TRETINOIN for Oropharyngeal squamous cell carcinoma|Laryngeal squamous cell carcinoma|Hypopharyngeal squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- I1. Male or female patients aged ≥ 18 years old at time of inform consent signature"}
• {"criterion_text":"- I9\tFertile men must agree to use an effective method of contraception during the study and for up to 1 month after the end of study treatments."}
• {"criterion_text":"- I11. Patients must be covered by a medical insurance in country where applicable."}
• {"criterion_text":"- I10. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed and should be able and willing to comply with study visits and procedures as per protocol."}
• {"criterion_text":"- I2. Patients with primary head and neck tumour up to, but not crossing the midline, previously untreated with histologically-confirmed squamous cell carcinoma of: 1) the oropharynx p16-, larynx or hypopharynx : T1/N2a-N2b, T2/N0-N2b, T3/N0-N2b (UICC 8th Ed.), or 2) the oropharynx p16+ : T1/N1 (multiple nodes), T2-T3/N0-N1 (UICC 8th Ed.)"}
• {"criterion_text":"- I3. Patients with lymph node staging assessed by a FDG-PET/CT with no contralateral nodal uptake"}
• {"criterion_text":"- I4. Patients amenable to treatment with RT or concomitant chemo-radiotherapy.as decided by the treating physician as a function of tumor stage, tumor location, performance of the patients"}
• {"criterion_text":"- I5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1"}
• {"criterion_text":"- I6. Adequate hematologic and end-organ function, defined by the following laboratory test results obtained within 7 days prior to randomisation : 1) Hematological (without transfusion within 2 weeks) - Neutrophils count > 1,5x10.9 /L - Platelets count > 75x10.9/L - WBC≥ 3.0x10.9/L 2) Hepatic function - o\tTotal Bilirubin < 1.5 × ULN (except for Gilbert's syndrome which will allow bilirubin ≤ 3 ULN), - Alanine aminotransferase (ALT) ≤ 2.5×ULN - Aspartate aminotransferase (AST) ≤ 2.5×ULN - Albumin >3.0g/dL 3) Renal function - Serum creatinine < 1.5xULN"}
• {"criterion_text":"- I7. QTcF ≤450ms for men and 470ms for women, from 3 electrocardiograms on screening ECG, within 7 days prior randomisation"}
• {"criterion_text":"- I8. Women patients of child-bearing potential are eligible, provided they have a negative serum or urine pregnancy test within 7 days prior randomisation, and agrees to use adequate contraception for up to 1 month after the end of study treatments."}

Exclusion criteria

• {"criterion_text":"- E1. Patient with primary tumor crossing the midline or patients with bilateral primary tumors."}
• {"criterion_text":"- E10. Patient with infectious diseases: - severe infection within 4 weeks prior to randomisation, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, - active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening), - active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at screening, - HIV infection, - active tuberculosis."}
• {"criterion_text":"- E11. Patient with any psychological, cognitive, familial, sociological or geographical condition potentially hampering compliance with the study protocol, completion of patient reported measures and follow-up schedule; those conditions should be discussed with the patient before registration in the trial."}
• {"criterion_text":"- E12. Patient with known hypersensitivity to tretinoin, other retinoids, soya, peanut or to any of the excipients of vesanoid listed in section 6.3."}
• {"criterion_text":"- E13. Patient with known malabsorption syndrome and/or unable to swallow oral medication."}
• {"criterion_text":"- E14. Patient with ongoing or expected need for concomitant treatment with vitamin A, tetracyclines, other retinoids, anti-fibrinolytic agent, and strong inducers or inhibitors of CYP3A4."}
• {"criterion_text":"- E15. Pregnant or lactating woman."}
• {"criterion_text":"- E2. Patients with T1-N0 (p16-), T1-N1 (p16-), T1-N0 (p16+), T4 (p16- and p16+), bilateral lymph nodes or nodal disease more than 6 cm (p16- and p16+)."}
• {"criterion_text":"- E3. Patients with unknown primary tumor size as per TNM i.e. T0-N1 to T0-N3, p16- or p16+."}
• {"criterion_text":"- E4. Patients with contralateral FDG-PET/CT nodal uptake."}
• {"criterion_text":"- E5. Patient with any previous anti-cancer therapy for HNSCC (all prior treatments are forbidden: chemotherapy, radiotherapy, targeted therapy, immunotherapy or any other therapy approved or experimental)."}
• {"criterion_text":"- E6. Patient with malignancies other than HNSCC within 3 years prior to randomisation with the exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer treated surgically with curative intent."}
• {"criterion_text":"- E7. Patient with ongoing or anticipation of need for systemic immunosuppressive medication (including, but not limited to, glucocorticoids, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents); with the exceptions of intranasal, inhaled or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid."}
• {"criterion_text":"- E8. Patient with ongoing or anticipation of need for systemic immunostimulatory agents (including, but not limited to, interferons and IL-2)."}
• {"criterion_text":"- E9. Patient with concurrent treatment with any other anti-cancer treatment, approved or investigational agent or participation in another clinical trial with therapeutic intent."}

Primary endpoints

• {"endpoint_text":"- Event Free Survival (EFS)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Local relapse free survival; Regional relapse free survival; Metastases free survival; Rate of pathologically positive lymph nodes at neck node dissection performed at 4 months after the completion of (chemo)-radiotherapy for those patients benefiting from a neck node dissection; EFS considering that pathologically positive lymph nodes at neck node dissection performed at 4 months after the completion of (chemo)-radiotherapy is not an event and Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of AEs using NCI CTCAE 5.0","definition_or_measurement_approach":""}
• {"endpoint_text":"- Changes from baseline in i) Global Health Scale/Quality of Life and Fatigue using European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and EQ5D and ii) swallowing and Pain using EORTC QLQ-H&N43 questionnaire","definition_or_measurement_approach":""}
• {"endpoint_text":"- * Cost-effectiveness (based on efficacy) * Analysis and Cost-Utility (based on QALY) Analysis","definition_or_measurement_approach":""}
• {"endpoint_text":"- Exploratory objetives: Immunomonitoring on isolated PBMCs","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

06-08-2024

Latest Decision Or Authorization Date

21-10-2024

Processing Time Days

76

Number Of Sites

12

Number Of Participants

400

Belgium

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

23-10-2024

Processing Time Days

29

Number Of Sites

1

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

25-10-2024

Processing Time Days

22

Number Of Sites

4

Number Of Participants

30

Primary sponsor

Full Name

Centre Leon Berard

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France