Birinapant and Intensity Modulated Re-Irradiation Therapy for Local-Regionally Recurrent Head and Neck Squamous Cell Carcinoma

Oral Cancer Clinical Trial

Official title: A Phase I Study of Birinapant and Intensity Modulated Re-Irradiation Therapy (IMRRT) for Local-Regionally Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)

Status Recruiting

Clinical Trial Summary

Background:

Head and neck cancer is a group of cancers that start in the mouth, nose, throat, larynx and sinuses. The usual treatment is surgery, radiation, chemotherapy, or a combination of those. Approximately 50% of HPV-negative head and neck cancer patients that have been treated with any of these modalities will have a recurrence. For these patients, current treatment options include surgery and re-irradiation with chemotherapy, which can reduce symptoms and may stop the tumor from growing but in the majority of cases, only for a few months. In this trial, researchers want to see if they can cure or significantly lower the chance of head and neck cancer growing back or spreading by adding the new agent birinapant to re-irradiation.

Objective:

To test the safety of birinapant and re-irradiation at different doses in patients with head and neck cancer.

Eligibility:

Adults age 18 and older with head and neck cancer who are candidates for re-irradiation.

Design:

Participants will be screened with a review of their medical record. Participants will have exams and procedures that are part of their usual care. Participants will also have a test of heart activity before treatment.

Participants will have urine pregnancy tests, if female.

Participants will have blood and tumor samples taken 2 times and stored for research. The study lasts 6 weeks.

Participants will get radiation for 5 days a week (Monday Friday) for all 6 weeks.

Participant will get the study drug on 4 Tuesdays. They will get it in an arm vein over 30 minutes each time.

About 4 weeks after the study ends, participants will have a follow-up visit. They will have a physical exam, health questions, and blood tests.

Participants may have scans 4 times over the next 2 years. Participants will get an email or phone call every 6 months.

Sponsoring Institute: National Cancer Institute

Clinical Trial Description

Background:

• Head and neck squamous cell carcinomas (HNSCC) affect 52,000 new patients and cause approximately 11,000 deaths in the U.S. annually.

• The Cancer Genome Atlas recently uncovered amplifications of chromosome 11q13/22 in approximately 30% of HNSCC.

• The 11q13/22 loci harbor genes Fas Associated Death Domain (FADD) and Baculovirus Inhibitor of apoptosis Repeat Containing (BIRC2/cIAP1). A mutually exclusive subset harboring mutation of caspase 8 (CASP8) affects an additional 10% of HPV- cases. Further, deletions in Tumor Necrosis Factor Associated Factor 3 and overexpression of BIRC3 (cIAP2) are detected in 20% of HPV+ HNSCC.

• These genes encode proteins that form critical components of the Tumor Necrosis Factor Receptor/Death Domain Receptor signaling complex, which is deregulated and implicated in cell survival and therapeutic resistance in cancer.

• Based on pre-clinical studies, birinapant plus radiation demonstrates anti-tumor activity and improved survival, but the dose, schedule and tolerability in human studies needs to be determined.

Objectives:

-The primary objective is to determine the toxicities and maximum tolerated dose (MTD) of birinapant concurrent with IMRRT

Eligibility:

-Patients must have histologically or cytologically confirmed locally recurrent HNSCC for whom re-irradiation for local control is considered standard of care.

Design:

-Birinapant dose levels include 5.6, 11, 17 and 24mg/m2 IV on days 2 and 9 of each cycle. The primary endpoints are acute toxicities and the MTD for 2/3 week and weekly administration schedule of birinapant plus re-IMRT. Secondary clinical endpoints include overall response by PET- CT and RECIST criteria at 2 months post treatment, delayed toxicities, duration of local and regional control, progression free survival (PFS), Overall Survival (OS), and Whole ExomeSequencing of tumor biopsies. Exploratory endpoints are FADD and BIRC2 copy number. ;

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Facial Cancer
• Head and Neck Neoplasms
• Head Cancer
• Mouth Neoplasms
• Neck Cancer
• Oral Cancer
• Squamous Cell Carcinoma of Head and Neck
• Upper AerodigestiveTract Cancer

• NCT number: NCT03809208
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Elizabeth Q Akoth
• Phone: (240) 858-3154
• Email: elizabeth.akoth@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: April 15, 2019
• Completion date: October 31, 2021