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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Relacorilant will be administered as capsules for oral dosing.
Nab-paclitaxel will be administered via IV infusion.
Gemcitabine will be administered via IV infusion.
Site 02
Scottsdale, Arizona, United States
RECRUITINGPercent of Patients who Experience Dose Limiting Toxicity (DLT) (Part 1)
The percentage of patients with a DLT is used to estimate maximum tolerated dose (MTD), the most intense dose/schedule among those evaluated at which \<33% of patients experience DLT.
Time frame: 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)
Time frame: Time of first dose up to 30 days after last dose
Progression-Free Survival (PFS) (Part 2)
To evaluate PFS as the time from enrollment until first documented progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as determined by the Investigator, or death due to any cause, whichever comes first.
Time frame: 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
Maximum Plasma Concentration (Cmax) of Relacorilant (Part 1 and Part 2)
Time frame: 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)
Time frame: Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days)
Cmax of Nab-paclitaxel (Part 1 and Part 2)
Time frame: At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)
AUC of Nab-paclitaxel (Part 1 and Part 2)
Time frame: At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days)
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Site 04
Los Angeles, California, United States
Site 12
Orange, California, United States
RECRUITINGSite 17
Jacksonville, Florida, United States
RECRUITINGSite 06
Atlanta, Georgia, United States
RECRUITINGSite 14
Goshen, Indiana, United States
RECRUITINGSite 15
Westwood, Kansas, United States
RECRUITINGSite 03
Grand Rapids, Michigan, United States
RECRUITINGSite 18
Rochester, Minnesota, United States
RECRUITINGSite 10
East Brunswick, New Jersey, United States
RECRUITING...and 10 more locations
Overall Survival (OS) (Part 2)
Time frame: 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)
Time frame: 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)
To evaluate the proportion of patients with measurable disease at Baseline who attain complete response (CR) or partial response (PR) by RECIST version 1.1.
Time frame: 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)
To evaluate DOR as the time from the first CR or PR to first documented PD or death, whichever comes first.
Time frame: 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)
To evaluate clinical benefit rate as the proportion of patients who attain CR, PR, or stable disease (SD) at Week 24 as per RECIST version 1.1.
Time frame: Week 24
Cancer Antigen 19-9 (CA19-9) Kinetics (Part 2)
To evaluate change in CA19-9 from baseline in patients who had an elevated baseline CA19-9 and change in CA19-9 at Weeks 4, 8, and 16 from baseline in all patients.
Time frame: Baseline to Weeks 4, 8, and 16
Number of Patients with 1 or More Adverse Events (Part 2)
Time frame: Time of first dose up to 30 days after last dose
Number of Patients with Treatment-related Adverse Events (Part 2)
Time frame: Time of first dose up to 30 days after last dose
Number of Patients with Adverse Events by Severity (Part 2)
Time frame: Time of first dose up to 30 days after last dose
Number of Patients With 1 or More Adverse Events Leading to Study Drug Discontinuation (Part 2)
Time frame: Time of first dose up to 30 days after last dose