Study of Xevinapant With Radiation and Chemotherapy for Patients With Head and Neck Cancer

NCT06110195 | Terminated Phase 1 FDA Drug

• 1 other identifier: IRB23-0294
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the best safe dose of xevinapant that can be given in combination with chemotherapy and radiation in patients with head and neck cancer. Up to 4 doses of xevinapant will be tested in the dose escalation portion of the study. After the best safe dose is found during escalation, an additional group of participants will be enrolled at that dose to learn more about the treatment combination (dose expansion). The main question\[s\] it aims to answer are:

• what is the maximum safe dose that can be given
• what dose should be used in subsequent (phase 2) trials Participants will receive xevinapant in combination with paclitaxel and carboplatin chemotherapy and radiation. Treatment will be given in 3-week cycles for 3 cycles.

Conditions

Head and Neck Cancer; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (1)

• Determine best safe dose of xevinapant when given in combination with radiation and chemotherapy

  21 days

Secondary Outcomes (6)

• Progression Free Survival

  5 years

• Number of side effects seen when xevinapant is given in combination with radiation and chemotherapy

  21 days

• Overall Survival

  5 years

• Locoregional failure

  5 years

• Distant Failure

  5 years

Study Arms (5)

Escalation Group Dose Level -1

EXPERIMENTAL

Participants assigned to this cohort will receive xevinapant 50 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT). An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Drug: Xevinapant; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Escalation Group Dose Level 0

EXPERIMENTAL

Participants assigned to this cohort will receive xevinapant 100 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT). An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Drug: Xevinapant; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Escalation Group Dose Level 1

EXPERIMENTAL

Participants assigned to this cohort will receive xevinapant 150 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT). An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Drug: Xevinapant; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Escalation Group Dose Level 2

EXPERIMENTAL

Participants assigned to this cohort will receive xevinapant 200 mg for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT). An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Drug: Xevinapant; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Dose Expansion

EXPERIMENTAL

Participants assigned to this cohort will receive xevinapant at the dose found during escalation phase of study for 2 out of every 3 weeks (Daily on days 1-14 of a 21-day cycle). They will also receive carboplatin and paclitaxel weekly for 7 doses with radiation (chemoRT). An additional 3 cycles of xevinapant will be given after completion of chemoRT.

Drug: Xevinapant; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Interventions

Xevinapant DRUG

Given orally during study treatment on days 1-14 of a 21-day treatment cycles. It will be given continuously during treatment with carboplatin, paclitaxel, and radiation (chemoRT). After completely of the chemoRT dosing, an additional 3 cycles of Xevinapant along will be given.

Dose Expansion; Escalation Group Dose Level -1; Escalation Group Dose Level 0; Escalation Group Dose Level 1; Escalation Group Dose Level 2

Carboplatin DRUG

Given with radiation weekly for 7 doses.

Dose Expansion; Escalation Group Dose Level -1; Escalation Group Dose Level 0; Escalation Group Dose Level 1; Escalation Group Dose Level 2

Paclitaxel DRUG

Given with radiation weekly for 7 doses.

Dose Expansion; Escalation Group Dose Level -1; Escalation Group Dose Level 0; Escalation Group Dose Level 1; Escalation Group Dose Level 2

Radiation Therapy RADIATION

Radiation will be given together with paclitaxel and carboplatin for 7 weeks.

Dose Expansion; Escalation Group Dose Level -1; Escalation Group Dose Level 0; Escalation Group Dose Level 1; Escalation Group Dose Level 2

Eligibility Criteria

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

You may qualify if:

• Pathologically proven diagnosis of squamous cell carcinoma of the head and neck (HNSCC) of the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, or sinuses.
• Patients with oropharynx cancer need p16 determination by immunohistochemistry (where positive is defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells).
• Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer must be stages T1-2N1-3 or T3-4N0-3 (AJCC 8th edition). Sinus primary must be T4bN0-3 not amenable to surgical resection.
• P16-positive oropharynx cancer patients, stages T1-2N1-3 or T3-4N0-3 (AJCC 8th edition staging).
• The patient has unresected, measurable disease as defined by the presence of at least one measurable lesion per RECIST 1.1.
• Age \>= 18 years of age
• Patients must have a contraindication to cisplatin
• Performance Status of 0-2
• Adequate hematologic function
• White Blood Cell Count (WBC) \>= 2000 cells/mm3
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm3
• Platelets \>= 100,000 cells/mm3
• Hemoglobin \>= 9.0 g/dL
• Adequate renal function was defined as follows: Creatinine clearance (CrCl) \> 30 mL/min
• Adequate hepatic function

You may not qualify if:

• Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.
• Carcinoma of the neck of unknown primary site of origin
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if not within \< 3 years
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
• Severe, active co-morbidity defined as follows:
• History of bone marrow transplant and organ transplant, including allogeneic stem cell transplantation.
• Unstable angina requiring hospitalization in the last 6 months.
• New York Heart Association Functional Classification III/IV.
• Myocardial infarction within the last 6 months.
• Persistent Grade 3-4 electrolyte abnormalities that cannot be reversed despite as indicated by repeat testing.
• Ongoing active infection associated with symptoms and/or requires antibiotic therapy at the time of initiation of treatment.
• Pregnancy and nursing females, if applicable.
• Receipt of live vaccinations within 28 days prior to study start.
• Patients who are receiving any other investigational agents.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.

Sponsors & Collaborators

• University of Chicago: lead
• EMD Serono: collaborator

Study Sites (1)

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Carboplatin; Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Therapeutics

Study Officials

• Ari Rosenberg, ND

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2023
• First Posted: October 31, 2023
• Study Start: January 24, 2024
• Primary Completion: May 12, 2025
• Study Completion: May 12, 2025
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (1)