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Rimegepant-Sensitized Neoadjuvant Chemoimmunotherapy for Oral or Oropharyngeal Squamous Cell Carcinoma

ConditionsOral Squamous Cell Carcinoma (OSCC)Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorShanghai Zhongshan Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Rimegepant

    Drug

    Rimegepant 75 mg will be administered orally every other day from the initiation until the completion of neoadjuvant chemoimmunotherapy.

  • Tislelizumab

    Drug

    Tislelizumab 200 mg will be administered by intravenous infusion on Day 1 of each 3-week treatment cycle for two cycles.

  • Nab-paclitaxel

    Drug

    Nab-paclitaxel 260 mg/m² will be administered by intravenous infusion on Day 2 of each 3-week treatment cycle for two cycles.

  • Cisplatin

    Drug

    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.

Treatment groups

220 Participants
are divided into 3 treatment groups
Group A: Safety Run-In Combination ArmExperimental treatment 4 interventions
Group B: Randomized Combination ArmExperimental treatment 4 interventions
Group C: Randomized Control ArmActive comparator 3 interventions

Trial outcomes

Primary outcomes

1

Major Pathological Response Rate

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.

Time frame
At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment

Secondary outcomes

1

Pathological Complete Response Rate

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.

Time frame
At pathological assessment of the definitive surgical specimen after completion of two 3-week cycles of neoadjuvant treatment
2

Objective Response Rate

Percentage of participants with a complete response or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1.

Time frame
From baseline to preoperative radiographic assessment after completion of two 3-week cycles of neoadjuvant treatment
3

Event-Free Survival

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.

Time frame
From randomization to the first event or censoring, assessed up to 5 years
4

Overall Survival

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.

Time frame
From randomization until death or censoring, assessed up to 5 years

Other outcomes

1

Change From Baseline in Peripheral Blood Immune Cell Subset Proportions Assessed by Multiparameter Flow Cytometry

Multiparameter flow cytometry will be used to quantify major immune cell subsets in peripheral blood mononuclear cells, including CD4+ T cells, CD8+ T cells, B cells, natural killer cells, and monocytes. Each immune cell subset will be reported as a percentage of total viable peripheral blood mononuclear cells. Changes from baseline will be reported in percentage points at each post-baseline assessment.

Time frame
At baseline; at the end of Cycle 1 (Day 21); at the end of Cycle 2 (Day 42); and on the day of definitive surgery before anesthesia
2

Change From Baseline in Tumor-Infiltrating Immune Cell Subset Proportions Assessed by Single-Cell RNA Sequencing

Single-cell RNA sequencing will be used to quantify tumor-infiltrating immune cell subsets in paired pretreatment biopsy and definitive surgical specimens, including T cells, B cells, natural killer cells, macrophages, and other myeloid cells. Each immune cell subset will be reported as a percentage of all viable cells captured in the corresponding specimen. Changes from baseline will be reported in percentage points.

Time frame
At baseline, using the pretreatment biopsy obtained before Cycle 1, and at definitive surgery after completion of two 21-day cycles of neoadjuvant treatment
3

CGRP Pathway Biomarkers

Changes in the expression of biomarkers related to the calcitonin gene-related peptide signaling pathway in tumor tissue and/or peripheral blood.

Time frame
At baseline, using peripheral blood and the pretreatment tumor biopsy obtained before Cycle 1, and at definitive surgery after completion of two 21-day cycles of neoadjuvant treatment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Shanghai Zhongshan Hospital

Lead sponsor

Pfizer

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: