What side effects are associated with this type of intervention?

Common treatments for Head and Neck Cancers, particularly those involving radiotherapy and inhibitors of apoptosis proteins like Xevinapant (Debio 1143), often result in side effects such as fatigue, rash, anorexia, diarrhea, lethargy, mucositis, dermatitis, and edema. These side effects are consistent across various combination therapies and highlight the need for careful management of treatment-related toxicities.

What prior FDA approvals exist?

The FDA has approved several treatments for head and neck cancers that enhance the efficacy of radiotherapy. Cetuximab, an EGFR inhibitor, is one such drug that has been used in combination with radiotherapy to improve outcomes in patients with locally advanced head and neck cancer. Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has also been approved for recurrent or metastatic head and neck squamous cell carcinoma, often in combination with chemotherapy. These treatments work by either directly targeting cancer cell pathways or by modulating the immune response to enhance the effects of radiotherapy.

What other types of research exist?

Promising novel alternatives to Xevinapant for Head and Neck Cancer patients include: 1) EGFR tyrosine kinase inhibitors combined with agents like deguelin, which have shown potential in PIK3CA-mutated HNSCC by enhancing apoptosis through inhibition of the AKT pathway. 2) Immunotherapies such as nivolumab and pembrolizumab, which have demonstrated improved recurrence-free survival in high-risk melanoma and may offer similar benefits in HNC. 3) BTK inhibitors like ibrutinib, which have shown efficacy in other cancers and could be explored for HNC. These alternatives should be discussed with a healthcare provider to tailor the best treatment plan.

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Xevinapant + Radiotherapy for Head and Neck Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for Head and Neck Cancers include radiotherapy, chemotherapy, and targeted therapies. Radiotherapy works by damaging the DNA of cancer cells, leading to cell death. Chemotherapy, such as cisplatin, enhances this effect by making cancer cells more susceptible to radiation. Targeted therapies, like Xevinapant (Debio 1143), inhibit proteins that prevent apoptosis (programmed cell death), thereby promoting cancer cell death and enhancing the efficacy of radiotherapy. These mechanisms are crucial for patients as they aim to maximize cancer cell eradication while minimizing damage to surrounding healthy tissues, improving overall treatment outcomes and reducing side effects.

Phase 3

Recruiting

Research Sponsored by EMD Serono Research & Development Institute, Inc.

Eligibility Criteria Checklist

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

Must have

Participants unfit for high-dose cisplatin due to criteria such as eGFR < 60 mL/min/1.73 m^2, history of Grade >= 2 audiometric hearing loss or tinnitus, Grade >= 2 peripheral neuropathy, or G8 questionnaire score <= 14 if >= 70 years

Participants with no residual disease by CT or MRI and high risk of relapse with nodal extra-capsular extension (ECE) and positive resection margins (R1 or close margin <= 1 mm)

Must not have

Participants with incomplete surgery

Participants with recurrent or metastatic disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from randomization until end of study (up to 5 years)

Awards & highlights

Summary

This trial is testing a new cancer treatment against placebo to see if it is more effective in treating people with a certain type of head and neck cancer.

Who is the study for?

This trial is for adults with high-risk, resected head and neck cancer who can't receive cisplatin. They must have had surgery recently, no remaining disease visible on scans, and a risk of relapse. Participants need to be able to handle standard radiotherapy and have good organ function.Check my eligibility

What is being tested?

The study tests if Xevinapant (Debio 1143) improves outcomes when added to radiotherapy compared to placebo in patients ineligible for cisplatin chemotherapy. It's an 18-week treatment followed by regular check-ups for up to five years.See study design

What are the potential side effects?

Possible side effects of Xevinapant include typical reactions related to immune system activation such as fatigue, nausea, skin reactions from radiotherapy, potential liver or kidney issues, and other symptoms that may vary among individuals.

Eligibility Criteria

Inclusion Criteria

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

Select...

I cannot receive high-dose cisplatin due to kidney issues, hearing loss, nerve damage, or frailty.

Select...

My scans show no remaining cancer, but I'm at high risk of it coming back due to certain factors.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My surgery did not remove all of the cancer.

Select...

My cancer has returned or spread to other parts of my body.

Select...

I am not allergic to Xevinapant or its ingredients and can undergo all required scans.

Select...

My cancer did not start in my mouth or throat.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from randomization until end of study (up to 5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from randomization until end of study (up to 5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from randomization until end of study (up to 5 years) for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Disease-Free Survival (DFS)

Secondary outcome measures

Change from Baseline in EuroQOL 5 Dimension 5 Level Health-Related Quality of Life Measure Visual Analog Scale Score (EQ-5D-5L VAS)

Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN35) Score

Change from Baseline in European Organization for research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Score

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Arm A: Xevinapant (Debio 1143) + IMRTExperimental Treatment2 Interventions

Group II: Arm B: Placebo + IMRTPlacebo Group2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

IMRT

2003

Completed Phase 3

~1570

Xevinapant (Debio 1143)

2022

Completed Phase 1

~30

0 / 6Eligibility 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 radiotherapy, chemotherapy, and targeted therapies. Radiotherapy works by damaging the DNA of cancer cells, leading to cell death. Chemotherapy, such as cisplatin, enhances this effect by making cancer cells more susceptible to radiation. Targeted therapies, like Xevinapant (Debio 1143), inhibit proteins that prevent apoptosis (programmed cell death), thereby promoting cancer cell death and enhancing the efficacy of radiotherapy. These mechanisms are crucial for patients as they aim to maximize cancer cell eradication while minimizing damage to surrounding healthy tissues, improving overall treatment outcomes and reducing side effects.

Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma.Bortezomib-induced apoptosis with limited clinical response is accompanied by inhibition of canonical but not alternative nuclear factor-{kappa}B subunits in head and neck cancer.