Locally Recurrent Head and Neck Squamous Cell CarcinomaPhase 1NCT03803774
Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma
A Phase 1 study testing Biopsy Procedure, Birinapant and Computed Tomography in people with Locally Recurrent Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 33 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Recurrent Head and Neck Squamous Cell Carcinoma, Nasopharyngeal Squamous Cell Carcinoma, Sinonasal Squamous Cell Carcinoma
- What is being tested?
- Biopsy Procedure, Birinapant and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 33 sitesUnited States
- Study dates
- 25 Sep 2019to 9 Jul 2027
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
33 sites in 1 country.
33 sites in 1 country
United States33 sites
NCI - Center for Cancer Research
Bethesda, Maryland, 20892
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
HaysMed
Hays, Kansas, 67601
University of Kansas Cancer Center
Kansas City, Kansas, 66160
University Health Truman Medical Center
Kansas City, Missouri, 64108
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Los Angeles General Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116
The University of Kansas Cancer Center - Olathe
Olathe, Kansas, 66061
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Mercy Hospital Pittsburg
Pittsburg, Kansas, 66762
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Salina Regional Health Center
Salina, Kansas, 67401
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612
Moffitt Cancer Center
Tampa, Florida, 33612
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Wake Forest Baptist Health - Wilkes Medical Center
Wilkesboro, North Carolina, 28659
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Birinapant and Intensity Modulated Re-Irradiation Therapy (IMRRT) for Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)
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.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the toxicities and maximum tolerated dose (MTD) of birinapant concurrent with intensity modulated re-irradiation therapy (IMRRT).
SECONDARY OBJECTIVES:
- 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:
- 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
- Being tested
- Biopsy Procedure, Birinapant, Computed Tomography, Intensity-Modulated Radiation Therapy, Magnetic Resonance Imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
BirinapantDrug
Also called TL32711
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy
Undergo IMRRT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET scan
| Study group | Role | What they receive |
|---|---|---|
| Treatment (IMRRT, birinapant) | Experimental | 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. Receives: Procedure: Biopsy Procedure; Drug: Birinapant; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 42 days
Secondary outcomes (11)
Response Rate
Overall response is the best response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Estimates of response rates will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort and will be presented along with a 95% two-sided confidence interval. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesion. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions; and the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: 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
Estimates of local control will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort and will be presented along with a 95% two-sided confidence interval.
Measured: Up to 24 months post-treatment
Progression-free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Estimates of PFS will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort and will be presented along with a 95% two-sided confidence interval. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions; and the appearance of one or more new lesions.
Measured: From start of treatment to time of progression or death, whichever occurs first, assessed up to 24 months post-treatment
Overall Survival (OS)
OS is the time between the first day of treatment to the day of death. Estimates of OS will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort, and will be presented along with a 95% two-sided confidence interval.
Measured: 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
The association between FADD copy gain in tumor tissue and/or in blood will be evaluated for any association with response.
Measured: At baseline
BIRC2 Copy Gain in Tumor Tissue and/or in Blood Associated With Response
BIRC2 copy gain in tumor tissue and/or in blood will be evaluated for any association with response.
Measured: At baseline
Baculoviral Inhibitor of Apoptosis (IAP) Repeat Containing 2 and Baculoviral IAP Repeat Containing 2/3 (BIRC2/3) Copy Gain in Tumor Tissue and/or in Blood
Baculoviral inhibitor of apoptosis (IAP) Repeat containing 2 and Baculoviral IAP Repeat containing 2/3 (BIRC2/3) copy gain in tumor tissue and/or in blood.
Measured: At baseline
Feasibility of Detecting Effects of Birinapant and Re-irradiation on Pilot Pharmacodynamic Markers in Tumor Tissue
Will determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers in tumor tissue.
Measured: Up to cycle 1, day 4
Feasibility of Detecting Effects of Birinapant and Re-irradiation on Pilot Pharmacodynamic Markers Microwestern for Decrease in Drug Targets Inhibitor of Apoptosis 1/2 (IAP1/2)
Will determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers microwestern for decrease in drug targets IAP1/2.
Measured: Up to cycle 1, day 4
Change in Caspase 3 Levels
A change (i.e., increase) in apoptosis/necroptosis marker caspase 3 will be evaluated.
Measured: Baseline up to cycle 1, day 4
Change in Mixed Lineage Kinase Domain-like (MLKL) Levels
A change (i.e., increase) in apoptosis/necroptosis marker mixed lineage kinase domain-like (MLKL) levels will be evaluated.
Measured: Baseline up to cycle 1, day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2019
- Study start25 Sep 2019
- Primary completion15 Nov 2023
- Study completion9 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Recurrent Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Vassiliki Saloura, Principal investigator, National Cancer Institute LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03803774
- Sponsor's protocol ID
- NCI-2019-00175
- Other IDs
- NCI-2019-00175, 19-C-0041, 10184, 10184
- Status last verified
- Jul 2026
- First submitted
- 14 Jan 2019
- Last updated
- 3 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Birinapant and Intensity Modulated Re-Irradiation Therapy (IMRRT) for Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT03803774
- Acronym / sponsor ID
- NCI-2019-00175
- Conditions
- Locally Recurrent Head and Neck Squamous Cell Carcinoma, Nasopharyngeal Squamous Cell Carcinoma, Sinonasal Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 25 Sep 2019 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 9 Jul 2027 (estimated)
- First posted
- 15 Jan 2019 (actual)
- Results
- Posted 23 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Determine the toxicities and maximum tolerated dose (MTD) of birinapant concurrent with intensity modulated re-irradiation therapy (IMRRT).
SECONDARY OBJECTIVES:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (IMRRT, birinapant) | Experimental | Procedure: Biopsy Procedure, Drug: Birinapant, Procedure: Computed Tomography, Radiation: Intensity-Modulated Radiation Therapy, Procedure: Magnetic Resonance Imaging, Procedure: Positron Emission TomographyBeginning 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo biopsy | Procedure or surgery | Treatment (IMRRT, birinapant) |
| BirinapantAlso: TL32711Given IV | Drug | Treatment (IMRRT, birinapant) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT scan | Procedure or surgery | Treatment (IMRRT, birinapant) |
| Intensity-Modulated Radiation TherapyAlso: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated RadiotherapyUndergo IMRRT | Radiation | Treatment (IMRRT, birinapant) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Treatment (IMRRT, birinapant) |
| Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET scan | Procedure or surgery | Treatment (IMRRT, birinapant) |
Primary outcome
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention
Time frame: Up to 42 days post-treatment
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.
Maximum Tolerated Dose (MTD) of Birinapant
Time frame: Up to 42 days
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.
11 secondary outcomes
Response Rate
Time frame: 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
Time frame: Up to 24 months post-treatment
Progression-free Survival (PFS)
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 24 months post-treatment
Overall Survival (OS)
Time frame: 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
Time frame: At baseline
BIRC2 Copy Gain in Tumor Tissue and/or in Blood Associated With Response
Time frame: At baseline
Baculoviral Inhibitor of Apoptosis (IAP) Repeat Containing 2 and Baculoviral IAP Repeat Containing 2/3 (BIRC2/3) Copy Gain in Tumor Tissue and/or in Blood
Time frame: At baseline
Feasibility of Detecting Effects of Birinapant and Re-irradiation on Pilot Pharmacodynamic Markers in Tumor Tissue
Time frame: Up to cycle 1, day 4
Feasibility of Detecting Effects of Birinapant and Re-irradiation on Pilot Pharmacodynamic Markers Microwestern for Decrease in Drug Targets Inhibitor of Apoptosis 1/2 (IAP1/2)
Time frame: Up to cycle 1, day 4
Change in Caspase 3 Levels
Time frame: Baseline up to cycle 1, day 4
Change in Mixed Lineage Kinase Domain-like (MLKL) Levels
Time frame: Baseline up to cycle 1, day 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vassiliki Saloura principal investigator
National Cancer Institute LAO
33 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biopsy Procedure, Birinapant and Computed Tomography in people with Locally Recurrent Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 33 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention (time frame: Up to 42 days post-treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2026.