What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, such as radiation therapy and enzyme inhibition, have several known side effects. Radiation therapy can cause mucositis, xerostomia, dysphagia, and skin reactions like erythema and desquamation. Severe late toxicities may include fibrosis, soft tissue necrosis, and osteonecrosis. Enzyme inhibitors like Tolinapant may lead to side effects such as gastrointestinal disturbances, fatigue, and potential hematologic toxicities. Combining these treatments can enhance the therapeutic effect but may also increase the incidence and severity of side effects.

What prior FDA approvals exist?

FDA-approved treatments for head and neck cancers have included various approaches such as chemotherapy, targeted therapy, and immunotherapy. For example, cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has been approved for use in combination with radiation therapy for locally or regionally advanced head and neck cancer. Additionally, pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has been approved for recurrent or metastatic head and neck squamous cell carcinoma. While specific enzyme inhibitors like tolinapant are still under investigation, these approvals highlight the diverse strategies employed in treating head and neck cancers, often in combination with radiation therapy.

What other types of research exist?

Promising novel alternatives for head and neck cancer treatment include immune checkpoint inhibitors like pembrolizumab and nivolumab, which have shown efficacy in various cancers including head and neck cancers. Additionally, targeted therapies such as cetuximab, an EGFR inhibitor, and novel agents like durvalumab and tremelimumab are being explored. These therapies offer different mechanisms of action compared to enzyme inhibition and radiation, potentially providing new avenues for treatment.

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Tolinapant + Radiation for Head and Neck Cancer

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

The most common treatments for Head and Neck Cancers include enzyme inhibition and radiation therapy. Enzyme inhibitors, like Tolinapant, block specific enzymes necessary for cancer cell growth and survival, leading to cancer cell death. Radiation therapy uses high-energy x-rays to damage the DNA of cancer cells, preventing them from replicating and causing them to die. These treatments are crucial for patients as they directly target cancer cells, aiming to reduce tumor size and prevent further spread, while preserving normal tissue and function.

Phase < 1

Recruiting

Led By Nicole C Schmitt, MD

Research Sponsored by Emory University

Eligibility Criteria Checklist

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

Must have

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

ECOG performance status ≤1

Must not have

Prior radiotherapy to the head and neck region

Significant cardiovascular disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, tolinapant, combined with radiation therapy for head and neck cancer patients who can't use the standard treatment. Tolinapant may block enzymes that help cancer grow, while radiation kills cancer cells.

Who is the study for?

Adults with previously untreated, locally advanced head and neck cancer who cannot receive cisplatin. They must be in good physical condition (ECOG ≤1), have acceptable organ function, no severe hearing loss or neuropathy, and not be pregnant or breastfeeding. Participants need to use effective contraception and cannot have a history of significant mental illness or substance abuse.

What is being tested?

The trial is testing the combination of a new drug called Tolinapant with radiation therapy against head and neck cancers that can't be treated with cisplatin. The goal is to see if this combo is safe and more effective at killing cancer cells than standard treatments.

What are the potential side effects?

Potential side effects include typical reactions from radiation like skin irritation, fatigue, dry mouth/throat issues, as well as possible effects from Tolinapant such as nausea, vomiting, diarrhea, blood count changes which could increase infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I have a confirmed diagnosis of head and neck cancer that hasn't been treated yet, and I can't receive cisplatin with my radiation.

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I am fully active and can carry on all my pre-disease activities without restriction.

Exclusion Criteria

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

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I have had radiation therapy to my head or neck.

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I have a serious heart condition.

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I have been diagnosed with HIV, HBV, or HCV.

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I have severe nerve damage.

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My cancer has spread to distant parts of my body.

Select...

I am not taking any medications that affect my heart's rhythm.

Select...

I cannot undergo radiotherapy due to health reasons.

Select...

I do not have any uncontrolled illnesses.

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I had a transplant from another person and experienced severe graft-versus-host disease.

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I am currently receiving treatment for another type of cancer.

Select...

I am taking more than 20 mg of corticosteroids daily.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Feasibility of Tolinapant + Radiation (number of patients able to complete treatment)

Safety of Tolinapant + Radiation (number of patients with adverse events per CTCAE v5.0)

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: Treatment (tolinapant, radiation therapy)Experimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Radiation Therapy

2017

Completed Phase 3

~7250

0 / 13Eligibility 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

The most common treatments for Head and Neck Cancers include enzyme inhibition and radiation therapy. Enzyme inhibitors, like Tolinapant, block specific enzymes necessary for cancer cell growth and survival, leading to cancer cell death. Radiation therapy uses high-energy x-rays to damage the DNA of cancer cells, preventing them from replicating and causing them to die. These treatments are crucial for patients as they directly target cancer cells, aiming to reduce tumor size and prevent further spread, while preserving normal tissue and function.