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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 : August 14, 2020
Sponsor:
Information provided by (Responsible Party):
Lawson Health Research Institute

Tracking Information
First Submitted Date  ICMJE June 28, 2017
First Posted Date  ICMJE July 6, 2017
Last Update Posted Date August 14, 2020
Actual Study Start Date  ICMJE January 26, 2018
Estimated Primary Completion Date August 15, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
Overall Survival [ Time Frame: 2 years ]
Time from randomization to death from any cause
Original Primary Outcome Measures  ICMJE
 (submitted: July 4, 2017)
2 year progression free survival [ Time Frame: 2 years ]
Time from randomization to disease progress at any site or death from any cause
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2019)
  • 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)
  • Progression free survival comparison with historical controls [ Time Frame: 5 years ]
    Defined as time from randomization to death from any cause
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: EORTC QLQ C30
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: H&N35 scale
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
  • 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
  • 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
  • CTCAE Dysphagia grade [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as CTCAE Dysphagia grade
  • Speech intelligibility [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as speech intelligibility
  • Normalcy of diet [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as normalcy of diet
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 4, 2017)
  • 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)
  • Overall Survival [ Time Frame: 5 years ]
    Defined as time from randomization to death from any cause
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: EORTC QLQ C30
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: H&N35 scale
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)
  • Quality of life [ Time Frame: Baseline to 5 years follow up ]
    Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)
  • 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
  • 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
  • CTCAE Dysphagia grade [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as CTCAE Dysphagia grade
  • Speech intelligibility [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as speech intelligibility
  • Normalcy of diet [ Time Frame: baseline to 5 years post treatment ]
    Measure other functional measurements such as normalcy of diet
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer
Official Title  ICMJE A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)
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
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Oropharyngeal Cancer
Intervention  ICMJE
  • Radiation: Radiation
    Standard of Care: Radiation +/- Chemotherapy
    Other Name: Chemotherapy, if required
  • Procedure: Transoral Surgery (TOS) + Neck Dissection
    Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
    Other Name: Radiation, if required
Study Arms  ICMJE
  • Active Comparator: Arm 1, Radiation +/- Chemotherapy
    Standard Treatment (Radiation +/- Chemotherapy)
    Intervention: Radiation: Radiation
  • Experimental: Arm 2, TOS + Neck Dissection
    Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)
    Intervention: Procedure: Transoral Surgery (TOS) + Neck Dissection
Publications * Nichols AC, Lang P, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Fung K, de Almeida JR, Bayley A, Goldstein DP, Eskander A, Husain Z, Bahig H, Christopoulous A, Hier M, Sultanem K, Richardson K, Mlynarek A, Krishnan S, Le H, Yoo J, MacNeil SD, Mendez A, Winquist E, Read N, Venkatesan V, Kuruvilla S, Warner A, Mitchell S, Corsten M, Rajaraman M, Johnson-Obaseki S, Eapen L, Odell M, Chandarana S, Banerjee R, Dort J, Matthews TW, Hart R, Kerr P, Dowthwaite S, Gupta M, Zhang H, Wright J, Parker C, Wehrli B, Kwan K, Theurer J, Palma DA. Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial. BMC Cancer. 2020 Feb 14;20(1):125. doi: 10.1186/s12885-020-6607-z.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2019)
140
Original Estimated Enrollment  ICMJE
 (submitted: July 4, 2017)
120
Estimated Study Completion Date  ICMJE August 15, 2028
Estimated Primary Completion Date August 15, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Susan Archer 519-685-8618 susan.archer@lhsc.on.ca
Listed Location Countries  ICMJE Australia,   Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03210103
Other Study ID Numbers  ICMJE ORATOR2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Lawson Health Research Institute
Study Sponsor  ICMJE Lawson Health Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Palma Lawson Health Research Institute
PRS Account Lawson Health Research Institute
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP