Head and Neck Carcinoma of Unknown PrimaryEarly Phase 1NCT05245682
Tolinapant and Radiation for Cisplatin-Ineligible, Previously Untreated, Locally Advanced Head and Neck Cancer
A Early Phase 1 study testing Tolinapant and Radiation Therapy in people with Head and Neck Carcinoma of Unknown Primary and Locally Advanced Head and Neck Squamous Cell Carcinoma, run by Emory University at 1 site in United States.
Trial summary
This early-phase trial tests the safety and side effects of a tolinapant given together with radiation therapy in treating patients with head and neck cancer for which the patient has not received treatment in the past (previously untreated), has spread to nearby tissue or lymph nodes (locally advanced) and cannot… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Carcinoma of Unknown Primary, Locally Advanced Head and Neck Squamous Cell Carcinoma, Locally Advanced Hypopharyngeal Squamous Cell Carcinoma
- What is being tested?
- Tolinapant and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2022to 21 Jul 2027
- Phase
- Early 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
- Male or Female.
- Age ≥18 years.
- ECOG performance status ≤1 (see Appendix A).
- Patients with histologically or cytologically confirmed diagnosis of HNSCC, previously untreated and locally advanced, for whom definitive or adjuvant radiation is planned but cisplatin chemotherapy is contraindicated.
- For the purposes of trial eligibility, anatomic subsites of HNSCC may include the larynx, oropharynx, hypopharynx, nasopharynx, or unknown primary site presenting with neck lymph nodal disease.
- Patients must have a contraindication to cisplatin as defined below. The scores must be recorded on a CRF:
Show all 26Show fewer
- Age ≥ 70 with moderate to severe comorbidity, defined as having one or more of the following conditions within 30 days prior to registration:
- Modified Charlson Comorbidity Index ≥ 1
- ACE-27 Index ≥ 1
- G-8 score ≤ 14
- CARG Toxicity Score ≥ 30%
- CIRS-G Score ≥ 4 -OR-
- Age ≥ 18 with an absolute or relative contraindication to cisplatin, defined as one or more of the following criterion within 30 days prior to registration:
- Pre-existing peripheral neuropathy grade ≥ 1;
- History of hearing loss, defined as either an existing need of a hearing aid OR moderate hearing loss as defined by the American Speech and Hearing Association (pretreatment audiogram showing 40-55 db HL hearing loss)
- Creatinine clearance (CrCl) must be > 30 and < 50 mL/min. For this calculation, use the Cockroft-Gault formula: CrCl = 0.85 (if female)* ((140-Age) / (Serum Creatinine)) * (Weight in kg / 72).
- Acceptable organ function, as evidenced by the following laboratory data:
- Absolute neutrophil count [ANC] ≥ 1,500 cells/l; hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/l.
- Serum creatinine ≤ 1.5 mg/dl, or calculated creatinine clearance ≥ 60 ml/min.
- Bilirubin ≤ upper limit normal [ULN], alanine aminotransferase [ALT] ≤ 1.5 x ULN and/or aspartate aminotransferase [AST] ≤ 1.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN.
- Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 x ULN.
- Activated partial thromboplastin (aPTT) time ≤ 1.5 x ULN. Amylase and lipase ≤ ULN.
- The effects of tolinapant on the developing human fetus are unknown. For this reason and because tolinapant as well as other therapeutic agents used in this trial are known to be teratogenic, females of child-bearing potential (FCBP) must have a negative serum pregnancy test prior to starting therapy.
- Female patients of childbearing potential and men must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study participation and for at least 6 months following study drug discontinuation. 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. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (if age > 55 years); if the female subject is < 55 years and she has been naturally postmenopausal for > 1 year her reproductive status has to be verified by additional lab tests (< 20 estradiol OR estradiol < 40 with FSH > 40 in women not on estrogen replacement therapy).
- Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol specified laboratory tests, other study procedures, and study restrictions.
- Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
Who cannot join
- Patients who have had prior radiotherapy to the head and neck region
- Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tolinapant.
- 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.
- Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure (or ejection fraction <50%); or uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy.
- Contraindications to radiotherapy (e.g. uncontrolled connective tissue disorder).
Show all 16Show fewer
- Women who are pregnant or breast feeding.
- Vulnerable populations including prisoners and adults who are unable to consent.
- Known history of human immunodeficiency virus (HIV) infection, or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
- Grade 3 or greater neuropathy.
- Known distant metastases (i.e., outside of the neck).
- Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.
- Concurrent second malignancy requiring active therapy.
- Patients with a history of allogenic transplant must not have ≥Grade 3 graft-versus-host disease (GVHD) or any clinically significant GVHD requiring systemic immunosuppression.
- Systemic corticosteroids >20 mg daily prednisone equivalent (unless patient has been taking a continuous dose for >3 weeks prior to study entry).
- Medications known to cause QT prolongation including some antipsychotics (chlorpromazine, haloperidol, droperidol, quetiapine, olanzapine, amisulpride, thioridazine), antiarrhythmics (quinidine, procainamide, disopyramide, flecanide, encainide, sotalol, amiodarone), antidipressants (amitriptyline, doxepin, imipramine, nortriptyline, desipramine), mianserin, citalopram, escitalopram, venlafaxine, bupropion, moclobemide), and antihistamines (diphenhydramine, astemizole, loratadine, terfenadine), macrolide antibiotics (erythromycin, clarithromycin), and antimalarials (chloroquine, hydroxychloroquine, quinine), unless the use of these drugs cannot be avoided.
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Early-Phase Open-label Study of Tolinapant and Radiation in Cisplatin-Ineligible Patients With Previously Untreated, Locally Advanced Head and Neck Cancer
This early-phase trial tests the safety and side effects of a tolinapant given together with radiation therapy in treating patients with head and neck cancer for which the patient has not received treatment in the past (previously untreated), has spread to nearby tissue or lymph nodes (locally advanced) and cannot receive cisplatin (cisplatin-ineligible). Tolinapant may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving tolinapant and radiation therapy may kill more tumor cells.
Read the detailed description
Primary Objective:
To evaluate the safety and tolerability of the recommended phase 2 dose (RP2D) of tolinapant when given in combination with radiation.
Secondary Objectives:
To assess preliminary efficacy of the combination of tolinapant and radiation in cisplatin ineligible patients with head and neck cancer as determined by locoregional control, two year progression-free survival (PFS), and two-year overall survival (OS).
Exploratory Objective:
To compare immune cell infiltrates following the first cycle of tolinapant + radiation, compared with baseline biopsy tissue and peripheral blood.
TERTIARY/EXPLORATORY OBJECTIVES:
- To assess the effects of the combination of tolinapant + radiation on immune cells in blood and tumor.
II. To assess the association between immune responses and FADD expression in tumors.
OUTLINE:
Patients undergo standard of care radiation therapy for a total of 35 fractions over 6-7 weeks and receive tolinapant orally (PO) daily for 7 days during weeks 1, 3, 5, and 7 of radiation therapy in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up 1, 3, 6, 12, and 24 months.
- Conditions
- Head and Neck Carcinoma of Unknown Primary, Locally Advanced Head and Neck Squamous Cell Carcinoma, Locally Advanced Hypopharyngeal Squamous Cell Carcinoma, Locally Advanced Laryngeal Squamous Cell Carcinoma, Locally Advanced Nasopharyngeal Squamous Cell Carcinoma, Locally Advanced Oropharyngeal Squamous Cell Carcinoma
- Being tested
- Tolinapant, Radiation Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolinapantDrug
Also called ASTX660, 1799328-86-1, XIAP/cIAP1 Antagonist ASTX660
Given PO
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Radiation, Radiation Therapy, NOS, Radiotherapeutics
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tolinapant, radiation therapy) | Experimental | Patients undergo standard of care radiation therapy for a total of 35 fractions over 7 weeks and receive tolinapant PO daily for 7 days during weeks 1, 3, 5, and 7 of radiation therapy in the absence of disease progression or unacceptable toxicity. Receives: Drug: Tolinapant; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Tolinapant + Radiation (Number of Patients With Adverse Events Per CTCAE v5.0)
Safety will be assessed on clinical examination and measurement of laboratory parameters. All safety assessments including adverse events, clinical laboratory evaluations, and vital signs will be summarized with descriptive statistics, where appropriate, and listed in the data listings using MedDRA terms.
Measured: Up to 60 days post-treatment
Feasibility of Tolinapant + Radiation (Number of Patients Able to Complete Treatment)
Feasibility is defined as completion of treatment, which will be reported as a percentage, with a 95% exact confidence interval using the Clopper-Pearson method.
Measured: Upon completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2022
- Study start17 Feb 2022
- Primary completion15 Jan 2024
- Study completion21 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 Head and Neck Carcinoma of Unknown PrimaryStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Astex Pharmaceuticals, Inc., National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Nicole Schmitt, Emory University
- Investigators
- Nicole C Schmitt, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05245682
- Sponsor's protocol ID
- STUDY00002992
- Other IDs
- P30CA138292, WINSHIP5380-21, NCI-2021-09678
- Status last verified
- Aug 2026
- First submitted
- 11 Jan 2022
- Last updated
- 21 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early-Phase Open-label Study of Tolinapant and Radiation in Cisplatin-Ineligible Patients With Previously Untreated, Locally Advanced Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT05245682
- Acronym / sponsor ID
- STUDY00002992
- Conditions
- Head and Neck Carcinoma of Unknown Primary, Locally Advanced Head and Neck Squamous Cell Carcinoma, Locally Advanced Hypopharyngeal Squamous Cell Carcinoma, Locally Advanced Laryngeal Squamous Cell Carcinoma, Locally Advanced Nasopharyngeal Squamous Cell Carcinoma, Locally Advanced Oropharyngeal Squamous Cell Carcinoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Astex Pharmaceuticals, Inc., National Cancer Institute (NCI)
- Study start
- 17 Feb 2022 (actual)
- Primary completion
- 15 Jan 2024 (actual)
- Study completion
- 21 Jul 2027 (estimated)
- First posted
- 18 Feb 2022 (actual)
- Results
- Posted 17 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This early-phase trial tests the safety and side effects of a tolinapant given together with radiation therapy in treating patients with head and neck cancer for which the patient has not received treatment in the past (previously untreated), has spread to nearby tissue or lymph nodes (locally advanced) and cannot receive cisplatin (cisplatin-ineligible). Tolinapant may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving tolinapant and radiation therapy may kill more tumor cells.
Detailed description
Primary Objective:
To evaluate the safety and tolerability of the recommended phase 2 dose (RP2D) of tolinapant when given in combination with radiation.
Secondary Objectives:
To assess preliminary efficacy of the combination of tolinapant and radiation in cisplatin ineligible patients with head and neck cancer as determined by locoregional control, two year progression-free survival (PFS), and two-year overall survival (OS).
Exploratory Objective:
To compare immune cell infiltrates following the first cycle of tolinapant + radiation, compared with baseline biopsy tissue and peripheral blood.
TERTIARY/EXPLORATORY OBJECTIVES:
- To assess the effects of the combination of tolinapant + radiation on immune cells in blood and tumor.
II. To assess the association between immune responses and FADD expression in tumors.
OUTLINE:
Patients undergo standard of care radiation therapy for a total of 35 fractions over 6-7 weeks and receive tolinapant orally (PO) daily for 7 days during weeks 1, 3, 5, and 7 of radiation therapy in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up 1, 3, 6, 12, and 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tolinapant, radiation therapy) | Experimental | Drug: Tolinapant, Radiation: Radiation TherapyPatients undergo standard of care radiation therapy for a total of 35 fractions over 7 weeks and receive tolinapant PO daily for 7 days during weeks 1, 3, 5, and 7 of radiation therapy 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 (26 listed)
- Male or Female.
- Age ≥18 years.
- ECOG performance status ≤1 (see Appendix A).
- Patients with histologically or cytologically confirmed diagnosis of HNSCC, previously untreated and locally advanced, for whom definitive or adjuvant radiation is planned but cisplatin chemotherapy is contraindicated.
- For the purposes of trial eligibility, anatomic subsites of HNSCC may include the larynx, oropharynx, hypopharynx, nasopharynx, or unknown primary site presenting with neck lymph nodal disease.
Key exclusion criteria (16 listed)
- Patients who have had prior radiotherapy to the head and neck region
- Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tolinapant.
- 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.
- Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure (or ejection fraction <50%); or uncontrolled Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy.
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 |
|---|---|---|
| TolinapantAlso: ASTX660, 1799328-86-1, XIAP/cIAP1 Antagonist ASTX660Given PO | Drug | Treatment (tolinapant, radiation therapy) |
| Radiation TherapyAlso: Cancer Radiotherapy, Radiation, Radiation Therapy, NOS, RadiotherapeuticsUndergo radiation therapy | Radiation | Treatment (tolinapant, radiation therapy) |
Primary outcome
Safety of Tolinapant + Radiation (Number of Patients With Adverse Events Per CTCAE v5.0)
Time frame: Up to 60 days post-treatment
Safety will be assessed on clinical examination and measurement of laboratory parameters. All safety assessments including adverse events, clinical laboratory evaluations, and vital signs will be summarized with descriptive statistics, where appropriate, and listed in the data listings using MedDRA terms.
Feasibility of Tolinapant + Radiation (Number of Patients Able to Complete Treatment)
Time frame: Upon completion of treatment
Feasibility is defined as completion of treatment, which will be reported as a percentage, with a 95% exact confidence interval using the Clopper-Pearson method.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Head and Neck Carcinoma of Unknown Primary
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
Recruiting
Studying the PAGODA Algorithm for Chemotherapy Dose Changes to Prevent Unplanned Treatment Delays
Ampulla of Vater Carcinoma, Appendix Carcinoma
Active, not recruitingPhase 3
Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Neck Squamous Cell Carcinoma of Unknown Primary, Recurrent Hypopharyngeal Squamous Cell Carcinoma
Active, not recruitingPhase 1
Determining the Biodistribution of an Imaging Tracer (68Ga-FAPi-46) in Patients With Solid Tumors or Hematologic Cancers
Anal Carcinoma, Bladder Carcinoma
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.
Nicole C Schmitt, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tolinapant and Radiation Therapy in people with Head and Neck Carcinoma of Unknown Primary and Locally Advanced Head and Neck Squamous Cell Carcinoma, run by Emory University at 1 site 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 26 inclusion and 16 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 21 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 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 17 Mar 2025). 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?
Safety of Tolinapant + Radiation (Number of Patients With Adverse Events Per CTCAE v5.0) (time frame: Up to 60 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 21 Aug 2026.