head and neck squamous cell carcinoma
Conditions
Interventions
Patients will be treated with
- 2x nivolumab 240 mg flat dose, weeks 1 and 3, OR
- the combination of 1x ipilimumab 1 mg/kg + nivolumab 240 mg flat dose in week
1 and nivolumab mono-therapy 240 mg
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. No immunosuppressive medications prior study inclusion, adults age > 18 years, and 2. Histologically confirmed T3-4N0-3M0 HNSCC (with soft tissue infiltration depth of * 1 cm) of the oral cavity, oropharynx, hypopharynx or supraglottic larynx, eligible for curative surgery as primary treatment or salvage surgery after failed (chemo)radiation. 3. WHO 0-1
Exclusion criteria
Exclusion criteria: - Distant metastasis - Autoimmune disease - A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. - Prior systemic treatment with immunotherapy targeting T-cell costimulation or immune checkpoint pathways; - Hepatitis B / C, HIV or (AIDS); - Pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints: - Phase Ib: Primary endpoint is measured as the number of patients that will not endure a delay in surgery (surgery should be performed in week 5-6) due to neoadjuvant immunotherapy (nivolumab, ipilimumab) related toxicity (measured in terms of SAEs and CTCAE v4.0) OR toxicity due to the treatment of immunotherapy related toxicity (ie high dose corticosteroids)**. ** To meet this endpoint, all patients will be discussed in our immunotherapy team meeting (consisting of at least medical oncologist and head and neck surgeon) the week before surgery, to evaluate whether immunotherapy-related toxicity or treatment of immunotherapy-related toxicity will lead to delay in surgery or not. ** Delay in surgery due to logistical problems (i.e. no IC bed after surgery) or other co-morbidity (i.e. bacterial pneumonia) will not be considered dose-limiting toxicity. - Phase II: Tumor response to neoadjuvant IT in terms of tumor tissue pathological response5 at time of surgery compared to RECIST 1.1 (FDG-PET and perfusion and diffusion weighted MRI). - Phase Ib/II: Primary read-out will also be to explore the potential impact of local tumor hypoxia on tumor T-cell abundance and capacity before and after neo-adjuvant immunotherapy, through HX4-PET-guided tumor biopsies1,2 from hypoxic and normoxic tumor3 regions and subsequent immunological analyses4. NB: 1: Tumor biopsies will be taken -before and after neoadjuvant immunotherapy- guided by hypoxia(HX4)-PET images. All scans will be made in irradiation-mask to ensure spatial correlation between HX4-PET, MRI and FDG-PET. Prior to the biopsy procedure a 3D-model of the tumor and surrounding structures will be generated based on MRI. Within the tumor model the HX4-PET will be visualized as hypoxic and normoxic subregions. The 3D model will be available in the OR, and can be used as a visual guidance to determine biopsy locations (collaboration with Jasper Nijkamp). If possible, for spatiot | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: - We will monitor immune cell subsets and cytokines in the peripheral blood compartment. - Rate and type of late AEs (NCI CTCAE v 4.0) up to 2 years FU after SOC (see Figure 1). - Relapse free survival (RECIST 1.1) and overall survival at 2 years follow-up. | — |
Countries
Netherlands
Outcome results
None listed