Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer

Oropharyngeal Cancer Clinical Trial

— ORATOR2  

Official title:

A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03210103
• Other study ID #: ORATOR2
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 26, 2018
• Est. completion date: August 15, 2028

Study information

• Verified date: October 2023
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 61
• Est. completion date: August 15, 2028
• Est. primary completion date: August 15, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Oropharyngeal Cancer
• Oropharyngeal Neoplasms

Intervention

Radiation:
• Radiation
Standard of Care: Radiation +/- Chemotherapy

Procedure:
• Transoral Surgery (TOS) + Neck Dissection
Transoral Surgery (TOS) + Neck Dissection (plus radiation, if required)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Gold Coast University Hospital	Gold Coast	Queensland
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	BC Cancer	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Countries where clinical trial is conducted

Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Time from randomization to death from any cause	2 years
Secondary	Quality of Life 1 year post treatment	Quality of life 1 year post treatment as assessed with the MD Anderson Dysphagia Inventory (MDADI)	1 year post treatment
Secondary	Progression free survival comparison with historical controls	Defined as time from randomization to death from any cause	5 years
Secondary	Quality of life	Quality of Life using the following questionnaire: MD Anderson Dysphagia Inventory (MDADI)	Baseline to 5 years follow up
Secondary	Quality of life	Quality of Life using the following questionnaire: EORTC QLQ C30	Baseline to 5 years follow up
Secondary	Quality of life	Quality of Life using the following questionnaire: H&N35 scale	Baseline to 5 years follow up
Secondary	Quality of life	Quality of Life using the following questionnaire: Voice Handicap Index (VHI-10)	Baseline to 5 years follow up
Secondary	Quality of life	Quality of Life using the following questionnaire: Neck Dissection Impairment Index (NDII)	Baseline to 5 years follow up
Secondary	Quality of life	Quality of Life using the following questionnaire: Patient Neurotoxicity Questionnaire (PNQ)	Baseline to 5 years follow up
Secondary	toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4	To determine to toxicity profile of both study arms using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 4	Randomization until 5 years follow up
Secondary	Feeding tube rate at 1 year	Measure other functional measurements such as feeding tube rate at 1 year	baseline to 1 year post treatment
Secondary	CTCAE Dysphagia grade	Measure other functional measurements such as CTCAE Dysphagia grade	baseline to 5 years post treatment
Secondary	Speech intelligibility	Measure other functional measurements such as speech intelligibility	baseline to 5 years post treatment
Secondary	Normalcy of diet	Measure other functional measurements such as normalcy of diet	baseline to 5 years post treatment
Secondary	2 year progression-free survival comparison between Arm 1 and Arm 2	Time from randomization to disease progress at any site or death from any cause	2 years