CISPLATIN for HPV-positive oropharyngeal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Histologically confirmed or suspected squamous cell carcinoma of the oropharynx.\n- Group B : Fit to undergo radiotherapy.\n- Group B : HPV positive by both P16 and either High Risk HPV In-Situ Hybridization (ISH) or validated Polymerase Chain Reaction (PCR) technique\n- Group C : Fit for, and able to potentially benefit from chemoRT, as decided by an MDT.\n- Group C : Willing to be treated with chemotherapy\n- Group C : HPV positive by both P16 and either High Risk HPV In-Situ Hybridization (ISH) or validated Polymerase Chain Reaction (PCR) technique\n- Group C : Bone marrow reserve adequate for chemotherapy (i.e. absolute neutrophil count (ANC) ≥ 1.5 x 109/l and platelet count ≥ 100 x 109/l).\n- Group C : Adequate GFR for Cisplatin chemotherapy, defined as GFR ≥ 50 ml/min.\n- UICC/AJCC TNM 7th edition stage T1-T3*, N0-N2b (or UICC TNM 8th edition stage T1-T3, N0-N1) disease.\n- Multidisciplinary team (MDT) decision to treat with primary transoral resection and neck dissection.\n- Patients considered fit for surgery and adjuvant radiotherapy\n- Aged 18 or over.\n- Written informed consent provided (not applicable for France).\n- Patients must be affiliated to a Social Security System (applicable for France only)\n- Patient must have signed informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent (applicable for France only).\n- Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures (applicable for France only)."}

Exclusion criteria

• {"criterion_text":"- Known HPV negative squamous cell carcinomas of the head and neck: A negative result for p16 Immunohistochemistry automatically excludes a patient from the trial. If initial p16 testing is positive but High-Risk HPV (HR HPV) In-Situ Hybridization (ISH) / Polymerase Chain Reaction (PCR) does not demonstrate the presence of HR HPV DNA, the patient will also be excluded. Patients who are p16 positive may complete swallowing assessments, excluding videofluoroscopy, and surgery whilst HR HPV DNA status is being determined (with recourse to central concordance testing, if appropriate, for UK centres). HPV positivity, as determined by p16 and the demonstration of HR HPV DNA is essential before patients undergo videofluoroscopy or randomisation.\n- Persons deprived of their liberty or under protective custody or guardianship (applicable for France only)\n- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons (applicable for France only).\n- Group B : pN2c or pN3 as per UICC/AJCC TNM 7th edition.\n- Group C : Myelosuppression\n- Group C : Pre-existing renal impairment (GFR < 50ml/min).\n- Group C : History of significant cardiac conditions, arteriopathy, or other medical conditions that preclude the use of Cisplatin and IV hydration.\n- Group C : Clinically significant hearing impairment sufficient to affect daily living (as reported by the patient) and/or pre-existing tinnitus.\n- Group C : Pre-existing peripheral neuropathy which precludes the use of Cisplatin.\n- Group C : Hypersensitivity to the active substance or other platinum compounds or to any of the excipients listed in the SPC.\n- Group C : Dehydrated condition (pre- and post-hydration is required to prevent serious renal dysfunction).\n- T4 and/or T1-T3 tumours where transoral surgery is considered not feasible.\n- Group C : pN2c or pN3 as per UICC/AJCC TNM 7th edition.\n- UICC/AJCC TNM 7th edition N2c-N3 nodal disease (or UICC/AJCC TNM 8th edition N2-N3 nodal disease).\n- Patients for whom transoral surgery and neck dissection is not considered the primary treatment modality.\n- Current smokers with clinically staged N2b disease (including smokers up to 6 months before diagnosis), even if HPV-positive. Vaping is permitted and should be considered as non-smoking status.\n- Any pre-existing medical condition likely to impair swallowing function and/ or a history of pre-existing swallowing dysfunction prior to index oropharyngeal cancer.\n- Patients with distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g., CT thorax and upper abdomen or PET-CT.\n- Patients with a history of malignancy in the last 5 years, except basal cell carcinoma of the skin or carcinoma in-situ of the cervix.\n- Women who are pregnant or breastfeeding and fertile women who will not be using contraception during the trial."}

Primary endpoints

• {"endpoint_text":"- Overall survival and swallowing function as measured by the MD Anderson Dysphagia Inventory (MDADI) score.","definition_or_measurement_approach":"Swallowing function measured by the MD Anderson Dysphagia Inventory (MDADI) score; overall survival measured as time to death (as stated: \"Overall survival and swallowing function as measured by the MD Anderson Dysphagia Inventory (MDADI) score.\")."}

Secondary endpoints

• {"endpoint_text":"- Swallowing panel measurements including qualitative and quantitative swallowing assessments as described previously.","definition_or_measurement_approach":"Panel of qualitative and quantitative swallowing assessments as described in the protocol procedures (no additional measurement detail provided in the available JSON)."}
• {"endpoint_text":"- QOL (using EORTC QLQ C30 and HN35 questionnaires).","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-C30 and QLQ-H&N35 instruments."}
• {"endpoint_text":"- Acute and late toxicity, assessed using NCI CTCAE criteria version 4.03","definition_or_measurement_approach":"Toxicity graded using NCI CTCAE v4.03 criteria."}
• {"endpoint_text":"- Overall survival, disease free survival, locoregional control, distant metastases.","definition_or_measurement_approach":"Standard clinical endpoints: overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant metastasis (DM) as described in the protocol."}

France

Earliest CTIS Part Ii Submission Date

05-11-2024

Latest Decision Or Authorization Date

16-01-2025

Processing Time Days

72

Number Of Sites

18

Number Of Participants

150

Germany

Earliest CTIS Part Ii Submission Date

19-07-2024

Latest Decision Or Authorization Date

17-01-2025

Processing Time Days

182

Number Of Sites

7

Number Of Participants

90

Primary sponsor

Full Name

Cardiff University

Organisation Type

Educational Institution

Country Of Registered Address

United Kingdom