Oral Squamous Cell Carcinoma (OSCC), Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Conditions
Keywords
Rimegepant, Neoadjuvant Chemoimmunotherapy, CGRP Receptor Antagonist, Calcitonin Gene-Related Peptide, Major Pathological Response, Tislelizumab, Nab-Paclitaxel, Cisplatin
Brief summary
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.
Interventions
DRUGRimegepant
Rimegepant 75 mg will be administered orally every other day from the initiation until the completion of neoadjuvant chemoimmunotherapy.
DRUGTislelizumab
Tislelizumab 200 mg will be administered by intravenous infusion on Day 1 of each 3-week treatment cycle for two cycles.
DRUGNab-paclitaxel
Nab-paclitaxel 260 mg/m² will be administered by intravenous infusion on Day 2 of each 3-week treatment cycle for two cycles.
DRUGCisplatin
A total dose of cisplatin 75 mg/m² will be administered intravenously over Days 2 and 3 of each 3-week treatment cycle for two cycles.
Sponsors
Shanghai Zhongshan Hospital
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of an initial open-label safety run-in stage followed by an open-label randomized parallel-group stage. The safety run-in stage will enroll 20 participants who will receive rimegepant plus standard neoadjuvant chemoimmunotherapy. After the prespecified safety criteria are met, 200 participants will be randomized in a 1:1 ratio to receive rimegepant plus standard neoadjuvant chemoimmunotherapy or standard neoadjuvant chemoimmunotherapy alone. Stratified block randomization will be used in the randomized stage.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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 1.1. * Eastern Cooperative Oncology Group performance status of 0 or 1. * Adequate major organ function. * Voluntary participation and provision of written informed consent.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response Rate | At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment | Percentage of participants with no residual viable tumor cells in the resected primary or recurrent tumor specimen after neoadjuvant treatment, using the same pathological assessment scope as that used for major pathological response. Participants who do not undergo surgery or whose surgical specimens are not evaluable for pathological response will be considered not to have achieved pathological complete response in the randomized efficacy analysis. |
| Objective Response Rate | From baseline to preoperative radiographic assessment after completion of two 3-week cycles of neoadjuvant treatment | Percentage of participants with a complete response or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1. |
| Event-Free Survival | From randomization to the first event or censoring, assessed up to 5 years | Event-free survival is defined as the time from randomization to the first occurrence of any of the following: disease progression during neoadjuvant treatment that precludes the planned definitive or intended curative surgery; locoregional recurrence or progression after surgery; distant metastasis or distant disease progression; or death from any cause. Participants without an event will be censored at the date of the last assessment confirming that they remained event-free. |
| Overall Survival | From randomization until death or censoring, assessed up to 5 years | Overall survival is defined as the time from randomization to death from any cause. Participants who are alive at the time of analysis will be censored at the date they were last known to be alive. |
| 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 pain severity as assessed using the McGill Pain Questionnaire. Changes in pain scores will be compared between treatment groups at protocol-specified assessment time points. |
| Change From Baseline in Quality of Life | At baseline, at the end of each neoadjuvant treatment cycle, and at the preoperative assessment | Change from baseline in quality-of-life scores assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. |
| Incidence of Treatment-Emergent Adverse Events | From signing informed consent through 90 days after the last dose of study treatment | Incidence, type, and severity of treatment-emergent adverse events and serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. |
Countries
China
Contacts
CONTACTYu Zhang
Outcome results
None listed