Clinical trial NCT03210103: Primary Radiotherapy Versus Primary Surgery for HPV-Associated Oropharyngeal Cancer
Official title: A Randomized Trial of Treatment De-Escalation for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: Radiotherapy vs. Trans-Oral Surgery (ORATOR II)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Oropharyngeal Cancer
Keywords: Transoral Surgery
Head and Neck Cancer
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2017-07-06
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 Arm study randomized in a 1:1 ratio
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Overall Survival
timeFrame: 2 years
Secondary outcomes:
measure: Quality of Life 1 year post treatment
timeFrame: 1 year post treatment
measure: Progression free survival comparison with historical controls
timeFrame: 5 years
measure: Quality of life
timeFrame: Baseline to 5 years follow up
measure: Quality of life
timeFrame: Baseline to 5 years follow up
measure: Quality of life
timeFrame: Baseline to 5 years follow up
measure: Quality of life
timeFrame: Baseline to 5 years follow up
measure: Quality of life
timeFrame: Baseline to 5 years follow up
measure: Quality of life
timeFrame: Baseline to 5 years follow up
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
measure: Feeding tube rate at 1 year
timeFrame: baseline to 1 year post treatment
measure: CTCAE Dysphagia grade
timeFrame: baseline to 5 years post treatment
measure: Speech intelligibility
timeFrame: baseline to 5 years post treatment
measure: Normalcy of diet
timeFrame: baseline to 5 years post treatment
measure: 2 year progression-free survival comparison between Arm 1 and Arm 2
timeFrame: 2 years
Other outcomes:
Locations:
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: David Palma
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.