Xevinapant + Cisplatin and Radiation for Head and Neck Cancer

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

4 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination of Xevinapant, Cisplatin, and Radiation for head and neck cancer?

Research shows that using cisplatin with radiation therapy can enhance the treatment's ability to control tumors in advanced head and neck cancer. Cisplatin acts as a radiosensitizer, meaning it makes cancer cells more sensitive to radiation, which can lead to better tumor control and longer survival rates. ^{1 2 3 4 5}

Is the combination of Xevinapant, Cisplatin, and Radiation safe for treating head and neck cancer?

Cisplatin, when used with radiation for head and neck cancer, has shown moderate to severe side effects, including nausea, vomiting, and blood-related issues like leukopenia (low white blood cell count) and neutropenia (low neutrophil count). However, some studies suggest that with proper management, such as hydration, these treatments can be well tolerated. ^{4 6 7 8 9}

How does the drug Xevinapant combined with Cisplatin and Radiation differ from other treatments for head and neck cancer?

Xevinapant is a novel drug that, when combined with Cisplatin and radiation, may offer a new approach to treating head and neck cancer by potentially enhancing the effectiveness of the standard treatment. This combination could provide an alternative to the traditional cisplatin-based chemoradiation, which is known for its high toxicity and compliance issues. ^{1 3 4 6 10}

Research Team

Yao Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. United States 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. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

A phase I trial combining oral cisplatin (CP Ethypharm) with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma. [2019]

3. India pubmed.ncbi.nlm.nih.gov

Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hematological Toxicities of Concurrent Chemoradiotherapies in Head and Neck Cancers: Comparison Among Cisplatin, Nedaplatin, Lobaplatin, and Nimotuzumab. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Concomitant radiation therapy and cis-diamminedichloroplatinum (II) in patients with advanced head and neck cancer. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy With Generic Cisplatin Formulations for Head and Neck Cancers. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of mannitol-based reduced-volume hydration on kidney function in concomitant cisplatin-based chemoradiation for head-and-neck squamous cell carcinoma. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Carboplatin/Paclitaxel-Based Radiochemotherapy in Locally Advanced Squamous Cell Carcinoma of Head and Neck. [2019]