Ignite Creation Date:
2025-12-24 @ 7:16 PM
Ignite Modification Date:
2026-03-28 @ 10:09 AM
Study NCT ID:
NCT03210103
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-10-05
First Post:
2017-06-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009959', 'term': 'Oropharyngeal Neoplasms'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}], 'ancestors': [{'id': 'D010610', 'term': 'Pharyngeal Neoplasms'}, {'id': 'D010039', 'term': 'Otorhinolaryngologic Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010608', 'term': 'Pharyngeal Diseases'}, {'id': 'D009057', 'term': 'Stomatognathic Diseases'}, {'id': 'D010038', 'term': 'Otorhinolaryngologic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D011827', 'term': 'Radiation'}, {'id': 'D004358', 'term': 'Drug Therapy'}, {'id': 'D037981', 'term': 'Neck Dissection'}], 'ancestors': [{'id': 'D055585', 'term': 'Physical Phenomena'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D008197', 'term': 'Lymph Node Excision'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D013517', 'term': 'Otorhinolaryngologic Surgical Procedures'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '2 Arm study randomized in a 1:1 ratio'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 61}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2018-01-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-10', 'completionDateStruct': {'date': '2028-08-15', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-10-04', 'studyFirstSubmitDate': '2017-06-28', 'studyFirstSubmitQcDate': '2017-07-04', 'lastUpdatePostDateStruct': {'date': '2023-10-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-07-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-08-15', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Overall Survival', 'timeFrame': '2 years', 'description': 'Time from randomization to death from any cause'}], 'secondaryOutcomes': [{'measure': 'Quality of Life 1 year post treatment', 'timeFrame': '1 year post treatment', 'description': 'Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)'}, {'measure': 'Progression free survival comparison with historical controls', 'timeFrame': '5 years', 'description': 'Defined as time from randomization to death from any cause'}, {'measure': 'Quality of life', 'timeFrame': 'Baseline to 5 years follow up', 'description': 'Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)'}, {'measure': 'Quality of life', 'timeFrame': 'Baseline to 5 years follow up', 'description': 'Quality of Life using the following questionnaire: EORTC QLQ C30'}, {'measure': 'Quality of life', 'timeFrame': 'Baseline to 5 years follow up', 'description': 'Quality of Life using the following questionnaire: H\\&N35 scale'}, {'measure': 'Quality of life', 'timeFrame': 'Baseline to 5 years follow up', 'description': 'Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)'}, {'measure': 'Quality of life', 'timeFrame': 'Baseline to 5 years follow up', 'description': 'Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)'}, {'measure': 'Quality of life', 'timeFrame': 'Baseline to 5 years follow up', 'description': 'Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)'}, {'measure': 'toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4', 'timeFrame': 'Randomization until 5 years follow up', 'description': 'To determine to toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4'}, {'measure': 'Feeding tube rate at 1 year', 'timeFrame': 'baseline to 1 year post treatment', 'description': 'Measure other functional measurements such as feeding tube rate at 1 year'}, {'measure': 'CTCAE Dysphagia grade', 'timeFrame': 'baseline to 5 years post treatment', 'description': 'Measure other functional measurements such as CTCAE Dysphagia grade'}, {'measure': 'Speech intelligibility', 'timeFrame': 'baseline to 5 years post treatment', 'description': 'Measure other functional measurements such as speech intelligibility'}, {'measure': 'Normalcy of diet', 'timeFrame': 'baseline to 5 years post treatment', 'description': 'Measure other functional measurements such as normalcy of diet'}, {'measure': '2 year progression-free survival comparison between Arm 1 and Arm 2', 'timeFrame': '2 years', 'description': 'Time from randomization to disease progress at any site or death from any cause'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Transoral Surgery', 'Head and Neck Cancer'], 'conditions': ['Oropharyngeal Cancer']}, 'referencesModule': {'references': [{'pmid': '40121836', 'type': 'DERIVED', 'citation': "Palma DA, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Eskander A, Higgins K, Karam I, Poon I, Husain Z, Enepekides D, Hier M, Richardson K, Mlynarek A, Johnson-Obaseki S, Gaudet M, Bayley A, Dowthwaite S, Jackson JE, Dzienis M, O'Neil J, Chandarana S, Banerjee R, Hart R, Chung J, Tenenholtz T, Le H, Yoo J, Mendez A, Winquist E, Kuruvilla S, Stewart P, Warner A, Mitchell S, Chen J, Parker C, Kwan K, Theurer J, Bahig H, Christopoulos A, Mendez LC, Sathya J, Hammond JA, Read N, Venkatesan V, Fung K, Nichols AC. Radiation vs. trans-oral surgery for treatment de-escalation in HPV-related oropharyngeal cancers: Primary analysis of the ORATOR2 randomized trial. Eur J Cancer. 2025 May 2;220:115343. doi: 10.1016/j.ejca.2025.115343. Epub 2025 Mar 10."}, {'pmid': '35482348', 'type': 'DERIVED', 'citation': "Palma DA, Prisman E, Berthelet E, Tran E, Hamilton S, Wu J, Eskander A, Higgins K, Karam I, Poon I, Husain Z, Enepekides D, Hier M, Sultanem K, Richardson K, Mlynarek A, Johnson-Obaseki S, Odell M, Bayley A, Dowthwaite S, Jackson JE, Dzienis M, O'Neil J, Chandarana S, Banerjee R, Hart R, Chung J, Tenenholtz T, Krishnan S, Le H, Yoo J, Mendez A, Winquist E, Kuruvilla S, Stewart P, Warner A, Mitchell S, Chen J, Parker C, Wehrli B, Kwan K, Theurer J, Sathya J, Hammond JA, Read N, Venkatesan V, MacNeil SD, Fung K, Nichols AC. Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2022 Jun 1;8(6):1-7. doi: 10.1001/jamaoncol.2022.0615."}, {'pmid': '32059705', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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', 'detailedDescription': '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\n\nThe 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.\n\nThe 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)\n\nPatients will be followed for a total of 5 years'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 18 years or older\n* willing to provide informed consent\n* ECOG performance status 0-2\n* Histologically confirmed squamous cell carcinoma\n* P16 positive, or HPV positive\n* Primary tumor site in the oropharynx (includes tonsil, soft palate, base of tongue, walls of oropharynx)\n* 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.\n* Smokers and non-smokers are included. Patients will be stratified by ,\\<10 pack years smoking history versus \\> or equal to 10 pack years.\n* Tumor stage (AJCC 8th edition): T1 or T2\n* Nodal stage (AJCC 8th edition): N0, N1, or N2\n* 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\n* patients assessed at head and neck multidisciplinary clinic (with assessment by radiation oncologist and surgeon) and presented at multidisciplinary tumor board prior to randomization\n\nExclusion Criteria:\n\n* 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\n* Serious medical comorbidities or other contraindications to radiotherapy, chemotherapy or surgery\n* prior history of head and neck cancer within 5 years\n* prior head and neck radiation at any time\n* metastatic disease\n* inability to attend full course of radiotherapy or follow up visits\n* prior invasive malignant disease unless disease-free for at least 5 years or more, with the exception of non-melanoma skin cancer\n* pregnant or lactating women'}, 'identificationModule': {'nctId': 'NCT03210103', 'acronym': 'ORATOR2', 'briefTitle': 'Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer', 'organization': {'class': 'OTHER', 'fullName': "London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's"}, 'officialTitle': 'A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)', 'orgStudyIdInfo': {'id': 'ORATOR2'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Arm 1, Radiation +/- Chemotherapy', 'description': 'Standard Treatment (Radiation +/- Chemotherapy)', 'interventionNames': ['Radiation: Radiation']}, {'type': 'EXPERIMENTAL', 'label': 'Arm 2, TOS + Neck Dissection', 'description': 'Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)', 'interventionNames': ['Procedure: Transoral Surgery (TOS) + Neck Dissection']}], 'interventions': [{'name': 'Radiation', 'type': 'RADIATION', 'otherNames': ['Chemotherapy, if required'], 'description': 'Standard of Care: Radiation +/- Chemotherapy', 'armGroupLabels': ['Arm 1, Radiation +/- Chemotherapy']}, {'name': 'Transoral Surgery (TOS) + Neck Dissection', 'type': 'PROCEDURE', 'otherNames': ['Radiation, if required'], 'description': 'Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)', 'armGroupLabels': ['Arm 2, TOS + Neck Dissection']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Gold Coast', 'state': 'Queensland', 'country': 'Australia', 'facility': 'Gold Coast University Hospital', 'geoPoint': {'lat': -28.00029, 'lon': 153.43088}}, {'city': 'Adelaide', 'country': 'Australia', 'facility': 'Royal Adelaide Hospital', 'geoPoint': {'lat': -34.92866, 'lon': 138.59863}}, {'zip': 'T2N 4N2', 'city': 'Calgary', 'state': 'Alberta', 'country': 'Canada', 'facility': 'Tom Baker Cancer Centre', 'geoPoint': {'lat': 51.05011, 'lon': -114.08529}}, {'zip': 'V5Z 1G1', 'city': 'Vancouver', 'state': 'British Columbia', 'country': 'Canada', 'facility': 'BC Cancer', 'geoPoint': {'lat': 49.24966, 'lon': -123.11934}}, {'zip': 'N6A 4L6', 'city': 'London', 'state': 'Ontario', 'country': 'Canada', 'facility': 'London Regional Cancer Program', 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}, {'zip': 'K1Y 4E9', 'city': 'Ottawa', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Ottawa Hospital Research Institute', 'geoPoint': {'lat': 45.41117, 'lon': -75.69812}}, {'zip': 'M4N 3M5', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Sunnybrook Research Institute', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': 'M5G 2C4', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'University Health Network', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': 'H3T 1E2', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Jewish General Hospital', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}], 'overallOfficials': [{'name': 'David Palma', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's"}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's", 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}