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Active Not RecruitingNCT03803774

Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma

Birinapant and Intensity Modulated Re-Irradiation Therapy (IMRRT) for Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)

Status
Active Not Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
13 (actual)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I trial studies the side effects and best dose of birinapant when given together with intensity modulated re-irradiation therapy (IMRRT) in treating patients with head and neck squamous cell carcinoma that has come back at or near the same place as the original (primary) tumor (locally recurrent). Birinapant may stop the growth of tumor cells by blocking inhibitor of apoptosis (IAP), a protein needed for tumor cell survival. IMRRT uses thin beams of radiation of different intensities that are aimed at the tumor from many angles. This type of re-irradiation therapy reduces the damage to healthy tissue near the tumor. Giving birinapant with IMRRT may lower the chance of head and neck squamous cell carcinoma growing or spreading.

Detailed description

PRIMARY OBJECTIVE: I. Determine the toxicities and maximum tolerated dose (MTD) of birinapant concurrent with intensity modulated re-irradiation therapy (IMRRT). SECONDARY OBJECTIVES: I. Determine the objective response rate of patients with locoregionally recurrent head and neck squamous cell carcinoma (HNSCC) treated with re-irradiation and birinapant. II. Determine the local-regional control, progression free survival (PFS), and overall survival. III. Determine if Fas-associated death domain (FADD) and/or Baculoviral IAP Repeat containing 2 and Baculoviral IAP Repeat containing 3 (BIRC2/3) copy gain in tumor tissue or in the blood are associated with improved response, locoregional control (LCR), progression-free survival and overall survival. IV. Determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers in tumor tissue, by using microwestern to assess decrease in drug targets inhibitor of apoptosis 1/2 (IAP1/2) and increase in apoptosis/necroptosis markers caspase 3 and mixed lineage kinase domain like pseudokinase gene (MLKL). EXPLORATORY OBJECTIVES: I. Explore if mutational load detected with whole exome sequencing of tumor tissue influences objective response rate. II. Explore if programmed death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8) T-cell tumor infiltration, TNFalphatumor necrosis factor (TNF)alpha, and other immune related biomarkers in tumor tissue are associated with objective response rate. III. Explore the pharmacokinetics of birinapant in combination with radiotherapy in blood samples. IV. Explore whether specific germline single-nucleotide polymorphisms (SNPs) are associated with response to birinapant and reirradiation. OUTLINE: This is a dose-escalation study of birinapant. Beginning on day 1, patients undergo IMRRT 5 days a week (Monday-Friday). Patients also receive birinapant intravenously (IV) over 30 minutes on days 2 and 9 of each cycle. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days, and at 3, 6, 9, 12, 18, and 24 months until confirmation of disease progression.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsy ProcedureUndergo biopsy
DRUGBirinapantGiven IV
PROCEDUREComputed TomographyUndergo CT scan
RADIATIONIntensity-Modulated Radiation TherapyUndergo IMRRT
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREPositron Emission TomographyUndergo PET scan

Timeline

Start date
2019-09-25
Primary completion
2023-11-15
Completion
2026-07-09
First posted
2019-01-15
Last updated
2025-11-10
Results posted
2024-07-23

Locations

33 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03803774. Inclusion in this directory is not an endorsement.