NCT06084845

Testing the Addition of an Investigational Drug, Xevinapant, to Usual Radiation Therapy Plus Cisplatin/Carboplatin for Patients With Head and Neck Cancer

Phase II Trial of Xevinapant and Chemoradiotherapy in Adjuvant Treatment for Patients With Head and Neck Squamous Cell Carcinoma With High Risk Pathologic Features

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: ECOG-ACRIN Cancer Research Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial compares the effect of usual radiation therapy with cisplatin/carboplatin (chemoradiation) to the addition of xevinapant with chemoradiation in patients with head and neck cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Xevinapant is a first-in-class antagonist of inhibitor of apoptosis (programmed cell death) proteins (IAPs), which leads to tumor cell death and enhances tumor cell sensitivity to chemotherapy and radiotherapy. Giving xevinapant with chemoradiation may be more effective in preventing head and neck cancer from growing or spreading than chemoradiation alone.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate whether adding xevinapant to post-operative adjuvant treatment with cisplatin + radiation followed by xevinapant monotherapy in patients with surgically resected head and neck squamous cell carcinoma (HNSCC) who have extra-nodal extension (ENE) and/or positive margins will improve the disease-free survival (DFS). SECONDARY OBJECTIVES: I. To evaluate the following endpoints: Overall Survival (OS), rates of distant metastasis (DM), local regional control (LRR). II. To assess safety and tolerability of treatment intensification. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive cisplatin or carboplatin intravenously (IV) over 30-60 minutes once a week (QW) for 6 doses with concurrent intensity-modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) five days a week for 30-33 fractions in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, and/or chest x-ray during screening and follow-up. Patients may also undergo blood sample collection during follow-up. ARM B: Patients receive cisplatin or carboplatin IV over 30-60 minutes QW for 6 doses with concurrent IMRT and IGRT five days a week for 30-33 fractions in the absence of disease progression or unacceptable toxicity. Patients also receive xevinapant orally (PO) on days 1-14 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, PET-CT, and/or chest x-ray during screening and follow-up. Patients may also undergo blood sample collection during follow-up. Upon completion of study treatment, patients are followed up at 30 days and every 6 months if patient is \< 3 years from randomization and every 12 months if patient is 3-5 years from randomization.

Conditions

• Head and Neck Squamous Cell Carcinoma
• Hypopharyngeal Squamous Cell Carcinoma
• Laryngeal Squamous Cell Carcinoma
• Oral Cavity Squamous Cell Carcinoma
• Oropharyngeal Squamous Cell Carcinoma
• Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
• Stage III Hypopharyngeal Carcinoma AJCC v8
• Stage III Laryngeal Cancer AJCC v8
• Stage III Lip and Oral Cavity Cancer AJCC v8
• Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8
• Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
• Stage IV Hypopharyngeal Carcinoma AJCC v8
• Stage IV Laryngeal Cancer AJCC v8
• Stage IV Lip and Oral Cavity Cancer AJCC v8
• Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Carboplatin	Given IV
PROCEDURE	Chest Radiography	Undergo chest x-ray
DRUG	Cisplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT and/or PET-CT
RADIATION	Image Guided Radiation Therapy	Undergo IGRT
RADIATION	Intensity-Modulated Radiation Therapy	Undergo IMRT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET-CT
DRUG	Xevinapant	Given PO

Timeline

• Start date: 2024-04-12
• Primary completion: 2028-05-31
• Completion: 2028-05-31
• First posted: 2023-10-16
• Last updated: 2024-07-25