Contact information
Type
Scientific
Primary contact
Dr Charlotte Firth
ORCID ID
Contact details
Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 414 5101
CompARE@trials.bham.ac.uk
Additional identifiers
EudraCT number
2014-003389-26
ClinicalTrials.gov number
NCT04116047
Protocol/serial number
18621
Study information
Scientific title
Phase III randomised controlled trial Comparing Alternative REgimens for escalating treatment of intermediate and high-risk oropharyngeal cancer
Acronym
CompARE
Study hypothesis
Pragmatic phase III open-label randomised controlled trial using an efficient, adaptive, multi-arm multi-stage (MAMS) design, with an integrated qualitative recruitment investigation aiming to optimise recruitment and consenting, to determine the optimum treatment of intermediate and high-risk OPC with the aim of improving survival outcomes without significantly worsening toxicity, Quality of Life (QoL) or swallowing function, compared to the current standard treatment of chemoradiotherapy.
Ethics approval
West Midlands - Solihull, 27/11/2014, ref: 14/WM/1170
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Oropharyngeal cancer
Intervention
1. Arm 1: Control arm, concomitant chemoradiotherapy, 3-weekly cisplatin 100mg/m2 or weekly 40mg/m2 with Intensity Modulated Radiotherapy (IMRT) using 70Gy in 35F +/- neck dissection as indicated by clinical and radiological assessment 3-months post treatment. This is the international gold standard.
2. Arm 2: Induction chemotherapy (3 cycles at 3-weekly intervals: Docetaxel 75mg/m2 + Cisplatin 80mg/m2 + 5-Fluorouracil (5-FU) 800mg/m2/day, daily for 4 days), followed by Arm 1.
3. Arm 3: Dose-escalated chemoradiotherapy using intensity modulated radiotherapy (IMRT) 64Gy in 25F + Cisplatin 100mg/m2 day 1 of week 1 and of week 5 or weekly 40mg/m2 (neck dissection as indicated by clinical and radiological assessment at 3-months post-treatment).
4. Arm 4: Resection of primary + selective neck dissection followed by chemoradiotherapy. For T1 & T2 primary tumour, resection must be transoral. For T3 & T4 primary tumour, resection preferably transoral if possible otherwise by open surgery.
Follow Up Length: 24 month(s); Study Entry : Registration and One or More Randomisations
Intervention type
Drug
Phase
Phase III
Drug names
Primary outcome measure
1. Definitive (efficacy) endpoint: Overall Survival (OS) - Interval in whole days between the date of randomisation and the date of death from any cause
2. Interim outcome measure (activity stages): Disease Free Survival (DFS) - Interval between the date of randomisation and the date of death or the 1st documented relapse
Secondary outcome measures
1. Total number of acute (<3 months post-treatment) and late (up to 2 years) severe (grade 3-5) toxicity events at 2 years post randomisation, measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
2. Overall and head and neck specific QoL at 2 years post randomisation, using the European Organisation for Research and Treatment of Cancer (EORTC) C30 and H&N35 Questionnaires
3. Swallowing outcomes using M.D. Anderson Dysphagia Inventory (MDADI) Questionnaire at 24 months and percutaneous endoscopic gastrostomy (PEG) utilisation rates at 1 year
4. Cost effectiveness using EuroQol Group (EQ-5D), patient diaries and primary and secondary resource utilisation data
5. Surgical complication rates in each arm
Overall trial start date
01/05/2015
Overall trial end date
01/11/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Oropharyngeal squamous cell carcinoma in base of tongue and tonsil with an Multidisciplinary Team recommendation for treatment with definitive concurrent chemoradiotherapy
2. Intermediate risk [HPV +ve OPC with N2b+ disease and greater than 10 pack year history of smoking] or high risk (HPV–ve OPC) as per Ang classification
3. Minimum life expectancy of 3 months
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
5. Adequate renal function, glomerular filtration rate >50mL/min calculated using CockcroftGault formula
6. Adequate bone marrow function (absolute neutrophil count ≥1.5 x 109/L and platelets ≥100 x 109/L)
7. Adequate liver function i.e. plasma bilirubin ≤1.5 times the upper limit of normal, and alanine aminotransferase and Alkaline phosphatase ≤2.5 x upper limit of normal
8. Prothrombin time ≤1.5 x upper limit of normal or International Normalised Ratio ≤1. 5
9. Magnesium ≥ lower limit of normal
10. No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intraepithelial neoplasia
11. Age 16-70
12. Written informed consent given
13. Surgically resectable disease if being randomised to all 4 arms
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 650; UK Sample Size: 650; Description: Patients with intermediate and high risk oropharyngeal cancer (OPC).
Participant exclusion criteria
1. Low risk OPSCC defined as:
1.1. HPV+ OPC nonsmokers or
1.2. HPV+ OPC smokers <10 pack years or
1.3. HPV+ OPC smokers >10 pack years with N02A nodal disease
2. Unfit for surgery or chemoradiotherapy regimens
3. Creatinine Clearance <50ml/min
4. Treatment with any of the following, prior to first dose of trial treatment:
4.1. Taxanes
4.2. Any Investigational Medicinal Products (IMP) within 30 days
4.3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks
4.4. Major surgery within 4 weeks
4.5. Radiotherapy:
4.5.1. With a wide field of radiation or involving >30% of total bone marrow volume, within 4 weeks
4.5.2. With a limited field of radiation, for palliation, within 2 weeks
5. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia) at the time of registration
6. History of allergic reactions to any of the IMPs used in this trial
7. Women who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of trial treatment
8. Men or women who are not prepared to practise methods of contraception of proven efficacy during treatment and for 6 months following the end of treatment
9. Pre-existing tinnitus or hearing impairment ischaemic heart disease, cerebrovascular disease, peripheral vascular disease or previous arterial embolic event
Recruitment start date
01/05/2015
Recruitment end date
01/11/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor information
Organisation
University of Birmingham
Sponsor details
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Results of this trial will be submitted for publication in a peer-reviewed journal.
Updated 08/08/2019:
Planned publication in a high-impact peer reviewed journal (approx. January 2025)
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
01/01/2025
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list