Adenocarcinoma, Carcinoma, Pancreatic Ductal
Conditions
Keywords
Pancreatic, Adenocarcinoma, PDAC, Pancreas
Brief summary
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).
Detailed description
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.
Interventions
DRUGRelacorilant
Relacorilant will be administered as capsules for oral dosing.
DRUGNab-paclitaxel
Nab-paclitaxel will be administered via IV infusion.
DRUGGemcitabine
Gemcitabine will be administered via IV infusion.
Sponsors
Corcept Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* Any major surgery within 4 weeks prior to enrollment * Prior treatment as follows: 1. Radiotherapy, surgery, chemotherapy, immunotherapy, investigational therapy for the treatment of metastatic disease 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients who Experience Dose Limiting Toxicity (DLT) (Part 1) | Up to 28 days after the first dose of study treatment | 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. |
| Number of Patients with 1 or More Adverse Events (AEs) Leading to Study Drug Discontinuations or Dose Modifications (Part 1) | Time of first dose up to 30 days after last dose | — |
| Progression-Free Survival (PFS) (Part 2) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of Relacorilant (Part 1 and Part 2) | 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) | Pre- and postdose on Cycle 1 Day 15 (each cycle is 28 days) | — |
| Cmax of Nab-paclitaxel (Part 1 and Part 2) | At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days) | — |
| AUC of Nab-paclitaxel (Part 1 and Part 2) | At serial timepoints postdose on Cycle 1 Day 15 (each cycle is 28 days) | — |
| Overall Survival (OS) (Part 2) | 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) | 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) | 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 | 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. |
| Duration of Response (DoR) (Part 2) | 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 | To evaluate DOR as the time from the first CR or PR to first documented PD or death, whichever comes first. |
| Clinical Benefit Rate (CBR) (Part 2) | Week 24 | 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. |
| Cancer Antigen 19-9 (CA19-9) Kinetics (Part 2) | Baseline to Weeks 4, 8, and 16 | 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. |
| Number of Patients with 1 or More Adverse Events (Part 2) | Time of first dose up to 30 days after last dose | — |
| Number of Patients with Treatment-related Adverse Events (Part 2) | Time of first dose up to 30 days after last dose | — |
| Number of Patients with Adverse Events by Severity (Part 2) | 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 of first dose up to 30 days after last dose | — |
Countries
United States
Contacts
CONTACTCorcept Therapeutics
STUDY_DIRECTORAdrian Jubb
Corcept Therapeutics
Outcome results
None listed