High risk Human Papilloma Virus (HPV)-driven oropharynx cancer patients
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATIN
Current Sponsor code: Cisplatine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
C
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years old 2. Histologically confirmed HPV-positive OPSCC amenable to curative treatment with RT-CT. (HPV status is defined on the basis of the combination of 2 assays: p16 protein overexpression assessed by immunohistochemistry (IHC) and high-risk HPV DNA identification by in-situ Hybridization (ISH) orPCR. An HPV-driven OPSCC is defined as a tumor that is positive for both p16 IHC and HPV-DNA ISH or PCR) 3. According to the 8th TNM edition, eligible stages are as follow: - Irrespective of tobacco consumption: Stage T4 (any N), N2 or N3 (any T) - Only if tobacco consumption = 10 pack- years: T1-3N1 and T3N0 (T1N0 and T2N0 irrespective of tobacco consumption are not eligible for the study) 4. Planned date of chemoradiation allowing 2 Nivolumab infusions, 2 weeks apart. 5. ECOG performance status =1 6 Adequate cardiac, haematological, hepatic and renal function allowing treatment with cisplatin and nivolumab 7. Potentially reproductive patients must agree to use a highly effective contraceptive method while on treatment and up to 6 months after the end of chemoradiation. 8. Women of childbearing potential must have a negative serum or urine pregnancy test done within 72 hours before randomisation. 9. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures (including mandatory study-specific biopsies) 10. Subjects must have at least one lesion amenable to biopsy. 11. Consent to provide archived tumor tissue sample, if available. 12. Patients must be affiliated to a Social Security System. 13. Patient information and written informed consent form signed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 41 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Prior treatment for OPSCC 2. Prior treatment with anti-PD-1/PD-L1 and CTLA-4 3. Distant metastases 4. Tumor embolization within 28 days prior to the randomisation 5. Contra-indication to receive high-dose cisplatin 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness and social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent. 7. Current or prior use of immunosuppressive medication within 14 days before randomisation, including intranasal and inhaled corticosteroids or systemic corticosteroids. 8. Active or prior documented autoimmune or inflammatory disease within the 2 years prior to randomisation (including inflammatory bowel disease [e.g., ulcerative colitis, Crohn’s disease], celiac disease, irritable bowel disease, or other serious chronic gastrointestinal conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis; hypophysitis, uveitis, etc.) The following are exceptions to these criteria:a) Subjects with vitiligo or alopecia, b) Subjects with hypothyroidism (e.g.,Hashimoto syndrome) stable on hormone replacement and c) Subjects with psoriasis not requiring systemic treatment (within the past 2 years). 9. History of primary immunodeficiency or organ transplant requiring immunosuppressive drugs 10. Patients with a known HIV, active hepatitis B or C infection. 11. Other invasive malignancy within 3 years of randomisation except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured. 12. Pregnant women or women who are breast-feeding. 13. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the study. 14. Individuals deprived of liberty or placed under the authority of a tutor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the feasibility and tolerance of neoadjuvant nivolumab treatment before chemoradiation (RT-CT) in “high risk” HPV-driven Oropharyngeal squamous cell carcinomas (OPSCC).;Secondary Objective: - To assess safety with acute and late toxicities (according to NCI CTC-AE v5.0) - To assess the efficacy with Objective Response Rate (ORR) after nivolumab infusion and after completion of chemoradiation by CT-scan and MRI according to RECIST 1.1 and PET-scan. - To assess the efficacy with Overall Survival (OS), Locoregional control (LRC) and Progression-Free Survival (PFS) - To evaluate potential predictive biomarkers of clinical response secondary to nivolumab infusions.;Primary end point(s): The rate of patients : (1) who can receive the 2 nivolumab infusions planned at D1 and between D14 to D16 among patients in the experimental arm And (2) who can receive chemoradiation at D30 (-2 /+7) after the second nivolumab infusion, without delay of more than 7 days with respect to the planned start of chemoradiation (RT-CT) (i.e., with RT-CT starting at the latest on D37) among patients in the experimental arm And (3) with no radiotherapy break of one week or more, among patients in the experimental arm and patients in the control arm separately And (4) with minimal dose of radiotherapy (dose received >95% of theoretical dose) among patients in the experimental arm and patients in the control arm separately And (5) with minimal dose of chemotherapy of = 200 mg/m2 of cisplatin (CDDP) among patients in the experimental arm and patients in the control arm separately In the experimental arm, a success is defined by the achievement of the 5 criteria. In the control arm, a success is defined by the achievement of the three criteria number (3), (4), and (5).;Timepoint(s) of evaluation of this end point: _ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Acute toxicity assessed according to NCI CTC-AE v5.0 during and after nivolumab treatment and RT-CT - Delayed toxicity assessed according to NCI CTC-AE v5.0 - Objective Response Rate between baseline and 12 to 17 days after the 2nd infusion of nivolumab (for patients receiving nivolumab). Radiological response will be assessed by CT-scan and MRI according to RECIST 1.1. SUV (standardized uptake value) evolution will be assessed by PET-scan. These examinations will be scheduled at patient’s inclusion. - Tumor response between baseline and 3 months after the end of RT-CT for all patients. Radiological response will be assessed by CT-scan and MRI according to RECIST 1.1. SUV evolution will be assessed by PET-scan. - Overall Survival (OS), defined as the time from randomization to death from any cause. Patients still alive at the time of analysis will be censored at the last known alive date. - Locoregional control (LRC), defined as the absence of disease progression or recurrence at the site of the primary tumor and loco-regional lymph nodes. - Progression-Free Survival (PFS), defined as the time from randomization to progression or death from any cause. Patients still alive at the time of analysis without documented progression will be censored at last known alive date.;Timepoint(s) of evaluation of this end point: _ | — |
Countries
France
Contacts
Public ContactProject Manager
UNICANCER
Outcome results
None listed