A Randomized, Double-blind, Placebo-controlled, 2-arm Phase III Study to Assess Efficacy and Safety of Xevinapant and Radiotherapy Compared to Placebo and Radiotherapy for Demonstrating Improvement of Disease-free Survival in Participants With Resected Squamous Cell Carcinoma of the Head and Neck, Who Are at High Risk for Relapse and Are Ineligible for High-dose Cisplatin (XRAY VISION)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 166
- 试验地点
- 206
- 主要终点
- Disease-Free Survival (DFS)
研究概览
简要总结
The purpose of this study is to demonstrate the superior efficacy of Xevinapant (Debio 1143) versus placebo when added to radiotherapy in the treatment of high-risk participants with resected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) who are ineligible to receive cisplatin-based chemoradiation concurrently. Study details include: Study duration: Participants will be followed until the last on-study participant reaches his/her 60-month post-randomization visit, a decision to end the study has been triggered, or until premature discontinuation from study, whichever occurs first. Treatment duration: 18 weeks, consisting of six 3-week cycles. Health measurement/observation: Improved Disease-Free Survival. Visit frequency: Weekly visit during combination therapy period, once every 3 weeks during monotherapy period, and every 3, 4, or 6 months during the Disease-Free Survival Follow-up period in Year 1, 2 and 3, or 4 and 5 (with telephone contact in between), respectively, and every 3 months (telephone visits allowed) during the Overall Survival Follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 and able to tolerate standard of care IMRT treatment according to Investigator assessment
- •Participants with histologically confirmed squamous cell carcinoma with one of the following primary sites: oral cavity, oropharynx, hypopharynx or larynx. Participants have received surgery with curative intent on these sites in the past 4 to 10 weeks before start of treatment (Cycle 1 Day 1)
- •Oropharynx (OPC) participants must have known human papillomavirus (HPV) status as determined by p16 expression using immunohistochemistry (ICH)
- •Participants with no residual disease by computed tomography (CT) or magnetic resonance imaging (MRI) and have a high risk of relapse with 1 or 2 of the following criteria, confirmed by local histopathology: • nodal extra-capsular extension (ECE) and positive resection margins (R1 or close margin less than or equal to (<=) 1 millimeter (mm)
- •Are unfit to receive high-dose cisplatin by meeting one or more of the following criteria: estimated glomerular filtration rate (eGFR) < 60 milliliter per minute per 1.73 meter square (mL/min /1.73 m^2); History of hearing impairment, defined as Grade >= 2 audiometric hearing loss or tinnitus Grade >=
- •An audiogram is not required if one of the other criteria meets unfitness to receive high-dose cisplatin; Peripheral neuropathy > = Grade 2 and if >= 70 years, unfit according to G8 questionnaire (Score <= 14) or ineligible for cisplatin treatment due to age limit according to national guidelines
- •Participants with adequate renal, hematologic and hepatic function as defined in the protocol
- •Other protocol-defined inclusion criteria could apply
排除标准
- •Any condition, including any uncontrolled disease state other than SCCHN that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
- •Participants with incomplete surgery
- •Participants with recurrent or metastatic disease
- •Primary tumor of nasopharyngeal, paranasal sinuses, nasal cavity, salivary, thyroid or parathyroid gland, skin or unknown primary site
- •Prior definitive, neoadjuvant, concurrent or adjuvant (C)RT to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents
- •Participation in any interventional clinical study within 28 days prior to screening or during participation in this study
- •Known contraindication to undergoing positron emission tomography with 18F-FDG-PET-CT scans, or both contrast-enhanced MRI and contrast-enhanced CT scans
- •Known allergy to Xevinapant (Debio 1143) or any excipient known to be present in Xevinapant (Debio 1143) or in the placebo formulation
- •Other protocol-defined exclusion criteria could apply
研究组 & 干预措施
Xevinapant + IMRT
Participants received 3 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 66 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).
干预措施: Xevinapant (Drug)
Xevinapant + IMRT
Participants received 3 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 66 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).
干预措施: IMRT (Radiation)
Placebo + IMRT
Participants received 3 cycles of oral solution of placebo matched to Xevinapant (Debio 1143) once daily from Day 1 to 14 per 3-week cycle in combination with with 66 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week followed by 3 cycles of monotherapy of placebo matched to Xevinapant (Debio 1143) from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).
干预措施: IMRT (Radiation)
Placebo + IMRT
Participants received 3 cycles of oral solution of placebo matched to Xevinapant (Debio 1143) once daily from Day 1 to 14 per 3-week cycle in combination with with 66 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 33 fractions, 2 Gy/fraction, 5 days/week followed by 3 cycles of monotherapy of placebo matched to Xevinapant (Debio 1143) from Day 1 to 14, per 3-week cycle (Each cycle is of 3 weeks).
干预措施: Placebo (Drug)
结局指标
主要结局
Disease-Free Survival (DFS)
时间窗: Time from randomization to the first occurrence of death from any cause or objective disease recurrence, assessed up to 22.7 months
DFS defined as the time from randomization to the first occurrence of any of the following events: Death from any cause; Objective Disease Recurrence (earlier date of first imaging or biopsy collection confirming event at a DFS assessment): Local or regional relapse which is subsequently confirmed by histopathology unless medically contraindicated or medical risk of biopsy deemed too high: Distant metastases. Confirmation of pathology is recommended in case of solitary metastasis (especially in the lung) after considering potential contraindication and/or medical risk associated with biopsy. DFS time was estimated according to Kaplan-Meier method.
次要结局
- Overall Survival (OS)(Time from randomization to death from any cause, assessed up to 22.7 months)
- Time to Subsequent Cancer Treatments(Time from randomization to the start of first subsequent cancer treatment, assessed up to 22.7 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-related TEAEs(Time from randomization up to 22.7 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-HN35) Score(Baseline, Day 64 and End of treatment (Day 134))
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Score(Baseline, Day 64 and End of treatment (Day 134))
- Change From Baseline in EuroQOL 5 Dimension 5 Level Health-Related Quality of Life Measure Visual Analog Scale Score (EQ-5D-5L VAS)(Baseline, Day 64 and End of treatment (Day 134))