NCT05245682

Tolinapant and Radiation for Cisplatin-Ineligible, Previously Untreated, Locally Advanced Head and Neck Cancer

Early-Phase Open-label Study of Tolinapant and Radiation in Cisplatin-Ineligible Patients With Previously Untreated, Locally Advanced Head and Neck Cancer

• Status: Active Not Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This early-phase trial tests the safety and side effects of a tolinapant given together with radiation therapy in treating patients with head and neck cancer for which the patient has not received treatment in the past (previously untreated), has spread to nearby tissue or lymph nodes (locally advanced) and cannot receive cisplatin (cisplatin-ineligible). Tolinapant may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving tolinapant and radiation therapy may kill more tumor cells.

Detailed description

Primary Objective: To evaluate the safety and tolerability of the recommended phase 2 dose (RP2D) of tolinapant when given in combination with radiation. Secondary Objectives: To assess preliminary efficacy of the combination of tolinapant and radiation in cisplatin ineligible patients with head and neck cancer as determined by locoregional control, two year progression-free survival (PFS), and two-year overall survival (OS). Exploratory Objective: To compare immune cell infiltrates following the first cycle of tolinapant + radiation, compared with baseline biopsy tissue and peripheral blood. TERTIARY/EXPLORATORY OBJECTIVES: I. To assess the effects of the combination of tolinapant + radiation on immune cells in blood and tumor. II. To assess the association between immune responses and FADD expression in tumors. OUTLINE: Patients undergo standard of care radiation therapy for a total of 35 fractions over 6-7 weeks and receive tolinapant orally (PO) daily for 7 days during weeks 1, 3, 5, and 7 of radiation therapy in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up 1, 3, 6, 12, and 24 months.

Conditions

• Head and Neck Carcinoma of Unknown Primary
• Locally Advanced Head and Neck Squamous Cell Carcinoma
• Locally Advanced Hypopharyngeal Squamous Cell Carcinoma
• Locally Advanced Laryngeal Squamous Cell Carcinoma
• Locally Advanced Nasopharyngeal Squamous Cell Carcinoma
• Locally Advanced Oropharyngeal Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Tolinapant	Given PO
RADIATION	Radiation Therapy	Undergo radiation therapy

Timeline

• Start date: 2022-02-17
• Primary completion: 2024-01-15
• Completion: 2026-07-21
• First posted: 2022-02-18
• Last updated: 2026-01-08
• Results posted: 2025-03-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study