Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma

Prior treatment

• E5. Patient with any previous anti-cancer therapy for HNSCC (all prior treatment are forbidden: chemotherapy, radiotherapy, targeted therapy, immunotherapy or any other therapy approved or experimental).
• 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.
• 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.
• E9. Patient with concurrent treatment with any other anti-cancer treatment, approved or investigational agent or participation in another clinical trial with therapeutic intent.
• Severe infection within 4 weeks prior to randomisation, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia,
• Active tuberculosis.
  • 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.
  • E12. Patient with known hypersensitivity to tretinoin, other retinoids, soya, peanut or to any of the excipients of vesanoid.
  • E13. Patient with known malabsorption syndrome and/or unable to swallow oral medication.
  • 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.
  • E15.Pregnant or lactating woman.

Other illness

• 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+).
• E10. Patient with infectious diseases :
• 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,

Other

• E1. Patient with primary tumor crossing the midline or patients with bilateral primary tumors.
• E3. Patients with unknown primary tumor size as per TNM i.e. T0-N1 to T0-N3, p16- or p16+.
• E4. Patients with contralateral FDG-PET/CT nodal uptake.
• E8. Patient with ongoing or anticipation of need for systemic immunostimulatory agents (including, but not limited to, interferons and IL-2).

• I1. Male or female patients aged ≥ 18 years old at time of inform consent signature.
• I2. Patients with primary head and neck tumour up to, but not crossing the midline, previously untreated with histologically-confirmed squamous cell carcinoma of:
• the oropharynx p16-, larynx or hypopharynx : T1/N2a-N2b, T2/N0-N2b, T3/N0-N2b (UICC 8th Ed.), or
• the oropharynx p16+ : T1/N1 (multiple nodes), T2-T3/N0-N1 (UICC 8th Ed.).
  • I3. Patients with lymph node staging assessed by an FDG-PET/CT with no contralateral nodal uptake.
  • 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.
  • I5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
  • I6. Adequate hematologic and end-organ function, defined by the following laboratory test results obtained within 7 days prior to randomisation :
  • Hematological (without transfusion within 2 weeks) :
• Neutrophils count \> 1.5 × 109 /L
• Platelets count \> 75 × 109 /L
• WBC≥ 3.0 × 109 /L
  • Hepatic function :
• Total 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
  • Renal function :
• Serum creatinine \< 1.5 ×ULN.
  • I7. QTcF ≤450ms for men and 470ms for women, from 3 electrocardiograms on screening ECG, within 7 days prior randomisation.
  • 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.
  • I9. Fertile 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.
  • 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.
  • I11. Patients must be covered by a medical insurance in country where applicable.