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CompARE

Phase III randomised controlled trial Comparing Alternative Regimens for Escalating treatment of intermediate and high-risk oropharyngeal cancer

 

Acronym: 
CompARE

Summary and Eligibility: 
The CompARE study has been set up to investigate which treatment is most effective for patients who have higher-risk oropharyngeal cancer. The purpose of this study is to consider using additional treatments in conjunction with standard chemoradiotherapy to increase cure rates of higher-risk oropharyngeal cancer. This will  be done  by  adding  surgery  or  more  chemotherapy or higher  dose radiotherapy  to  the  standard chemoradiotherapy

Inclusion Criteria: 
Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil with an 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, N1-3 or T3-T3, N0

OR

HPV +ve (positive) OPC T1-4 with N2b-N3 nodes AND who are smokers ≥10 pack year current or previous smoking history

Minimum life expectancy of 3 months

Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix 2)

Adequate renal function, glomerular filtration rate (GFR) >50mL/min calculated using Cockcroft-Gault formula (Appendix 3)*

Adequate bone marrow function (absolute neutrophil count (ANC) ≥1.5 x 109/L 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)

Age 18-70

Written informed consent given for the trial

Surgically resectable disease if being randomised to all 4 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

Exclusion Criteria:

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 chemotherapy 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 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 or 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

Additional Exclusion Criteria for Arm 5 Only:
Any previous treatment with a PD-L or PD-L1 inhibitor, including durvalumab

Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone,or an equivalent corticosteroid dose

Active or prior documented autoimmune or inflammatory disorders

including inflammatory bowel disease e.g. colitis or Crohn's disease, diverticulitis (with the exception of diverticulosis), celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis).
The following are exceptions to this criterion:

Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g. following Hashimoto syndrome
Stable on hormone replacement
Any chronic skin condition that does not require systemic therapy

Patients without active disease in the last 5 years may be included
but only after consultation with the study physician

Patients with an active non-infective pneumonitis

History of primary immunodeficiency

History of allogeneic organ transplant

Status: 
Open

Lead Centre: 
Queen Elizabeth Hospital, Birmingham

Discussions with patients will be audio recorded as part of the QRI
Differential randomisation: centres can choose to randomise patients to all 4 treatment arms or to the three non-surgical arms or if patient refuses surgical arm
Samples collected for translational research (CompARE Collect) if the patient has consented. Compare Collect ICF should be completed

Study Coordinator: 

Dr Charlotte Firth
CompARE Trial Coordinator
Cancer Research UK Clinical Trials Unit (CRCTU)

Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston

Birmingham B15 2TT

CRCU logo

Tel:      +44 (0)121 414 5101
Fax:     +44 (0)121 414 8392

CRCTU Website  Email:  [email protected] 



 

 

 

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