A Multicenter, Randomized, Open Label, Phase II Study Evaluating the Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Oropharynx Cancer
- Sponsor
- UNICANCER
- Enrollment
- 62
- Locations
- 11
- Primary Endpoint
- The rate of patients that fulfill the 3 or 5 conditions as described below (Feasibility assessment of nivolumab neoadjuvant treatment before chemoradiation)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The aim of this research is to study the feasibility of neoadjuvant treatment before chemoradiation in "high risk" HPV-driven Oropharynx cancer
Detailed Description
Methodology: Patient screened wil be randomized 2:1 between 2 arms: * Experimental arm: Nivolumab 2 infusions (2 weeks part) before standard of care chemoradiation for 7 weeks with cisplatin at week 1, 4, and 7 * Control arm: Standard of care chemoradiation for 7 weeks with cisplatin at week 1, 4, and 7 Primary Objective: To assess the feasibility and tolerance of neoadjuvant nivolumab treatment before chemoradiation in "high-risk" HPV-driven Oropharynx Cancer
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years old
- •Histologically confirmed HPV-positive Oropharyngeal squamous cell carcinoma (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) or PCR. An HPV-driven OPSCC is defined as a tumor that is positive for both p16 IHC and HPV-DNA ISH or PCR)
- •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)
- •Planned date of chemoradiation allowing 2 treatment infusions, 2 weeks apart
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Screening laboratory values must meet the following criteria (using CTCAE v5.0) and should be obtained within 7 days prior to the randomisation:
- •Polynuclear neutrophils ≥1.5 x 10⁹/L
- •Platelets ≥100 x 10⁹/L
Exclusion Criteria
- •Prior treatment for OPSCC
- •Prior treatment with anti PD-1/PD-L1 and CTLA-4
- •Distant metastases
- •Tumour embolization within 28 days prior to the first dose of study drug.
- •Contra-indication(s) to receive high-dose cisplatin as listed in the most updated Summary of Product Characteristics (including creatinine clearance \<60 mL/min, pre-existing hearing loss or neurological disorder)
- •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
- •Current or prior use of immunosuppressive medication within 14 days before the first dose, including intranasal and inhaled corticosteroids or systemic corticosteroids
- •Active or prior documented autoimmune or inflammatory disease within the 2 years prior to start of treatment (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)
- •History of primary immunodeficiency or organ transplant requiring immunosuppressive drugs
- •Patients with a known HIV, active hepatitis B or C infection
Arms & Interventions
Experimental arm
Experimental arm with nivolumab 2 infusions (2 weeks apart) before Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7
Intervention: Nivolumab
Experimental arm
Experimental arm with nivolumab 2 infusions (2 weeks apart) before Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7
Intervention: Chemoradiation
Control arm
Control arm: Standard of care chemoradiation for 7 weeks with high-dose cisplatin (100 mg/m²) at week 1, 4 and 7
Intervention: Chemoradiation
Outcomes
Primary Outcomes
The rate of patients that fulfill the 3 or 5 conditions as described below (Feasibility assessment of nivolumab neoadjuvant treatment before chemoradiation)
Time Frame: Between baseline and until 3 months (at the end of chemoradiation)
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) 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
Secondary Outcomes
- Locoregional control (LRC)(Between baseline and 2 years after the end of chemoradiation)
- The incidence of Adverse Events related or not related to chemoradiation and Nivolumab(During treatment phase and until 90 days after the last fraction of radiotherapy)
- Overall Survival (OS)(Between baseline and 2 years after the end of chemoradiation)
- Progression-Free Survival (PFS)(Between baseline and 2 years after the end of chemoradiation)
- Objective Response Rate in the experimental arm(Between baseline and up to 17 days after the second infusion of nivolumab)
- Tumor Response in both arms(Between baseline and 3 months after the end of chemoradiation)