NCT03003637

ImmunoModulation by the Combination of Ipilimumab and Nivolumab Neoadjuvant to Surgery In Advanced or Recurrent Head and Neck Carcinoma

ImmunoModulation by the Combination of Ipilimumab and Nivolumab Neoadjuvant to Surgery In Advanced Or Recurrent Head and Neck Carcinoma. Subtitle: Hypoxia as a Determinant for the Effect of Nivolumab With or Without Ipilimumab on Intra-tumoral T Cell Capacity

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase IB/II trial to examine feasibility and safety of checkpoint blockade (aPD1 with or without aCTLA4) neoadjuvant to standard of care (SOC) in advanced stage head and neck squamous cell carcinoma (HNSCC), a patient population in need for improved clinical outcome and in tumors likely to respond to neoadjuvant aPD1 and aCTLA4. In addition, with this research protocol the potential impact of intratumoral hypoxia on tumor infiltrating lymphocyte (TIL) abundance, differentiation and effector function will be assessed, and the potentially divergent effects of T cell checkpoint blockade in areas of hypoxia and normoxia.

Detailed description

The phase Ib is designed as 3 + 3, with primary objective feasibility and toxicity. Of Note: endpoints must be reached in all 6 patients of cohort 1 and 2, before start of the next cohort. The phase II is designed as a single arm design with primary endpoint efficacy. In phase Ib, two cohorts will be used (cohort 1: nivolumab only and cohort 2: nivolumab and ipilimumab neoadjuvant to surgery) to define which neoadjuvant immunotherapy regimen will be taken towards the expansion cohort 3. Thirty-two patients will be treated with nivolumab (240 mg flat dose, week 1 and week 3, twice in total) as a single agent OR the combination of ipilimumab (1 mg/kg) + nivolumab (240mg flat dose) in week 1, and nivolumab 240mg flat dose in week 3, neoadjuvant to SOC (surgery with or without adjuvant (C)RT).

Conditions

• Immunotherapy
• Head and Neck Neoplasms

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab (240 mg flat dose, week 1 and week 3, twice in total) monotherapy, neoadjuvant to SOC (surgery with or without adjuvant (C)RT).
DRUG	Ipilimumab	Ipilimumab (1 mg/kg) only in week 1, in combination with nivolumab (240 mg flat dose, week 1 and week 3, twice in total), neoadjuvant to SOC (surgery with or without adjuvant (C)RT).

Timeline

• Start date: 2017-02-28
• Primary completion: 2019-10-12
• Completion: 2021-02-12
• First posted: 2016-12-28
• Last updated: 2023-10-23

Locations

1 site across 1 country: Netherlands