A Study of Xevinapant With Cisplatin and Radiation Therapy After Surgery in People With Head and Neck Cancer

NCT06145412 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 23-044
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test whether treatment with Xevinapant added to standard chemoradiation after surgery is an effective treatment for people with high-risk head and neck cancers.

Conditions

Head and Neck Cancer

Keywords

Xevinapant; Cisplatin; Radiotherapy; 23-044

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression free survival will be defined as the time from the start of treatment to biopsyproven locoregional recurrence, distant tumor recurrence, or death. For patients without evidence of gross disease at registration, any locoregional progression will be considered a PFS event. For patients with gross disease at registration, progression-free survival will be determined based upon RECIST 1.1 criteria.

  12 months

Secondary Outcomes (1)

• Overall survival

  3 years

Study Arms (1)

Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy

EXPERIMENTAL

The study will consist of three phases: 2) concurrent radiation, cisplatin, and xevinapant, and 3) adjuvant xevinapant. Concurrent Chemoradiation Subjects will undergo FDG PET/CT simulation and standard radiation treatment planning. FDG PET/CT (Simulation or diagnostic) will also be utilized to rule out distant metastases. Subjects who meet criteria for the treatment phase will undergo standard of care adjuvant radiation (60-70 Gy administered in 2 Gy fractions) with concurrent cisplatin (2-3 cycles, with 100mg/m2 per cycle q3 weeks), and xevinapant (oral dose of 200mg per day on days 1-14 every 21 days for 3 cycles) Adjuvant Phase After completion of concurrent chemoradiation, patients will undergo an additional 3 cycles of xevinapant (oral dose of 200mg per day on days 1-14 every 21 days for 3- cycles)

Drug: Xevinapan; Drug: Cisplatin; Radiation: External beam

Interventions

Xevinapan DRUG

Xevinapant (oral dose of 200mg per day on days 1-14 every 21 days for 3 cycles)

Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy

Cisplatin DRUG

Cisplatin (2-3 cycles, with 100mg/m2 per cycle q3 weeks)

Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy

External beam RADIATION

60 - 66 Gy in 2 Gy fractions for patients without gross disease and 70 Gy for patients with early recurrence) with concurrent cisplatin (40 mg/m2 once weekly)

Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 on the day of signing of the consent form
• ECOG 0-1
• Able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy placed
• Squamous cell carcinoma of the head and neck (excluding lip) \*
• o Eligible primary tumor sites will include the maxillary sinus, oral cavity, HPV-negative oropharynx, larynx, and hypopharynx.
• Gross total resection of known disease at the time of surgery within 10 weeks of registration. All efforts will be made to begin treatment within 6 weeks of surgery.
• At least one of the following criteria
• Close surgical margin (\<5mm) AND ≥2 additional intermediate risk factors (T3 or T4, multiple lymph nodes, LVI, PNI)
• Positive margins not eligible for re-resection (defined as \<1mm)
• Extranodal extension
• Evidence of early gross recurrence on radiation planning scans after definitive intent surgical resection Patients with evidence of gross locoregional disease at the time of radiation are strongly advised to have biopsy confirmation. This requirement may be waived by the PI or the co-PIs. If a biopsy is not performed, patients must meet one of the other entry criteria (close surgical margin and 2 or more additional intermediate risk factors; positive margins not eligible for re-resection; extranodal extension).
• Adequate hematologic, renal, and hepatic function as indicated by:
• Absolute neutrophil count ≥ 1 500 cells/μL
• Platelets ≥ 100 000 cells/μL
• Hemoglobin ≥ 9.0 g/dL (blood transfusions during screening are permitted)

You may not qualify if:

• Metastatic disease
• Prior head and neck radiation
• Peripheral Neuropathy ≥ grade 2
• Hearing Impairment ≥ grade 2
• On-going wound infection, fistula, flap failure
• Use within 14 days prior to randomization or requirement for ongoing treatment with any drug(s) on the prohibited medication list (see below).
• Known history of infection with HIV. If unknown history of HIV, an HIV screening test is to be performed and subjects with positive serology for HIV-1/2 must be excluded.
• Known chronically active HBV or HCV infection. If unknown status, the following tests are to be performed and subjects with positive serology must be excluded:
• HBV screening tests: both HBV sAg and Anti-HepB core IgG.
• HCV screening tests: both HCV-antibody and positive viral load HCV-RNA by PCR.
• Other infections (viral and/or bacterial and/or mycotic) requiring systemic treatment.
• Live-attenuated vaccinations within 30 days prior to first investigational treatment administration.
• Ongoing uncontrolled infection requiring intravenous antibiotic therapy within 1 week prior to randomization.
• Documented weight loss of \>10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin \<3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization.
• Active uncontrolled inflammatory disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, severe extensive psoriasis, and other autoimmune diseases) requiring ongoing treatment with anti-TNF medication.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yao Yu, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single arm phase II.

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: November 24, 2023
• Study Start: November 16, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (7)