Xevinapant + Chemoradiation for Head and Neck Cancer

Overseen By Clinical Trials Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Prohibited medications

Disqualifiers: Metastatic disease, Unknown primary, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose of a new drug, xevinapant, when combined with chemotherapy and radiation for treating head and neck cancer. Participants will assist researchers in identifying the optimal amount of xevinapant for future studies. Individuals who have not undergone previous chemotherapy for this cancer and have a form of head and neck cancer that cannot be surgically removed may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients taking prohibited medications or those requiring close monitoring are excluded, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that xevinapant, when combined with chemoradiotherapy (a treatment combining chemotherapy and radiation), may help treat head and neck cancer. Studies have found that xevinapant can be safely used with chemoradiotherapy, with some patients experiencing mild to moderate side effects such as nausea, tiredness, or skin reactions, which are common in cancer treatments.

The safety of xevinapant has been tested in other studies for similar cancers. Although these studies were at different stages, they provide helpful information. In one study, patients handled xevinapant well when used with standard cancer treatments. However, since this trial is in its early stages, it focuses on finding the safest dose. Participants are closely monitored for any side effects to ensure the treatment is as safe as possible.

It is important to remember that everyone reacts differently to treatment. While xevinapant has been well-tolerated in other studies, individual experiences can vary. Participants will be watched carefully to manage any side effects that occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Xevinapant with chemoradiation for head and neck cancer because it offers a novel approach that could enhance treatment effectiveness. Xevinapant is an inhibitor of Inhibitor of Apoptosis Proteins (IAPs), which are proteins that often help cancer cells survive. By targeting IAPs, Xevinapant works differently from standard treatments like cisplatin-based chemoradiation, potentially making cancer cells more susceptible to treatment. Additionally, Xevinapant is administered in cycles alongside carboplatin and paclitaxel, which could optimize its impact and improve patient outcomes. This innovative approach has the potential to improve survival rates and quality of life for patients battling this challenging condition.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that adding xevinapant to a chemotherapy and radiation treatment plan can significantly improve outcomes for people with head and neck cancer. In this trial, participants will receive varying doses of xevinapant alongside chemotherapy with carboplatin and paclitaxel, as well as radiation therapy. One study found that individuals who received xevinapant with their treatment were almost twice as likely to be alive after five years compared to those who did not receive xevinapant (53% vs 28%). This combination treatment enhances the sensitivity of cancer cells to radiation and chemotherapy, potentially leading to better survival rates. These findings suggest that xevinapant could be a promising addition to standard cancer treatments, offering hope for longer survival in patients with this type of cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with certain types of head and neck squamous cell carcinoma who cannot use cisplatin. They must have a specific stage of cancer, measurable disease, good organ function, and agree to contraception. Excluded are those with distant metastasis, prior chemo or radiotherapy for the same cancer within 3 years, severe health issues like recent heart attacks or active infections, pregnant women, and those on certain medications.

Inclusion Criteria

Hemoglobin >= 9.0 g/dL

Total bilirubin <= 1.5 x upper limit of normal (ULN) (except patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL)

Absolute neutrophil count (ANC) >= 1,500 cells/mm3

Exclusion Criteria

I have not received any live vaccines in the last 28 days.

I've had radiation in the same area as my current cancer.

I have had a heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive up to 4 doses of xevinapant to determine the maximum safe dose in combination with chemotherapy and radiation

9 weeks

Weekly visits for 3 cycles

Dose Expansion

Participants receive the best safe dose of xevinapant determined during escalation, in combination with chemotherapy and radiation

9 weeks

Weekly visits for 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Radiation Therapy
• Xevinapant

Trial Overview The study tests different doses of Xevinapant combined with chemotherapy (Paclitaxel and Carboplatin) and radiation therapy in patients with head and neck cancer. It aims to find the maximum safe dose for future phase 2 trials. Participants will undergo treatment cycles lasting three weeks each for a total of three cycles.

How Is the Trial Designed?

Group I: Escalation Group Dose Level 2 Experimental Treatment 4 Interventions

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.

Group II: Escalation Group Dose Level 1 Experimental Treatment 4 Interventions

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.

Group III: Escalation Group Dose Level 0 Experimental Treatment 4 Interventions

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.

Group IV: Escalation Group Dose Level -1 Experimental Treatment 4 Interventions

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.

Group V: Dose Expansion Experimental Treatment 4 Interventions

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.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

EMD Serono

Industry Sponsor

Trials

147

Recruited

27,800+

Dr. Shepard

EMD Serono

Chief Medical Officer since 2021

MD from University of Cincinnati Medical School, Fellowships in Hematology and Oncology at University of Chicago Hospitals and Clinics

Miguel Fernández Alcalde

EMD Serono

Chief Executive Officer

Bachelor's Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master's Degree in Management from IESE Business School

Published Research Related to This Trial

In a phase II trial involving 25 patients with advanced head and neck cancer, carboplatin demonstrated clinical activity, with 24% of patients achieving an objective response, including two complete responses.

The drug was generally well-tolerated, with mild side effects such as nausea, vomiting, and myelosuppression, and no significant renal or neurologic toxicity reported, suggesting it may be a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin, an active drug in advanced head and neck cancer. de Andres Basauri, L., Lopez Pousa, A., Alba, E., et al.[2013]

The combination of paclitaxel, carboplatin, and external beam radiotherapy resulted in a high overall clinical response rate of 91% in 43 patients with advanced head and neck cancer, with 65% achieving a complete response.

Despite the promising efficacy, the treatment caused severe mucositis in 90% of patients, leading to hospitalization for 31%, highlighting significant toxicity concerns associated with this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with weekly paclitaxel and carboplatin for locally advanced head and neck cancer: Long-term follow-up of a Brown University Oncology Group Phase II Study (HN-53). Chougule, PB., Akhtar, MS., Rathore, R., et al.[2015]

In a study of 49 patients with recurrent or metastatic head and neck cancer, the combination of paclitaxel and carboplatin showed a 57% overall response rate in patients with nasopharyngeal cancer, indicating significant efficacy for this specific type of cancer.

The treatment was generally well tolerated, with only low rates of severe toxicities, suggesting it can be safely administered as an outpatient therapy, although its effectiveness was only moderate in non-nasopharyngeal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel by three-hour infusion and carboplatin in advanced carcinoma of nasopharynx and other sites of the head and neck. A phase II study conducted by the Hellenic Cooperative Oncology Group. Fountzilas, G., Skarlos, D., Athanassiades, A., et al.[2022]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a study of 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., et al.[2018]

In a study of 25 patients with locally advanced squamous cell carcinoma of the head and neck who were ineligible for cisplatin, concurrent treatment with carboplatin and radiotherapy resulted in a 70% complete response rate and a median progression-free survival of 42.7 months.

The treatment was generally well-tolerated, with significant toxicities including oral mucositis (56%) and thrombocytopenia (34%), suggesting that carboplatin could be a viable alternative for patients unable to receive cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of concurrent carboplatin plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin. Hamauchi, S., Yokota, T., Onozawa, Y., et al.[2018]

In a phase I trial involving 33 patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin demonstrated a 54% overall response rate, with 27% achieving complete responses, indicating significant efficacy in treating this patient population.

The maximum tolerated dose of paclitaxel was determined to be between 230 and 265 mg/m2, with manageable side effects, primarily grade 3/4 neutropenia and thrombocytopenia, suggesting that this treatment can be safely administered while potentially enhancing organ preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. Dunphy, F., Boyd, J., Dunleavy, T.[2015]

Higher T and N stages in head and neck cancer are associated with lower rates of complete local control and survival, highlighting the need for improved treatment strategies.

Combined-modality treatments, such as induction chemotherapy followed by radiotherapy, show promise in enhancing survival and preserving organ function compared to aggressive surgery or radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modalities in the treatment of head and neck cancers. Aisner, J., Hiponia, D., Conley, B., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37439181/

Long-term results from a clinical study of xevinapant plus ... The results showed that people with this type of cancer who were treated with xevinapant plus chemoradiotherapy were less likely to die, lived longer on ...

2. emdserono.com emdserono.com/us-en/company/news/press-releases/esmo-2022-xevinapant-five-year-data-07-09-2022.html

2022-09-07 ESMO 2022 xevinapant Five Year Data Patients treated with xevinapant plus CRT almost twice as likely to be alive at five years (53% vs 28%) in Phase II study.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00272

Xevinapant or Placebo Plus Platinum-Based ... This study evaluated xevinapant plus chemoradiotherapy (CRT) versus matched placebo plus CRT for unresected locally advanced squamous cell ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04459715

NCT04459715 | A Study of Xevinapant (Debio 1143) in ... The primary objective of the study was to demonstrate superior efficacy of Xevinapant (Debio 1143) vs placebo when added to chemoradiotherapy (CRT) in locally ...

5. ejcancer.com ejcancer.com/article/S0959-8049(22)01817-2/fulltext

Extended follow-up of a phase 2 trial of xevinapant plus ... A phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial

6. merckgroup.com merckgroup.com/en/news/xevinapant-update.html

Merck Provides Update on Xevinapant Program in Locally ... Merck, a leading science and technology company, today announced the discontinuation of the Phase III randomized TrilynX study evaluating xevinapant plus ...

7. debiopharm.com debiopharm.com/wp-content/uploads/2020/09/2020-Debiopharm-xevinapant-ESMO-Debio1143-106.pdf

Safety and efficacy of Xevinapant (Debio 1143), an ... squamous cell carcinoma of the head and neck, gastro-intestinal and gynecological cancer ... Debio 1143 in patients with resectable squamous cell carcinoma of the.