Relacorilant With Nab-Paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Официальное название

A Phase 2, Single-Arm Trial of Relacorilant in Combination With Nab-Paclitaxel and Gemcitabine in Chemotherapy-Naïve Patients With Metastatic Pancreatic Adenocarcinoma (TRIDENT)

Обзор

This is a 2-part, Phase 2 study to evaluate the safety, tolerability, dosing, pharmacokinetics (PK), and efficacy of relacorilant in combination with nab-paclitaxel and gemcitabine in chemotherapy-naïve patients with metastatic pancreatic adenocarcinoma (PDAC).

Подробное описание

This study will include 2 parts. In Part 1 (dose finding), approximately 6 patients will be enrolled to individual dose-finding cohorts. Cohorts will receive various dose concentrations of relacorilant, nab-paclitaxel, and gemcitabine at various dosing schedules. In all dose-finding cohorts, relacorilant will be administered orally under fed conditions, once daily for 3 days on the day before (excluding Cycle 1 Day -1), the day of, and the day after nab-paclitaxel and gemcitabine. Enrollment will be paused after each cohort has been filled until the safety review committee (SRC) provides recommendations. If maximum tolerated dose (MTD) criteria are not met in a cohort, then either a dose-finding cohort at a more intense dose and/or schedule may be enrolled, or a dose and schedule at/below the MTD may be selected as the optimal dose and schedule, and Part 2 may be initiated. If MTD criteria are met, then a dose-finding cohort at a less intense dose and/or schedule may be enrolled, or dose-finding may end without proceeding to Part 2.

In Part 2 (expansion), each patient will receive the optimal dose and schedule of relacorilant, nab-paclitaxel, and gemcitabine as identified in Part 1. Analysis of Part 2 will include data for patients from Part 1 who were enrolled in the optimal dose and schedule used in Part 2.

Вмешательства

• Препарат Relacorilant
  Relacorilant will be administered as capsules for oral dosing.
• Препарат Nab-paclitaxel
  Nab-paclitaxel will be administered via IV infusion.
• Препарат Gemcitabine
  Gemcitabine will be administered via IV infusion.

Первичные конечные точки

• Percent of Patients who Experience Dose Limiting Toxicity (DLT) (Part 1) [Срок оценки: Up to 28 days after the first dose of study treatment]
• Number of Patients with 1 or More Adverse Events (AEs) Leading to Study Drug Discontinuations or Dose Modifications (Part 1) [Срок оценки: Time of first dose up to 30 days after last dose]
• Progression-Free Survival (PFS) (Part 2) [Срок оценки: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months]

Вторичные конечные точки (12)

• Maximum Plasma Concentration (Cmax) of Relacorilant (Part 1 and Part 2) [Срок оценки: Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)]
• Area Under the Plasma Concentration-time Curve (AUC) of Relacorilant (Part 1 and Part 2) [Срок оценки: Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)]
• Cmax of Nab-paclitaxel (Part 1 and Part 2) [Срок оценки: At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)]
• AUC of Nab-paclitaxel (Part 1 and Part 2) [Срок оценки: At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)]
• Overall Survival (OS) (Part 2) [Срок оценки: From date of enrollment until the date of death from any cause, whichever comes first, assessed up to 19 months]
• Best Overall Response (BOR) (Part 2) [Срок оценки: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months]
• Objective Response Rate (ORR) (Part 2) [Срок оценки: From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months]
• Duration of Response (DoR) (Part 2) [Срок оценки: From date of first objective response until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 12 months]
• Clinical Benefit Rate (CBR) (Part 2) [Срок оценки: Week 24]
• Cancer Antigen 19-9 (CA19-9) Kinetics (Part 2) [Срок оценки: Baseline to Weeks 4, 8, and 16]
• Number of Patients with 1 or More Adverse Events (Part 2) [Срок оценки: Time of first dose up to 30 days after last dose]
• Number of Patients with Treatment-related Adverse Events (Part 2) [Срок оценки: Time of first dose up to 30 days after last dose]

Критерии участия

Критерии включения

• Signed and dated informed consent form prior to screening procedures
• Histologic diagnosis or cytologic diagnosis of pancreatic adenocarcinoma (PDAC)
• Initial diagnosis of metastatic disease occurred ≤9 weeks prior to enrollment in the study
• Life expectancy of ≥3 months
• Radiographic confirmation of metastatic disease with at least 1 distant tumor metastasis measurable on radiology imaging per RECIST version 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Able to provide informed consent and comply with protocol requirements
• Able to swallow and retain oral medication and does not have uncontrolled emesis
• Has adequate gastrointestinal absorption
• Received no prior systemic anticancer chemotherapy to treat metastatic PDAC. Treatment of PDAC with a single agent RAS inhibitor is permitted.
• If a patient received prior treatment of PDAC with chemotherapy, disease progression must have occurred >12 months after completing the last dose, and no persistent treatment-related toxicities can be present.
• Adequate organ function
• Negative pregnancy test for patients of childbearing potential
• Agree to use protocol defined precautions to avoid pregnancy

Критерии исключения

• Any major surgery within 4 weeks prior to enrollment
• Prior treatment as follows:

• Radiotherapy, surgery, chemotherapy, immunotherapy, investigational therapy for the treatment of metastatic disease
• Systemic, inhaled, or prescription strength topical corticosteroids within 5 times the half-life of the corticosteroid used prior to first dose of study drug
• Received gemcitabine or nab-paclitaxel to treat their PDAC
• Known germline or somatic breast cancer gene (BRCA) mutation
• Peripheral neuropathy from any cause >Grade 1
• Medical conditions requiring chronic or frequent treatment with corticosteroids
• History of severe hypersensitivity or severe reaction to any of study drugs or their excipients
• Concurrent treatment with mifepristone or other glucocorticoid receptor modulators.
• Uncontrolled condition(s) which, may confound the results of the trial or interfere with the patient's safety or participation
• Active infection with HIV, hepatitis C or hepatitis B virus
• Known untreated parenchymal brain metastasis or uncontrolled central nervous system metastases
• History of other malignancy within 3 years prior to enrollment
• Taking protocol-prohibited medications
• Concurrent treatment with other investigational treatment studies for cancer
• Has received a live vaccine within 30 days prior to the study start date

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 15 центров

• Site 02 — Scottsdale
• Site 04 — Los Angeles
• Site 12 — Orange
• Site 06 — Atlanta
• Site 14 — Goshen
• Site 15 — Westwood
• Site 03 — Grand Rapids
• Site 10 — East Brunswick
• … и ещё 7 центров

Идентификаторы

NCT: NCT07259317 · CORT125134-558

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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