Oropharyngeal Cancer
Conditions
Keywords
Oropharyngeal cancer, HPV
Brief summary
CompARE is a multicentre, phase III open-label randomised controlled trial using an adaptive, Multi-Arm, Multi-Stage (MAMS) design.
Detailed description
The CompARE Trial examines alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer in an adult patient population. The aim is to assess whether escalated radiotherapy, adding surgery or immunotherapy will improve overall survival and quality of life in these patients.
Interventions
DRUGCisplatin
DRUGDurvalumab
PROCEDURERadiotherapy
Sponsors
University of Birmingham
AstraZeneca
Cancer Trials Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil with a Multidisciplinary Team (MDT) recommendation for treatment with definitive concurrent chemoradiotherapy 2. 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 3. Minimum life expectancy of 3 months 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 5. Adequate renal function, glomerular filtration rate (GFR) \>50ml/min calculated using Cockcroft-Gault formula 6. Adequate bone marrow function (absolute neutrophil count (ANC) ≥1.5 x 109/L, haemoglobin ≥9.0g/dL and platelets ≥100 x 109/L) 7. 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 8. Prothrombin time (PT) ≤1.5 x ULN or International Normalised Ratio (INR) ≤1. 5 9. Magnesium ≥ lower limit of normal 10. No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intra-epithelial neoplasia (CIN) 11. Aged 18-70 12. Written informed consent given for the trial 13. Surgically resectable disease if being randomised to all four arms 14. 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 15. 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
1. All T1-T2,N0 OPC (HPV +ve or HPV-ve) 2. 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 3. Unfit for chemoradiotherapy regimens 4. Creatinine Clearance \<50ml/min 5. Treatment with any of the following, prior to randomisation: 1. Any Investigational Medicinal Products (IMP) within 30 days 2. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks 3. Major surgery within 4 weeks 6. History of allergic reactions to any of the IMPs and excipients used in this trial 7. 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 8. 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 9. 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 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Event Free Survival (EFS) | From randomisation until date of progression/persistence/recurrence/death (follow-up until 8 years post-treatment) | defined as the interval in whole days between date of randomisation until date of progression/persistence/recurrence/death |
| Patient Overall survival (OS) | from randomisation until date of death from any cause (follow-up until 8 years post-treatment) | defined as the interval in whole days between date of randomisation and date of death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Acute (<3 months post-treatment) toxicity events experienced | From date of randomisation until 2 year follow-up | Total number of acute (\<3 months post-treatment) severe (grade 3-5) toxicity events experienced. Adverse events will be collected post-treatment and graded according to Common Terminology Criteria for Adverse Events (CTCAE). |
| Number of late (up to 2 years post-treatment) toxicity events experienced using CTCAE | From date of randomisation until 2 year follow-up | Severe (grade 3-5) adverse events will be collected up to 2 years post randomisation, these events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and version 3.0 for scoring mucositis. |
| Number of late (up to 2 years post-treatment) toxicity events experienced using RTOG | From date of randomisation until 2 year follow-up | Late and severe toxicity events at 2 years post randomisation,will be collected and graded using Radiation Therapy Oncology Group (RTOG) Radiation Morbidity Scoring Criteria |
| Head and neck specific quality of life at 2 years post-randomisation using EORTC C30 | From date of randomisation until 2 year follow-up | Patients will complete the European Organisation for Research and Treatment of Cancer (EORTC) C30 questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment |
| Head and neck specific Quality of Life at 2 years post-randomisation | From date of randomisation until 2 year follow-up | Patients will complete the European Organisation for Research and Treatment of Cancer (EORTC) H\&N35 questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment |
| Swallowing outcomes assessed using MDADI Questionnaire at 24 months post-chemoradiotherapy | From date of randomisation until 2 year follow-up | Patients will complete the M.D. Anderson Dysphagia Inventory (MDADI) Questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment |
| Cost effectiveness of treatment as assessed using EuroQol Group (EQ-5D) questionnaire | From date of randomisation until 2 year follow-up | Patients will complete the EuroQol Group (EQ-5D) questionnaire at baseline, at the end of treatment, and during the follow-up period until 2 years post-treatment |
| Levels of Percutaneous Endoscopic Gastrostomy (PEG) use | From date of randomisation until 2 year follow-up | PEG use will be assessed at baseline, throughout treatment and during 2 year follow-up period |
| Surgical complication rates in each arm for patients who require a neck dissection at 4 months following the 3 month post-chemoradiotherapy assessment scan. | At 4 months following the 3 month post-chemoradiotherapy scan | Surgical complication rates will be assessed at trial visits if a neck dissection is required at 4 months post-chemotherapy |
Countries
Ireland, United Kingdom
Contacts
PRINCIPAL_INVESTIGATORProf Mehanna
University of Birmingham
Outcome results
None listed