : August 15, 2028
Estimated Study Completion Date : August 15, 2028

Arm Intervention/treatment
Active Comparator: Arm 1, Radiation +/- Chemotherapy
Standard Treatment (Radiation +/- Chemotherapy)
Radiation: Radiation
Standard of Care: Radiation +/- Chemotherapy
Other Name: Chemotherapy, if required

Experimental: Arm 2, TOS + Neck Dissection
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Procedure: Transoral Surgery (TOS) + Neck Dissection
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
Other Name: Radiation, if required




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 2 years ]
    Time from randomization to death from any cause


Secondary Outcome Measures :
  1. Quality of Life 1 year post treatment [ Time Frame: 1 year post treatment ]
    Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)

  2. Progression free survival comparison with historical controls [ Time Frame: 5 years ]
    Defined as time from randomization to death from any cause

  3. Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)

  4. Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: EORTC QLQ C30

  5. Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: H&N35 scale

  6. Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)

  7. Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)

  8. Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)

  9. toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4 [ Time Frame: Randomization until 5 years follow up ]
    To determine to toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4

  10. Feeding tube rate at 1 year [ Time Frame: baseline to 1 year post treatment ]
    Measure other functional measurements such as feeding tube rate at 1 year

  11. CTCAE Dysphagia grade [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as CTCAE Dysphagia grade

  12. Speech intelligibility [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as speech intelligibility

  13. Normalcy of diet [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as normalcy of diet

  14. 2 year progression-free survival comparison between Arm 1 and Arm 2 [ Time Frame: 2 years ]
    Time from randomization to disease progress at any site or death from any cause



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 or older
  • willing to provide informed consent
  • ECOG performance status 0-2
  • Histologically confirmed squamous cell carcinoma
  • P16 positive, or HPV positive
  • Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx)
  • Eligible for curative intent treatment, with likely negative resection margins at surgery. For patients where adequate transoral access is in question, they will first undergo an examination under anesthesia prior to randomization to ensure adequate exposure can be obtained.
  • Smokers and non-smokers are included. Patients will be stratified by ,<10 pack years smoking history versus > or equal to 10 pack years.
  • Tumor stage (AJCC 8th edition): T1 or T2
  • Nodal stage (AJCC 8th edition): N0, N1, or N2
  • For patients who may require chemotherapy (ie, patients with multiple lymph nodes positive or a single node more than 3 cm in size, in any plane, CBC/differential within 4 weeks prior to randomization with adequate bone marrow function, hepatic, and renal function defined as: Hemoglobin ≥ 80 g/L; Absolute neutrophil count ≥ 1.5 x 10 9/L, platelets ≥ 100 x 10 9/L, bilirubin ≤ 35 umol/L, AST or ALT ≤ 3 x the upper limit of normal; serum creatinine ≤ 130 umol/L or creatinine clearance ≥ 50 ml/min
  • patients assessed at head and neck multidisciplinary clinic (with assessment by radiation oncologist and surgeon) and presented at multidisciplinary tumor board prior to randomization

Exclusion Criteria:

  • unambiguous clinical or radiological evidence of extranodaal extension on pre-treatment imaging. This includes the presence of matted notes, defined as 3 or more nodes that are abutting with loss of intervening fat planes
  • Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy or surgery
  • prior history of head and neck cancer within 5 years
  • prior head and neck radiation at any time
  • metastatic disease
  • inability to attend full course of radiotherapy or follow up visits
  • prior invasive malignant disease unless disease-free for at least 5 years or more, with the exception of non-melanoma skin cancer
  • pregnant or lactating women

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): NCT03210103


Contacts
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Contact: Susan Archer 519-685-8618 susan.archer@lhsc.on.ca

Locations
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Canada, British Columbia
BC Cancer Recruiting
Vancouver, British Columbia, Canada, V5Z 1G1
Contact: Eric Berthelet, MD    604-877-6000    eberthelet@bccancer.bc.ca   
Canada, Ontario
London Regional Cancer Program Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Susan Archer    519-685-8618    susan.archer@lhsc.on.ca   
Contact: David Palma    519-685-8500    David.Palma@lhsc.on.ca   
Principal Investigator: David Palma         
Principal Investigator: Anthony Nichols         
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4E9
Contact: Stephanie Johnson-Obaseki, MD    613-737-7700    stjohnson@toh.ca   
Sunnybrook Research Institute Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Antoine Eskander, MD       Antoine.Eskander@sunnybrook.ca   
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: John de Almeida, MD    416-946-2000    John.deAlmeida@uhn.ca   
Canada, Quebec
Jewish General Hospital Recruiting
Montréal, Quebec, Canada, H3T 1E2
Contact: Michael Hier, MD    514-340-8222    mhier@jgh.mcgill.ca   
Sponsors and Collaborators
Lawson Health Research Institute
Investigators
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Principal Investigator: David Palma Lawson Health Research Institute

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Responsible Party: Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT03210103     History of Changes
Other Study ID Numbers: ORATOR2
First Posted: July 6, 2017    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 Lawson Health Research Institute:
Transoral Surgery
Head and Neck Cancer
Additional relevant MeSH terms:
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Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases