A Study of Xevinapant (Debio 1143) in Combination With Platinum-Based Chemotherapy and Standard Fractionation Intensity-Modulated Radiotherapy in Participants With Locally Advanced Squamous Cell Carcinoma of the Head and Neck, Suitable for Definitive Chemoradiotherapy (TrilynX)
- Conditions
- Squamous Cell Carcinoma of the Head and Neck
- Interventions
- Radiation: Intensity Modulation Radiation Therapy (IMRT)Drug: Placebo
- Registration Number
- NCT04459715
- Brief Summary
The primary objective of the study is to demonstrate superior efficacy of Xevinapant (Debio 1143) vs placebo when added to chemoradiotherapy (CRT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 730
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
- Histologically confirmed diagnosis of previously untreated Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN) participant (stage III, IVa or IVb according to the American Joint Committee on Cancer(AJCC))/Classification of malignant tumors: T=size of the primary tumor, N=regional lymph node involvement, M=distant metastasis (TNM) Staging System, 8th Edition.) suitable for definitive ChemoRadiotherapy (CRT), of at least one of the following sites: oropharynx, hypopharynx and larynx
- For OroPharyngeal Cancer (OPC) participants, primary tumors must be human papillomavirus (HPV)-negative as determined by p16 expression using immunohistochemistry
- Evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on Response evaluation criteria in solid tumors (RECIST) version 1.1
- Peripheral neuropathy less than (<) grade 2
- Adequate hematologic, renal and hepatic function
- Other protocol defined inclusion criteria may apply
- Primary tumor of nasopharynx, paranasal sinuses, nasal or oral cavity, salivary, thyroid or parathyroid gland pathologies, skin or unknown primary site
- Metastatic disease (stage IVc as per AJCC/TNM, 8th Ed.)
- Prior definitive or adjuvant Radiotherapy (RT) and/or radical surgery to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents
- Documented weight loss of >10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin < 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization
- Known allergy to Xevinapant (Debio 1143), cisplatin, carboplatin, other platinum-based agent or any excipient known to be present in any of these products or in the placebo formulation
- other protocol defined exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Xevinapant (Debio 1143) Xevinapant (Debio 1143) Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Xevinapant (Debio 1143) Monotherapy period (Cycles 4-6): • Xevinapant (Debio 1143) Xevinapant (Debio 1143) Cisplatin Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Xevinapant (Debio 1143) Monotherapy period (Cycles 4-6): • Xevinapant (Debio 1143) Xevinapant (Debio 1143) Intensity Modulation Radiation Therapy (IMRT) Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Xevinapant (Debio 1143) Monotherapy period (Cycles 4-6): • Xevinapant (Debio 1143) Placebo Cisplatin Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Matched placebo Monotherapy period (Cycles 4-6): • Matched placebo Placebo Intensity Modulation Radiation Therapy (IMRT) Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Matched placebo Monotherapy period (Cycles 4-6): • Matched placebo Placebo Placebo Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Matched placebo Monotherapy period (Cycles 4-6): • Matched placebo
- Primary Outcome Measures
Name Time Method Event-Free Survival (EFS) Up to 5 years EFS is the time from the date of randomization to the date of first record of disease progression or death.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to 5 years ORR defined as proportion of participants with complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by Blinded Independent Review Committee (BIRC).
Complete Response Rate (CRR) Up to 5 years CRR defined as proportion of participants with complete response (CR) as assessed by Blinded Independent Review Committee (BIRC).
Overall survival (OS) Up to 5 years OS is the time from randomization to death due to any cause.
Changes from Baseline in Global Health Status/Quality of Life (GHS/QoL) and Fatigue Symptom Prior to the first dose of study treatment (Baseline) and at the time of last follow-up (Up to 5 years) Change from baseline in GHS/QoL and Fatigue Symptom using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30)
Changes from Baseline in Swallowing and Pain Symptoms Prior to the first dose of study treatment (Baseline) and at the time of last follow-up (Up to 5 years) Change from baseline in swallowing, and pain symptoms using the EORTC Head and Neck Questionnaire (EORTC QLQ-H\&N35)
Progression-Free Survival (PFS) Up to 5 years PFS is the time from randomization to the earliest between PFS event or End of Study (EOS)
Locoregional Control (LRC) From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or EOS (Up to 5 years) Duration of Response (DOR) Up to 5 years Duration of response (DoR) defined as the time from the first evidence of response (partial or complete, as assessed by the BIRC according to RECIST v1.1) to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause.
Number of Participants with Radical Salvage Surgery Up to 5 years Time to Subsequent Systemic Cancer Treatments Up to 5 years Safety and Tolerability as assessed by incidence and severity of Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), Changes in Laboratory Values, Vital Signs, Electrocardiogram (ECGs) and Extent of Exposure From signed informed consent to EOS (within 6.8 years)
Trial Locations
- Locations (285)
The University of Alabama at Birmingham - Hazelrig-Salter Radiation Oncology Center (HSROC)
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Regents of the University of California
🇺🇸San Francisco, California, United States
UCSF
🇺🇸San Francisco, California, United States
The Oncology Institute of Hope & Innovation
🇺🇸Whittier, California, United States
University of Colorado at Denver and Health Sciences Center
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
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