CompARE: Escalating Treatment of Intermediate and High-risk Oropharyngeal Cancer (OPC)

NCT04116047 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: RG 14-0932014-003389-26ISRCTN41478539
• Study Type: interventional
• Target: 785
• Locations: 2 countries
• Sites: 38

Brief Summary

CompARE is a multicentre, phase III open-label randomised controlled trial using an adaptive, Multi-Arm, Multi-Stage (MAMS) design.

Conditions

Oropharyngeal Cancer

Keywords

Oropharyngeal cancer; HPV

Outcome Measures

Primary Outcomes (2)

• Patient Overall survival (OS)

  defined as the interval in whole days between date of randomisation and date of death from any cause

  from randomisation until date of death from any cause (follow-up until 8 years post-treatment)

• Patient Event Free Survival (EFS)

  defined as the interval in whole days between date of randomisation until date of progression/persistence/recurrence/death

  From randomisation until date of progression/persistence/recurrence/death (follow-up until 8 years post-treatment)

Secondary Outcomes (9)

• Number of Acute (<3 months post-treatment) toxicity events experienced

  From date of randomisation until 2 year follow-up

• Number of late (up to 2 years post-treatment) toxicity events experienced using CTCAE

  From date of randomisation until 2 year follow-up

• Number of late (up to 2 years post-treatment) toxicity events experienced using RTOG

  From date of randomisation until 2 year follow-up

• Head and neck specific quality of life at 2 years post-randomisation using EORTC C30

  From date of randomisation until 2 year follow-up

• Head and neck specific Quality of Life at 2 years post-randomisation

  From date of randomisation until 2 year follow-up

Study Arms (2)

Arm 1 (control): chemoradiotherapy

ACTIVE COMPARATOR

Concomitant chemoradiotherapy, 3-weekly cisplatin 100mg/m2 or weekly 40mg/m2 with Intensity Modulated Radiotherapy (IMRT) using 70 gray (Gy) in 35F(fractions) +/- neck dissection as indicated by clinical and radiological assessment 3-months post treatment. This is the international gold standard.

Drug: Cisplatin; Procedure: Radiotherapy

Arm 5: Durvalumab + Arm 1

EXPERIMENTAL

One dose of induction durvalumab 1500mg by intravenous (IV) infusion followed by arm 1 within four weeks. Within one-two weeks after the completion of arm 1, durvalumab 1500mg every four weeks will be initiated for a total of 6 months

Drug: Cisplatin; Drug: Durvalumab; Procedure: Radiotherapy

Interventions

Cisplatin DRUG

Also known as: CDDP, Platinol

Arm 1 (control): chemoradiotherapy; Arm 5: Durvalumab + Arm 1

Durvalumab DRUG

Also known as: MEDI-4736, Imfinzi

Arm 5: Durvalumab + Arm 1

Radiotherapy PROCEDURE

Arm 1 (control): chemoradiotherapy; Arm 5: Durvalumab + Arm 1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil with a Multidisciplinary Team (MDT) recommendation for treatment with definitive concurrent chemoradiotherapy
• All OPC T4 or N3 (HPV+ and HPV-) OR all HPV -ve (negative) OPC T1-T4, N1-N3 or T3-4, N0 OR HPV +ve (positive) OPC T1-T4 with N2b-N3 nodes AND who are smokers ≥ 10 pack years current or previous smoking history
• Minimum life expectancy of 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate renal function, glomerular filtration rate (GFR) \>50ml/min calculated using Cockcroft-Gault formula
• Adequate bone marrow function (absolute neutrophil count (ANC) ≥1.5 x 109/L, haemoglobin ≥9.0g/dL and platelets ≥100 x 109/L)
• Adequate liver function i.e. plasma bilirubin ≤1.5 times the upper limit of normal (ULN), and alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤2.5 x ULN
• Prothrombin time (PT) ≤1.5 x ULN or International Normalised Ratio (INR) ≤1. 5
• Magnesium ≥ lower limit of normal
• No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intra-epithelial neoplasia (CIN)
• Aged 18-70
• Written informed consent given for the trial
• Surgically resectable disease if being randomised to all four arms
• Females must either be of non-reproductive potential (i.e. post-menopausal by history: ≥55 years old and no menses for ≥1 year without an alternative medical cause; or history of hysterectomy, or history of bilateral tubal ligation or history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
• Willingness to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up

You may not qualify if:

• All T1-T2,N0 OPC (HPV +ve or HPV-ve)
• HPV positive patients who are:
• T1-T3, N0-N2c non-smokers T1-T3, N0-N2c smokers with ≤10 pack years or T1-T2, N0-N2a smokers with ≥10 pack years
• Unfit for chemoradiotherapy regimens
• Creatinine Clearance \<50ml/min
• Treatment with any of the following, prior to randomisation:
• Any Investigational Medicinal Products (IMP) within 30 days
• Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks
• Major surgery within 4 weeks
• History of allergic reactions to any of the IMPs and excipients used in this trial
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Women who are pregnant or breast-feeding. Women of child- bearing potential must have a negative pregnancy test performed within 7 days prior to randomisation
• 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
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• Any previous treatment with PD-L or PD-L1 inhibitor, including durvalumab

Sponsors & Collaborators

• University of Birmingham: lead
• AstraZeneca: collaborator
• Cancer Trials Ireland: collaborator

Study Sites (38)

St Luke's Hospital

Dublin, Dublin 6, Ireland

Location

St James's Hospital

Dublin, Dublin 8, Ireland

Location

Aberdeen Royal Infirmary

Aberdeen, Aberdeen, AB25 2ZN, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, Bristol, BS2 8ED, United Kingdom

Location

Velindre Cancer Centre

Cardiff, Cardiff, CF14 2TL, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

Leicester Royal Infirmary

Leicester, East Midlands, LE1 5WW, United Kingdom

Location

Castle Hill Hospital

Cottingham, East Yorkshire, HU16 5JQ, United Kingdom

Location

Western General Hospital

Edinburgh, Edinburgh, EH4 2XU, United Kingdom

Location

Colchester General Hospital

Colchester, Essex, CO4 5JL, United Kingdom

Location

Queen's Hospital

Romford, Essex, RM7 0AG, United Kingdom

Location

Royal Preston Hospital

Preston, Lancashire, PR2 9HT, United Kingdom

Location

North Middlesex Hospital

London, London, N18 1QX, United Kingdom

Location

James Cook University Hospital

Middlesbrough, North Yorkshire, TS4 3BW, United Kingdom

Location

York Hospital

York, North Yorkshire, YO31 8HE, United Kingdom

Location

Nottingham City Hospital

Nottingham, Nottingham, NG5 1PB, United Kingdom

Location

Churchill Hospital

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Weston Park Hospital

Sheffield, South Yorkshire, S10 2SJ, United Kingdom

Location

Singleton Hospital

Swansea, Swansea, SA2 8QA, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

University Hospital Coventry

Coventry, West Midlands, CV2 2DX, United Kingdom

Location

Newcross Hospital

Wolverhampton, West Midlands, WV10 OQP, United Kingdom

Location

Bradford Royal Infirmary

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

Location

St James's University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Cheltenham General Hospital

Cheltenham, GL53 7AN, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Aintree University Hospital

Liverpool, L9 7AL, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Royal Shrewsbury Hospital

Shrewsbury, SY3 8XQ, United Kingdom

Location

Musgrove Park Hospital

Taunton, TA1 5DA, United Kingdom

Location

Torbay Hospital

Torquay, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Cisplatin; durvalumab; Radiotherapy

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Prof Mehanna

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: October 4, 2019
• Study Start: July 1, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (36); IE (2)