Tolinapant and Radiation for Cisplatin-Ineligible, Previously Untreated, Locally Advanced Head and Neck Cancer

NCT05245682 | Active Not Recruiting Early Phase 1 Results DMC FDA Drug

• 4 other identifiers: STUDY00002992P30CA138292WINSHIP5380-21NCI-2021-09678
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Head and Neck Carcinoma of Unknown Primary; Locally Advanced Hypopharyngeal Squamous Cell Carcinoma; Locally Advanced Laryngeal Squamous Cell Carcinoma; Locally Advanced Nasopharyngeal Squamous Cell Carcinoma; Locally Advanced Oropharyngeal Squamous Cell Carcinoma; Locally Advanced Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Upon completion of treatment

Study Arms (1)

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.

Drug: Tolinapant; Radiation: Radiation Therapy

Interventions

Tolinapant DRUG

Given PO

Also known as: ASTX660, 1799328-86-1, XIAP/cIAP1 Antagonist ASTX660

Treatment (tolinapant, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT Therapy

Treatment (tolinapant, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• Emory University: lead
• Astex Pharmaceuticals, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

ASTX-660; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Nicole Schmitt
• Organization: Emory University

nicole.cherie.schmitt@emory.edu

404-778-0278

Study Officials

• Nicole C Schmitt, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 18, 2022
• Study Start: February 17, 2022
• Primary Completion: January 15, 2024
• Study Completion (Estimated): July 21, 2026
• Last Updated: January 8, 2026
• Results First Posted: March 17, 2025

Record last verified: 2026-01

Locations

US (1)