Induction and Maintenance Treatment With PARP Inhibitor and Immunotherapy in HPV-negative HNSCC

Sponsor
Gruppo Oncologico del Nord-Ovest
Study ID
NCT04681469
Phase
PHASE2
Status
Recruiting
Apply to this trial

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Niraparib — DRUG
    For all patient's population: * Niraparib 200 mg/day: day -49 to day -21; * Dostarlimab 500 mg iv: day -49 and day -28; At day -21, clinical evaluation will be performed and the patient will be directed to surgery with exclusion from the study in case of progressive disease. Radiological assessment will be performed according to the physician's judgement. If no clinical evidence of disease progression: * Niraparib 200 mg/day: day -21 to day -7 * Dostarlimab 500 mg iv: day -7 * Radiological assessment (day -1, ± 3 days), * Surgery (original margin) at day 0 (±3 days) * Standard postoperative (chemo)radiotherapy according to pathologic report; * Maintenance Niraparib, 200 mg/day for 6 months * Maintenance Dostarlimab, 500 mg iv q3W for the first four cycles and 1000 mg iv Q6W thereafter for 3 months.

Study Details

We propose a window of opportunity trial to evaluate safety and efficacy of a short course of the study combination, composed by an Anti-PD-1 monoclonal antibody (Dostarlimab (TSR-042)) and a PARPi (Niraparib). The study population will be surgically resectable, HPV-negative (defined by p16 negative status) locally advanced HNSCC. Maintenance treatment will be then delivered, so to better integrate the therapeutic benefits of this drug combination. Response to neoadjuvant treatment will be evaluated by the rate of major pathologic response, morphologic, and functional imaging (MRI with functional evaluation -DWI). We anticipate that neoadjuvant and maintenance PARPi plus immunotherapy treatment could lead to a reduction of loco-regional recurrence (LRR) and distant metastasis (DM) rates in such a high-risk population. Furthermore, the window of opportunity portion of this trial will allow in vivo acquisition of valuable knowledge on mechanisms of action and primary resistance to Anti-PD-1 monoclonal antibody and PARPi in HNSCC. In this phase of the study, biological specimens will be collected (pre-treatment tumor biopsy, tissues from the surgical specimen, liquid biopsy, blood and saliva samples) as well as functional imaging (MRI).

Key Dates

Start date
Feb 8, 2021
Status verified
Aug 2022
Primary completion
Jun 30, 2023
Completion
Jun 30, 2028

Study Design

Enrollment
49 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Single Arm Treatment
    For all patient's population: * Niraparib 200 mg/day: day -49 to day -21; * Dostarlimab 500 mg iv: day -49 and day -28; At day -21, clinical evaluation will be performed and the patient will be directed to surgery with exclusion from the study in case of progressive disease. Radiological assessment will be performed according to the physician's judgement. If no clinical evidence of disease progression: * Niraparib 200 mg/day: day -21 to day -7 * Dostarlimab 500 mg iv: day -7 * Radiological assessment (day -1, ± 3 days), * Surgery (original margin) at day 0 (±3 days) * Standard postoperative (chemo)radiotherapy according to pathologic report; * Maintenance Niraparib, 200 mg/day for 6 months * Maintenance Dostarlimab, 500 mg iv q3W for the first four cycles and 1000 mg iv Q6W thereafter for 3 months.

Primary Outcome Measure

Rate of Major Pathological Response (Treatment Activity) [ Time Frame: Day 0, at surgery ]

Central Contacts

Related Studies