Oropharyngeal cancer Cancer Malignant neoplasm of oropharynx
Conditions
Interventions
Current intervention as of 29/10/2021:
1. Arm 1: Control arm, concomitant chemoradiotherapy, 3-weekly cisplatin 100mg/m2 or weekly 40mg/m2 with Intensity Modulated Radiotherapy (IMRT) using 70Gy in 3
Study Entry : Registration and One or More Randomisations
(updated 12/12/2022: Arms 2, 3, 4 are now closed to recruitment).
_____
Previous intervention:
1. Arm 1: Control arm, concomitant chemorad
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 28/02/2022: 1. Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil (includes bilateral tumours) and uvula, with an Multidisciplinary Team (MDT) recommendation for treatment with definitive concurrent chemoradiotherapy. 2. All OPC T4 or N3 (HPV-pos and HPV-neg) OR All HPV–neg OPC T1-T4, N1-N3 or T3-4, N0 OR HPV-pos) OPC T1-T4 with N2b-N3, 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 (APPENDIX 3) 5. Body weight >30kg 6. Adequate renal function, estimated glomerular filtration rate (eGFR) >50mL/min calculated using Cockcroft-Gault formula (APPENDIX 4)* 7. Adequate bone marrow function (absolute neutrophil count (ANC) =1.5 x 109/L, haemoglobin =9.0g/dL and platelets =100 x 109/L) 8. Adequate liver function i.e. serum bilirubin =1.5 times the upper limit of normal (ULN) ,AST (SGOT)/ ALT(SGPT) =2.5 x institutional upper limit of normal 9. Prothrombin time (PT) =1.5 x ULN or International Normalised Ratio (INR) =1. 5 10. No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intra-epithelial neoplasia (CIN) 11. Age 18-70 12. Written informed consent given for the trial 13. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female premenopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women - Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiationinduced menopause with last menses >12 months ago, had chemotherapy-induced menopause with last menses >12 months ago or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 14. Willingness to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up Previous 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
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 28/02/2022: 1. All T1-T2,N0 OPC (HPV-pos or HPV-neg) 2. HPV positive patients who are: • T1-T3, N0-N2c non-smokers • T1-T3, N0-N2c smokers with =10 pack years or • T1-T3, N0-N2a smokers with =10 pack years 3. Unfit for chemoradiotherapy regimens 4. Creatinine Clearance 5. Treatment with any of the following, prior to randomisation: a. Any Investigational Medicinal Products (IMP) within 30 days b. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks c. Major surgical procedure (as defined by the Investigator) within 4 weeks, unless for diagnostic urposes d. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy is acceptable) 6. History of allergic reactions or hypersensitivity 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, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, including any patient known to have psychiatric illness/social situations that would limit compliance with study requirements, substantially increase the risk of incurring AEs or compromise the ability of the patient to give written informed consent 8. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 9. 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 10. 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 11. Any condition that, in the opinion of the Investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results 12. Any previous treatment with a PD-L or PD-L1 inhibitor, including durvalumab 13. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection) • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent • Steroids as premedication for hypersensitivity reactions (e.g, CT scan, premedication). 14. 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), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
England, United Kingdom
Outcome results
None listed