Condition category
Cancer
Date applied
29/04/2015
Date assigned
29/04/2015
Last edited
12/08/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Joshua Savage

ORCID ID

http://orcid.org/0000-0003-0599-0245

Contact details

School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2014-003389-26

ClinicalTrials.gov number

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 Trial

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

Topic: Cancer; Subtopic: Head and Neck Cancer; Disease: Head and Neck

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 measures

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

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

http://www.birmingham.ac.uk/

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

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Results of this trial will be submitted for publication in a peer reviewed journal.

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes