Xevinapant + Cisplatin and Radiation for Head and Neck Cancer

Not currently recruiting at 6 trial locations

Overseen By Nancy Lee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anti-TNF, QT prolonging

Disqualifiers: Metastatic disease, HIV, HBV, HCV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding Xevinapant to the usual chemoradiation treatment after surgery can more effectively treat high-risk head and neck cancers. Participants will receive a combination of Xevinapant, cisplatin (a chemotherapy drug), and radiation therapy to potentially improve outcomes. Suitable candidates have undergone surgery for specific types of head and neck cancer, such as in the oral cavity or larynx, and face high risks of recurrence. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any medications on the prohibited list within 14 days before starting the trial. If you are on any medication that prolongs the QT interval, it must be discontinued or replaced with a safe alternative 7 days before starting treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that xevinapant, when combined with standard chemoradiotherapy, has produced mixed safety results. Some studies found that xevinapant was generally well-tolerated and helped prevent cancer recurrence. However, other research raised safety concerns, indicating it did not improve survival rates and caused negative effects compared to a placebo.

Cisplatin, a chemotherapy drug, is well-known and commonly used for head and neck cancers. Its long history of use has provided a well-understood safety profile.

In summary, while cisplatin is a familiar treatment, the safety of xevinapant remains uncertain, with some studies highlighting potential issues. Prospective participants should discuss these findings with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about xevinapant in combination with cisplatin and radiation for head and neck cancer because it adds a new dimension to existing therapies. Unlike the standard treatments, which typically involve just cisplatin and radiation, xevinapant introduces a novel mechanism by inhibiting apoptosis proteins, potentially making cancer cells more susceptible to treatment. This approach may enhance the effectiveness of the standard chemoradiation regimen, offering hope for improved outcomes in patients. By integrating xevinapant, there's potential to not only boost the efficacy of the treatment but also to offer a new strategy that might reduce the recurrence of cancer.

What evidence suggests that Xevinapant in combination with Cisplatin and Radiation could be an effective treatment for head and neck cancer?

In this trial, participants will receive Xevinapant combined with post-operative Cisplatin and radiotherapy. Research has shown that adding Xevinapant to standard chemoradiotherapy (CRT) can significantly improve outcomes for people with advanced head and neck cancer. Studies have found that patients receiving Xevinapant with CRT live longer overall compared to those not receiving Xevinapant. Specifically, long-term results indicate that Xevinapant enhances CRT's ability to prevent cancer recurrence. Additionally, patients treated with Xevinapant tend to live longer and have a lower risk of cancer-related death. These findings suggest that Xevinapant could be a valuable addition to standard treatments for head and neck cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Yao Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My cancer surgery had narrow margins or showed signs of spreading, and I can't have more surgery to remove it.

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

I am fully active or can carry out light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Chemoradiation

Participants receive concurrent radiation, cisplatin, and xevinapant

6-9 weeks

Weekly visits for treatment

Adjuvant Phase

Participants receive additional cycles of xevinapant

9 weeks

Every 3 weeks for 3 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• External beam
• Xevinapant

Trial Overview 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.

How Is the Trial Designed?

Group I: Xevinapant in Combination with Post-Operative Cisplatin and Radiotherapy Experimental Treatment 3 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)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study of 72 patients with advanced head and neck cancer receiving concurrent chemoradiotherapy with generic cisplatin, treatment completion rates were high, indicating good tolerability of the drug.

The incidence of severe adverse events was relatively low, with only 14% experiencing grade 3/4 leukopenia and no severe kidney issues reported, suggesting that generic cisplatin is a safe option for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy With Generic Cisplatin Formulations for Head and Neck Cancers. Shimada, R., Tsukahara, K., Takase, S., et al.[2020]

In a study involving 17 patients with head and neck squamous cell carcinoma, treatment with cis-diamminedichloroplatinum (CDDP) at a dose of 2.5 mg/kg resulted in one complete response and five partial responses, indicating its potential efficacy as a treatment.

The treatment was associated with only moderate toxicity, suggesting that CDDP may be a relatively safe option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-disamminedichloroplatinum (II) CDDP: single agent in the treatment of advanced head and neck squamous cell carcinoma. Tranter, RM., Howell, A.[2019]

Cisplatin, when used as a radiosensitizer in conjunction with radiation therapy for advanced squamous cell carcinoma of the head and neck, has shown to significantly improve treatment outcomes, including higher response rates and prolonged survival.

The mechanism of action for cisplatin's effectiveness includes its ability to enhance DNA damage in tumor cells and inhibit their repair, which leads to better control of the disease when combined with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of advanced squamous cell carcinoma of the head and neck with cisplatin during concomitant radiation therapy. Sharma, VM., Wilson, WR.[2019]

In a pilot study involving three patients with advanced head and neck cancer, the combination of radiation therapy and cisplatin (CDDP) resulted in severe side effects, including abscesses and significant nausea and vomiting.

The observed toxicities were greater than expected from either treatment alone, raising concerns about the safety of using this combination in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. Creagan, ET., Fountain, KS., Frytak, S., et al.[2019]

The addition of low-dose cisplatin (CDDP) to hyperfractionated radiation therapy (Hfx RT) significantly improved survival rates in patients with locally advanced squamous cell carcinoma of the head and neck, with 68% survival at 2 years compared to 49% with Hfx RT alone.

Despite the survival benefits, the combination treatment did not increase the incidence of severe radiation-induced toxicity compared to Hfx RT alone, although higher rates of hematologic toxicity were observed in patients receiving CDDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. Jeremic, B., Shibamoto, Y., Milicic, B., et al.[2022]

In a study of 181 patients with locally advanced head and neck cancers, nimotuzumab-based concurrent chemoradiotherapy resulted in the least hematological toxicities compared to cisplatin, nedaplatin, and lobaplatin.

Lobaplatin was associated with a higher incidence of severe leukopenia (48.5%) and thrombocytopenia compared to cisplatin, indicating that while some alternatives to cisplatin may reduce gastrointestinal and nephrotoxicity, they can still pose significant hematological risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematological Toxicities of Concurrent Chemoradiotherapies in Head and Neck Cancers: Comparison Among Cisplatin, Nedaplatin, Lobaplatin, and Nimotuzumab. Wu, Q., Zhu, C., Zhang, S., et al.[2022]

Citations

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

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

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 First randomized trial in decades to show significant improvement in overall survival in patients with LA SCCHN.

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922018172

Extended follow-up of a phase 2 trial of xevinapant plus ... In this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival.

5. biomedicine.video biomedicine.video/oncology-hematology/xevinapant-crt-in-la-scchn-extended-follow-up-study

Xevinapant + CRT in LA SCCHN: extended follow-up study Xevinapant combined with CRT showed a well-tolerated safety profile and significantly improved the ability of CRT preventing recurrence of cancer in patients ...

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. targetedonc.com targetedonc.com/view/xevinapant-fails-to-improve-efs-in-patients-with-head-and-neck-cancer

Xevinapant Fails to Improve EFS in Patients with Head ... Xevinapant fails to enhance event-free survival (EFS) in head and neck cancer patients, revealing safety concerns and detrimental effects in ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40902136/

Xevinapant or Placebo Plus Platinum-Based ... Xevinapant plus CRT did not improve EFS (EFS was shorter with xevinapant v placebo) and demonstrated an unfavorable safety profile versus ...