Rimegepant Combined With AG Chemotherapy As First-Line Treatment For Metastatic Pancreatic Ductal Adenocarcinoma

Official title

A Phase Ib/II Single-Arm, Single-Center, Prospective Clinical Study Of Rimegepant Combined With AG Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Overview

This study aims to evaluate the efficacy and safety of Rimegepant combined with AG chemotherapy as first-line treatment for metastatic pancreatic cancer.

Detailed description

This is a single-center, single-arm, prospective Phase Ib/II study designed to evaluate the clinical efficacy and safety profile of Rimegepant in combination with the AG (Nab-paclitaxel plus Gemcitabine) chemotherapy regimen as first-line treatment for patients with unresectable metastatic pancreatic cancer who have not received prior anti-pancreatic cancer therapy (surgical resection excepted).

Interventions

• Drug Rimegepant plus Nab-Paclitaxel and Gemcitabine
  Rimegepant 75 mg every other day. Nab-paclitaxel 125 mg/m² and Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of a 21-day cycle.

Primary outcome measures

• Progression-Free Survival [Time frame: From randomization to disease progression or death, with follow-up for up to 2 years after treatment initiation.]

Eligibility criteria

Inclusion criteria

• The patient has good compliance, understands the study procedures, and has signed a written informed consent form.
• Age ≥ 18 years.
• Pathologically or cytologically confirmed pancreatic cancer, with imaging or pathological findings indicating unresectable pancreatic cancer with distant metastasis.
• Patients who have not received any prior treatment for pancreatic cancer (including radiotherapy, chemotherapy, or experimental therapy), except for surgical resection.
• If the patient has received neoadjuvant/adjuvant chemotherapy, the regimen must not contain AG, and the interval from the last administration to the diagnosis of recurrence must be >6 months, with no delayed toxicities.
• The patient has at least one measurable lesion according to the RECIST 1.1 criteria.
• ECOG performance status 0-1.
• Expected survival >3 months.
• Adequate organ function, defined as meeting the following criteria (blood tests to be completed within 14 days prior to enrollment):

• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Hemoglobin ≥90 g/dL
• Platelet count (PLT) ≥100 × 10⁹/L
• Total bilirubin <1.5 × upper limit of normal (ULN)
• Liver transaminases (AST \& ALT) <2.5 × ULN; for patients with liver metastases, AST/ALT ≤5 × ULN
• Serum creatinine ≤1 × ULN, or creatinine clearance ≥50 mL/min if serum creatinine >1 × ULN
• The patient has an adequate nutritional status, defined as BMI >18.5 kg/m².
• Female patients who are not pregnant or breastfeeding; sexually active men and women of childbearing potential must use effective contraception during the study and for 6 months after treatment completion.
• No contraindications to remimazolam or AG chemotherapy agents.

Exclusion criteria

• Patients with a history of other malignancies within the past 5 years, except for cured in situ carcinoma or basal cell carcinoma of the skin.
• Patients diagnosed with pulmonary fibrosis or interstitial pneumonia within 28 days prior to enrollment.
• Patients with refractory pleural effusion or ascites.
• Patients with known brain or meningeal metastases.
• Patients who used strong CYP3A4 inducers within 3 weeks prior to the first study drug administration, or strong CYP3A4/UGT1A1 inhibitors within 3 weeks prior to the first study drug administration.
• Patients who underwent major organ surgery (excluding needle biopsy, central venous catheter insertion, port catheterization, biliary obstruction stenting, percutaneous transhepatic biliary drainage, and cholecystostomy) within 4 weeks prior to the first dose of study drug, or who plan to undergo elective surgery.
• Patients with known dihydropyrimidine dehydrogenase deficiency or low activity.
• Patients with active infection, including HIV infection, or chronic HBV/HCV in the active phase (HBV DNA ≥10⁴ copies/mL or ≥2000 IU/mL; patients must receive antiviral therapy first, and can only be enrolled when HBV DNA <10⁴ copies/mL or <2000 IU/mL, with continued antiviral therapy and monitoring of liver function and HBV viral load).
• Patients with severe comorbidities, including poorly controlled diabetes despite anti-diabetic medication, clinically significant active heart disease, renal failure, liver failure, uncontrolled epilepsy, history of central nervous system disease or mental disorder, hemorrhagic peptic ulcer, ileus, or intestinal obstruction.
• Patients with severe diarrhea (grade ≥2 per NCI-CTCAE v5.0: ≥4 bowel movements per day vs baseline; moderate/severe increase in stoma output; limitation of activities of daily living).
• Patients with severe psychiatric disorders.
• Patients with grade ≥II peripheral neuropathy at present or in the past.
• Patients with known hypersensitivity to benzodiazepines, AG chemotherapy agents, or related components.
• Patients who participated in other clinical trials within 4 weeks prior to enrollment.
• Patients deemed unsuitable for the trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07475234 · E20260288

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗