Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma
3 other identifiers
interventional
13
1 country
33
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Sep 2019
Longer than P75 for phase_1
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2019
CompletedFirst Posted
Study publicly available on registry
January 15, 2019
CompletedStudy Start
First participant enrolled
September 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 15, 2023
CompletedResults Posted
Study results publicly available
July 23, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
July 9, 2026
ExpectedApril 29, 2026
January 1, 2026
4.1 years
January 14, 2019
July 1, 2024
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention
Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A DLT is defined as any of the following adverse events possibly attributed to the combination of birinapant and radiotherapy that occur within 42 days after treatment. Any grade 5 toxicities. Any grade ≥ 4 hematologic toxicity, except lymphopenia. Any grade ≥ 3 non-hematologic toxicity except for nausea or vomiting managed with supportive care over 2 weeks. ≥ grade 3 prolonged (\> 7 days) serum amylase or lipase elevation, aspartate aminotransferase elevation, and/or alanine aminotransferase elevation. Any grade toxicity that mandates discontinuation of birinapant treatment for more than 2 weeks. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Up to 42 days post-treatment
Maximum Tolerated Dose (MTD) of Birinapant
MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting- toxicity (DLT) during 42 days after the start of therapy, and the dose below that at which at least 2 (of =\< 6) participants have DLT as a result of the drug. A DLT is defined as any of the following adverse events possibly attributed to the combination of birinapant and radiotherapy that occur within 42 days after treatment. Any grade 5 toxicities. Any grade ≥ 4 hematologic toxicity except lymphopenia. Any grade ≥ 3 non-hematologic toxicity except for nausea or vomiting managed with supportive care over 2 weeks. ≥ grade 3 prolonged (\> 7 days) serum amylase or lipase elevation, aspartate aminotransferase elevation, and/or alanine aminotransferase elevation. Any grade toxicity that mandates discontinuation of birinapant treatment for more than 2 weeks. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Up to 42 days
Secondary Outcomes (11)
Response Rate
From the start of the treatment until response assessment by positron emission tomography (PET)-computed tomography (CT), assessed at 3 months post-treatment
Local-regional Control
Up to 24 months post-treatment
Progression-free Survival (PFS)
From start of treatment to time of progression or death, whichever occurs first, assessed up to 24 months post-treatment
Overall Survival (OS)
Up to 24 months post-treatment
Fas-associated Protein With Death Domain (FADD) Copy Gain in Tumor Tissue and/or in Blood Associated With Response
At baseline
- +6 more secondary outcomes
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
An average of 611 days.
Study Arms (1)
Treatment (IMRRT, birinapant)
EXPERIMENTALBeginning 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.
Interventions
Undergo biopsy
Undergo CT scan
Undergo IMRRT
Undergo MRI
Undergo PET scan
Eligibility Criteria
You may qualify if:
- 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
- +5 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
HaysMed
Hays, Kansas, 67601, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Lawrence Memorial Hospital
Lawrence, Kansas, 66044, United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
Mercy Hospital Pittsburg
Pittsburg, Kansas, 66762, United States
Salina Regional Health Center
Salina, Kansas, 67401, United States
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
NCI - Center for Cancer Research
Bethesda, Maryland, 20892, United States
University Health Truman Medical Center
Kansas City, Missouri, 64108, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Wake Forest Baptist Health - Wilkes Medical Center
Wilkesboro, North Carolina, 28659, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Vassiliki Saloura
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Vassiliki Saloura
National Cancer Institute LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 14, 2019
First Posted
January 15, 2019
Study Start
September 25, 2019
Primary Completion
November 15, 2023
Study Completion (Estimated)
July 9, 2026
Last Updated
April 29, 2026
Results First Posted
July 23, 2024
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.