A Phase II Randomized Controlled Clinical Trial of Rimegepant-Sensitized Neoadjuvant Chemoimmunotherapy in Patients With Oral/Oropharyngeal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Major Pathological Response Rate
研究概览
简要总结
This study will evaluate whether adding rimegepant to standard neoadjuvant chemoimmunotherapy can improve treatment response in patients with primary or recurrent oral or oropharyngeal squamous cell carcinoma who are planned to undergo surgery.
Rimegepant blocks the receptor for calcitonin gene-related peptide, also known as CGRP. CGRP signaling may affect the tumor immune environment and the response of tumors to anticancer treatment.
The study includes an initial safety run-in stage involving 20 participants, followed by a randomized controlled stage involving 200 participants. During the randomized stage, participants will be assigned in a 1:1 ratio to receive standard neoadjuvant chemoimmunotherapy either with or without rimegepant. All participants will receive two cycles of neoadjuvant treatment followed by definitive or intended curative surgery.
The main outcome is the major pathological response rate, defined as 10% or less residual viable tumor in the surgical specimen. Other outcomes include pathological complete response, objective response, event-free survival, overall survival, changes in pain and quality of life, and treatment safety.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years, regardless of sex.
- •Histologically or cytologically confirmed oral or oropharyngeal squamous cell carcinoma, including primary disease or recurrent disease after previous treatment that is considered amenable to repeat curative-intent resection.
- •Planned to receive neoadjuvant chemoimmunotherapy followed by surgery after multidisciplinary evaluation.
- •At least one evaluable lesion according to Response Evaluation Criteria in Solid Tumors version 1.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Adequate major organ function.
- •Voluntary participation and provision of written informed consent.
排除标准
- •Severe cardiac, hepatic, or renal dysfunction.
- •Active autoimmune disease.
- •Pregnancy or breastfeeding.
- •Known allergy or hypersensitivity to rimegepant or any component of the planned neoadjuvant treatment.
- •Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.
研究组 & 干预措施
Safety Run-In Combination Arm
Twenty participants will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery. Safety and tolerability will be evaluated before initiation of the randomized stage.
干预措施: Tislelizumab (Drug)
Safety Run-In Combination Arm
Twenty participants will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery. Safety and tolerability will be evaluated before initiation of the randomized stage.
干预措施: Nab-paclitaxel (Drug)
Safety Run-In Combination Arm
Twenty participants will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery. Safety and tolerability will be evaluated before initiation of the randomized stage.
干预措施: Rimegepant (Drug)
Randomized Combination Arm
Participants randomized to this arm will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Cisplatin (Drug)
Randomized Combination Arm
Participants randomized to this arm will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Tislelizumab (Drug)
Randomized Control Arm
Participants randomized to this arm will receive standard neoadjuvant chemoimmunotherapy alone for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Cisplatin (Drug)
Safety Run-In Combination Arm
Twenty participants will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery. Safety and tolerability will be evaluated before initiation of the randomized stage.
干预措施: Cisplatin (Drug)
Randomized Control Arm
Participants randomized to this arm will receive standard neoadjuvant chemoimmunotherapy alone for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Nab-paclitaxel (Drug)
Randomized Combination Arm
Participants randomized to this arm will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Rimegepant (Drug)
Randomized Control Arm
Participants randomized to this arm will receive standard neoadjuvant chemoimmunotherapy alone for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Tislelizumab (Drug)
Randomized Combination Arm
Participants randomized to this arm will receive rimegepant plus standard neoadjuvant chemoimmunotherapy for two 3-week cycles, followed by definitive or intended curative surgery.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Major Pathological Response Rate
时间窗: At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment
Percentage of participants with 10% or less residual viable tumor cells in the resected primary or recurrent tumor specimen after neoadjuvant treatment. For the randomized efficacy analysis, participants who do not undergo surgery or whose surgical specimens are not evaluable for pathological response will be considered not to have achieved major pathological response. Results will also be reported separately for participants with primary and recurrent disease.
次要结局
- Pathological Complete Response Rate(At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment)
- Objective Response Rate(From baseline to preoperative radiographic assessment after completion of two 3-week cycles of neoadjuvant treatment)
- Event-Free Survival(From randomization to the first event or censoring, assessed up to 5 years)
- Overall Survival(From randomization until death or censoring, assessed up to 5 years)
- Change From Baseline in Pain Score(At baseline, at the end of each neoadjuvant treatment cycle, and at the preoperative assessment)
- Change From Baseline in Quality of Life(At baseline, at the end of each neoadjuvant treatment cycle, and at the preoperative assessment)
- Incidence of Treatment-Emergent Adverse Events(From signing informed consent through 90 days after the last dose of study treatment)