CISPLATIN for Oropharyngeal squamous cell carcinoma | Oropharyngeal cancer

Inclusion criteria

• {"criterion_text":"- 1. Oropharyngeal squamous cell carcinoma (OPSCC) in base of tongue and tonsil (includes bilateral tumours) and uvula, with a Multidisciplinary Team (MDT) recommendation for treatment with definitive concurrent chemoradiotherapy.\n- 10. No cancers in previous 5 years, except basal cell carcinoma of skin and cervical intra-epithelial neoplasia (CIN)\n- 11. Aged 18-70\n- 12. Written informed consent given for the trial\n- 13. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following agespecific requirements apply: - Women <50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and folliclestimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). - Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced 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).\n- 14. Willingness to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations including follow up.\n- 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 nodes AND who are smokers ≥ 10 pack years current or previous smoking history\n- 3. Minimum life expectancy of 3 months\n- 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n- 5. Body weight of >30kg\n- 6. Adequate renal function, estimated glomerular filtration rate (eGFR) >50ml/min calculated using Cockcroft-Gault formula\n- 7. Adequate bone marrow function (absolute neutrophil count (ANC) ≥1.5 x 10^9/L, haemoglobin ≥9.0g/dL and platelets ≥100 x 10^9/L)\n- 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\n- 9. Prothrombin time (PT) ≤1.5 x ULN or International Normalised Ratio (INR) ≤1. 5"}

Exclusion criteria

• {"criterion_text":"- 1. All T1-T2,N0 OPC (HPV-pos or HPV-neg)\n- 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\n- 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\n- 12. Republic of Ireland only – Treatment with live vaccines, including yellow fever vaccine.\n- 13. Any previous treatment with PD-L or PD-L1 inhibitor, including durvalumab\n- 14. 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)\n- 15. 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 (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 celiac disease controlled by diet alone\n- 16. History of active primary immunodeficiency\n- 17. History of allogeneic organ transplant\n- 18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab. Inactivated viruses, such as those in the influenza vaccine, are permitted\n- 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\n- 3. Unfit for chemoradiotherapy regimens\n- 4. Creatinine Clearance <50ml/min\n- 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 purposes. d. Concurrent use of hormonal therapy for non-cancerrelated conditions (e.g., hormone replacement therapy is acceptable)\n- 6. History of allergic reactions or hypersensitivity to any of the IMPs and excipients used in this trial\n- 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 or any subject known to have psychiatric illness/social situations that would limit compliance with study requirement, substantially increase the risk of incurring AEs or compromise the ability of the subject to give written informed consent\n- 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\n- 9. Women who are pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to randomisation"}

Primary endpoints

• {"endpoint_text":"- 1. Definitive (efficacy) endpoint: Overall Survival (OS) time","definition_or_measurement_approach":""}
• {"endpoint_text":"- 2. Interim outcome measure (activity stages): Event Free Survival (EFS) time","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- 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 and version 3.0 for scoring mucositis. Radiation Therapy Oncology Group (RTOG) Radiation Morbidity Scoring Criteria will be used to grade late side effects due to radiotherapy","definition_or_measurement_approach":"Measured by CTCAE v4.0 and v3.0 for scoring mucositis; RTOG Radiation Morbidity Scoring Criteria for late radiotherapy side effects; assessed at 2 years post randomisation"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured using EORTC C30 and H&N35 questionnaires at 2 years post randomisation"}
• {"endpoint_text":"- 3. Swallowing outcomes using M.D. Anderson Dysphagia Inventory (MDADI) Questionnaire at 24 months and percutaneous endoscopic gastrostomy (PEG) utilisation rates at 1 year","definition_or_measurement_approach":"Swallowing measured by MDADI at 24 months; PEG utilisation rates measured at 1 year"}
• {"endpoint_text":"- 4. Cost effectiveness using EuroQol Group (EQ-5D) and primary and secondary resource utilisation data","definition_or_measurement_approach":"Cost-effectiveness assessed using EQ-5D and resource utilisation data"}
• {"endpoint_text":"- 5. Surgical complication rates in each arm","definition_or_measurement_approach":""}
• {"endpoint_text":"- 6. Translation Research Outcome Measures: 1. To determine tumour phenotype correlation with treatment response by molecular analyses","definition_or_measurement_approach":""}
• {"endpoint_text":"- 7. Translational Research Outcome Measures: 2. To develop validation of a patient stratification classifier using markers of proliferation, p53 and related pathways, apoptotic markers, hypoxia and DNA damage response and other genomic and mRNA and circulating DNA markers","definition_or_measurement_approach":""}
• {"endpoint_text":"- 8. Translational Research Outcome Measures: 3. To correlate OS and EFS with Programmed cell death ligand 1 (PD-L1) expression and treatment with durvalumab","definition_or_measurement_approach":""}

Ireland

Earliest CTIS Part Ii Submission Date

28-08-2024

Latest Decision Or Authorization Date

29-10-2024

Processing Time Days

62

Number Of Sites

4

Number Of Participants

24

Primary sponsor

Full Name

The University Of Birmingham

Organisation Type

Educational Institution

Country Of Registered Address

United Kingdom

Third parties

• {"country":"United Kingdom","full_name":"Newcastle University","duties_or_roles":"HPV testing to confirm eligibility","organisation_type":"Educational Institution"}
• {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"Packaging, labelling and certification of durvalumab. Shipment of durvalumab to hospital sites.","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"University Of Bristol","duties_or_roles":"Qualitative Recruitment Investigation","organisation_type":"Educational Institution"}
• {"country":"United Kingdom","full_name":"University Hospitals Birmingham NHS Foundation Trust","duties_or_roles":"PD-L1 testing","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Packaging, labelling and certification of durvalumab. Shipment of durvalumab to hospital sites.","organisation_type":"Pharmaceutical company"}