What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, such as chemoradiation, often cause side effects including mucositis, xerostomia, dysphagia, fatigue, nausea, and skin reactions. Cisplatin, frequently used in these regimens, can lead to nephrotoxicity, ototoxicity, and myelosuppression. Radiation therapy may also result in long-term effects like fibrosis, dental issues, and hypothyroidism. Xevinapant, which enhances chemoradiation by promoting cancer cell death, is being studied for its specific side effect profile.

What prior FDA approvals exist?

FDA-approved treatments for head and neck cancers that enhance chemoradiation effectiveness include cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, which has been shown to improve survival when combined with radiation therapy. Additionally, pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has been approved for recurrent or metastatic head and neck squamous cell carcinoma, often in combination with chemotherapy. These treatments, like Xevinapant, aim to improve the efficacy of standard therapies by promoting cancer cell death.

What other types of research exist?

Promising novel alternatives to Xevinapant for head and neck cancer patients include: 1) p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination, which has shown anti-tumor activity and a favorable therapeutic index in phase I trials. 2) Tolinapant (ASTX660), an antagonist of cellular inhibitor of apoptosis proteins, which has demonstrated clinical activity in T-cell lymphoma and is being evaluated in phase 2 studies. 3) Linifanib (ABT-869) combined with veliparib (ABT-888), which has shown enhanced cytotoxicity in head and neck carcinoma cells. 4) Novel C-terminal Hsp90 inhibitors, which have shown improved toxicity profiles and efficacy in preclinical models of head and neck squamous cell cancer.

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Xevinapant + Cisplatin and Radiation for Head and Neck Cancer

Phase 2

Waitlist Available

Led By Yao Yu, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Squamous cell carcinoma of the head and neck (excluding lip) from eligible primary tumor sites including the maxillary sinus, oral cavity, HPV-negative oropharynx, larynx, and hypopharynx

Age ≥ 18 on the day of signing of the consent form

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if adding Xevinapant to the usual post-surgery treatment can help people with high-risk head and neck cancers. Xevinapant aims to make cancer cells more sensitive to treatment by blocking proteins that help them survive.

Who is the study for?

Adults over 18 with high-risk head and neck cancers, who've had surgery, can swallow or have a feeding tube. They should be in good physical condition (ECOG 0-1), not pregnant or breastfeeding, willing to use contraception, and have no early cancer recurrence. Excluded are those with positive margins that can't be re-operated on.

What is being tested?

The trial is testing if adding Xevinapant to the usual chemoradiation therapy after surgery helps people with high-risk head and neck cancers more than the standard treatment alone.

What are the potential side effects?

Possible side effects include typical reactions from chemotherapy like nausea, fatigue, hair loss; radiation therapy may cause skin irritation or difficulty swallowing; specific side effects of Xevinapant are not listed but could resemble other cancer drugs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is a type of squamous cell carcinoma in the head or neck, but not the lip.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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I can swallow liquids or have a working feeding tube.

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I had surgery to remove all visible cancer within the last 10 weeks and am ready to start treatment within 6 weeks of surgery.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression Free Survival

Secondary study objectives

Overall survival

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Xevinapant in Combination with Post-Operative Cisplatin and RadiotherapyExperimental Treatment3 Interventions

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)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cisplatin

2013

Completed Phase 3

~3120

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Head and Neck Cancers include chemoradiation and targeted therapies. Chemoradiation combines chemotherapy and radiation therapy to enhance the effectiveness of both treatments. Chemotherapy drugs like cisplatin damage the DNA of cancer cells, making them more susceptible to radiation, which further damages the DNA and inhibits cell division. Targeted therapies, such as Xevinapant, inhibit specific proteins that prevent cancer cell death, thereby promoting apoptosis and enhancing the effectiveness of chemoradiation. These mechanisms are crucial for patients as they increase the likelihood of destroying cancer cells, reducing tumor size, and improving survival rates.

Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma.In vitro effect of radiation, antibody to epidermal growth factor receptor and Docetaxel in human head and neck squamous carcinoma cells with mutant P53 and over-expressed EGFR.