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

NCT ID: NCT03803774

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-25
• Study Completion Date: 2026-07-09

Brief 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

Locally Recurrent Head and Neck Squamous Cell Carcinoma; Nasopharyngeal Squamous Cell Carcinoma; Sinonasal Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (IMRRT, birinapant)

Beginning on day 1, patients undergo IMRRT 5 days a week (Monday-Friday). Patients also receive birinapant 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.

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo biopsy

Birinapant

Intervention Type: DRUG

Given IV

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT scan

Intensity-Modulated Radiation Therapy

Intervention Type: RADIATION

Undergo IMRRT

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type: PROCEDURE

Undergo PET scan

Interventions

Biopsy Procedure

Undergo biopsy

Intervention Type: PROCEDURE

Birinapant

Given IV

Intervention Type: DRUG

Computed Tomography

Undergo CT scan

Intervention Type: PROCEDURE

Intensity-Modulated Radiation Therapy

Undergo IMRRT

Intervention Type: RADIATION

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type: PROCEDURE

Other Intervention Names

Biopsy; BIOPSY_TYPE; Bx; TL32711; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; tomography; IMRT; Intensity modulated radiation therapy (procedure); Intensity Modulated RT; Intensity-Modulated Radiotherapy; Radiation, Intensity-Modulated Radiotherapy; Magnetic Resonance; Magnetic Resonance Imaging (MRI); Magnetic resonance imaging (procedure); Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI; MRI Scan; MRIs; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Structural MRI; Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron emission tomography (procedure); Positron Emission Tomography Scan; Positron-Emission Tomography; PT

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed locally recurrent HNSCC, including nasopharyngeal or sinonasal cancer for whom re-irradiation for local control is considered standard of care
• Patients with human papillomavirus (HPV)-negative or HPV-positive head and neck cancer are eligible
• Patients who have had prior treatment with immune therapies are eligible
• Patients must have received curative-intent platinum- and/or cetuximab-based chemoradiotherapy or radiotherapy alone
• Patients must have completed their last treatment dose with chemotherapy or immunotherapy at least 4 weeks (6 weeks for nitrosoureas or mitomycin C) before enrolling on study
• Patients must have completed their last treatment dose with radiotherapy at least 6 months before enrolling on study
• Patients who have had major surgery must be fully recovered and require a recovery period of at least 4 weeks prior to enrolling on study
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Hemoglobin >= 9 g/dL (transfusion permitted)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within 1.5 x the upper limit of normal (ULN) institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Serum creatinine =< 1.5 x upper limit of normal (ULN), OR: Creatinine clearance >= 50 mL/min according to Cockcroft Gault formula or other institutional methods
• Patients must have a corrected QT interval by Fridericia (QTcF) =< 480 msec
• International normalized ratio (INR) =< 1.5 and no clinically significant bleeding event within the past six months
• Ability to understand and the willingness to sign a written informed consent document
• Patients must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• The effects of birinapant on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) beginning at study entry and for the duration of study participation. Male study participants should use an additional barrier method of contraception for 30 days following the last dose of birinapant. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

Exclusion Criteria

• Eligibility for curative-intent surgery, unless the patient is considered a poor surgical candidate related to resectability, functional outcome, or prefers non-surgical therapy
• More than 2 lines of palliative systemic therapy (platinum-, taxane- or cetuximab-based chemotherapy or immunotherapy)
• Patients who are receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to birinapant
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because birinapant may have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with birinapant, breastfeeding should be discontinued prior to enrollment. A negative pregnancy test is required for women of childbearing potential. Women who are postmenopausal (age-related amenorrhea >= 12 consecutive months, or who had undergone hysterectomy or bilateral oophorectomy are exempt from pregnancy testing. If necessary, to confirm postmenopausal status, a follicle stimulating hormone (FSH) level may be included at screening
• Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with birinapant
• Patients requiring the use of anti-tumor necrosis factor (anti TNF) therapies, such as infliximab, or patients who have received treatment with anti-TNF therapies within 5 half-lives of the drug (48 days for infliximab, 55 days for golimumab, 70 days for certolizumab and adalimumab, and 16 days for etanercept)
• Patients with previous exposure to birinapant

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vassiliki Saloura

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute LAO

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Los Angeles General Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Moffitt Cancer Center-International Plaza

Tampa, Florida, United States

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

University of Kansas Clinical Research Center

Fairway, Kansas, United States

HaysMed

Hays, Kansas, United States

University of Kansas Cancer Center

Kansas City, Kansas, United States

Lawrence Memorial Hospital

Lawrence, Kansas, United States

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

Mercy Hospital Pittsburg

Pittsburg, Kansas, United States

Salina Regional Health Center

Salina, Kansas, United States

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, United States

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

NCI - Center for Cancer Research

Bethesda, Maryland, United States

University Health Truman Medical Center

Kansas City, Missouri, United States

University of Kansas Cancer Center - North

Kansas City, Missouri, United States

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, United States

NYU Langone Hospital - Long Island

Mineola, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Wake Forest Baptist Health - Wilkes Medical Center

Wilkesboro, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2019-00175

Identifier Type: REGISTRY

Identifier Source: secondary_id

19-C-0041

Identifier Type: -

Identifier Source: secondary_id

10184

Identifier Type: OTHER

Identifier Source: secondary_id

10184

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2019-00175

Identifier Type: -

Identifier Source: org_study_id

NCT03809208

Identifier Type: -

Identifier Source: nct_alias