Description:
This is a Phase 3 study to evaluate the objective response rate (ORR), in patients with
metastatic pancreatic ductal adenocarcinoma treated with relacorilant in combination with
nab-paclitaxel, according to blinded independent central review.
Title
- Brief Title: Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
- Official Title: A Phase 3 Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (RELIANT)
Clinical Trial IDs
- ORG STUDY ID:
CORT125134-553
- NCT ID:
NCT04329949
Conditions
- Metastatic Pancreatic Ductal Adenocarcinoma
Interventions
Drug | Synonyms | Arms |
---|
Relacorilant, 100 mg and 25 mg | CORT125134 | Relacorilant with nab-paclitaxel |
Nab paclitaxel | Abraxane | Relacorilant with nab-paclitaxel |
Purpose
This is a Phase 3 study to evaluate the objective response rate (ORR), in patients with
metastatic pancreatic ductal adenocarcinoma treated with relacorilant in combination with
nab-paclitaxel, according to blinded independent central review.
Detailed Description
Relacorilant is a small molecule antagonist of the glucocorticoid receptor (GR). The goals of
this study are to evaluate the efficacy, safety, and pharmacokinetics (PK) of relacorilant in
combination with nab-paclitaxel in the treatment of metastatic pancreatic ductal
adenocarcinoma.
Eligible patients are those with metastatic pancreatic adenocarcinoma (mPDAC) who have
received at least 2 prior lines of therapy for pancreatic ductal adenocarcinoma (PDAC) in any
setting, including at least 1 prior gemcitabine-based therapy and at least 1 prior
fluoropyrimidine-based therapy.
Patients will receive treatment until progressive disease (PD) (per RECIST v1.1) as
determined by the Investigator, experiencing unmanageable toxicity, or until other treatment
discontinuation criteria are met. All patients will be followed for documentation of disease
progression and survival information (i.e., date and cause of death) and subsequent
treatment.
Trial Arms
Name | Type | Description | Interventions |
---|
Relacorilant with nab-paclitaxel | Experimental | Patients will be treated with relacorilant, administered orally, once daily in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. | - Relacorilant, 100 mg and 25 mg
- Nab paclitaxel
|
Eligibility Criteria
Inclusion Criteria - Patients must have the following:
Histologically confirmed PDAC with metastatic disease. Received at least 2 prior lines of
therapy for PDAC in any setting, including at least 1 prior gemcitabine-based therapy and
at least 1 prior fluoropyrimidine-based therapy.
Received no more than 4 prior lines of cytotoxic or myelosuppressive therapy for PDAC.
A measurable lesion at baseline (within 21 days prior to the first dose of relacorilant)
per RECIST v1.1, as assessed by the Investigator.
Willingness to provide blood samples and tumor tissue (primary or metastatic) for research
purposes.
Karnofsky performance status (KPS) score of ≥70. Adequate gastrointestinal absorption. If
the patient has undergone gastric bypass surgery and/or surgery of gastrointestinal or
hepatobiliary tract, the patient must demonstrate adequate absorption as evidenced by
albumin ≥3.0 g/dL, controlled pancreatic insufficiency (if present), and lack of evidence
of malabsorption.
Adequate organ and marrow function (determined through blood and urine tests)
Exclusion Criteria - Patients must not have the following:
Pancreatic neuroendocrine tumors, lymphoma of the pancreas, acinar pancreatic cancer, or
ampullary cancer.
Known untreated parenchymal brain metastasis or have uncontrolled central nervous system
metastases. Patients must not require steroids and must be neurologically stable without
corticosteroids for a minimum of 3 weeks prior to Cycle 1 Day 1.
Clinically relevant toxicity from prior systemic cytotoxic therapies or radiotherapy that
in the opinion of the Investigator has not resolved to Grade 1 or less prior to enrollment,
including peripheral neuropathy that is ongoing and greater than Grade 1 in severity,
according to National Cancer Institute Common Terminology Criteria for Adverse Events
(NCI-CTCAE) v5.0.
History of hypersensitivity or severe reaction to either relacorilant or nab-paclitaxel, or
to similar classes of either drug.
Taken the following medications prior to enrollment:
1. An investigational product, cytotoxic chemotherapy or targeted agent within 14 days.
2. Radiotherapy within 21 days.
3. Palliative radiotherapy within 1 week of Cycle 1 Day 1, or if toxicities from
radiotherapy are Grade 2 severity or higher or have not recovered to baseline.
4. Systemic or prescription strength topical corticosteroids for the purposes of treating
a chronic nononcologic indication within 21 days.
Requirement for treatment with chronic or frequently used oral or inhaled corticosteroids
for medical conditions or illnesses (e.g., rheumatoid arthritis, asthma, or
immunosuppression after organ transplantation).
Taking a concomitant medication that is a strong CYP3A or CYP2C8 inhibitor or inducer, or a
substrate of CYP3A (cytochrome P450 3A) or CYP2C8 (cytochrome P45 2C8) and has a narrow
therapeutic window.
Concurrent treatment with mifepristone or other Glucocorticoid Receptor (GR) antagonists.
Any clinically significant uncontrolled condition(s) or any medical condition which in the
opinion of the Investigator places the patient at an unacceptably high risk for toxicities
or impair study participation or cooperation.
Any major surgery within 21 days prior to enrollment.
Endoscopic retrograde cholangiopancreatography with persistence of any of the following:
1. Bilirubin ≥1.5 × ULN (Upper Limit of Normal)
2. Amylase >2 × ULN and abdominal pain or amylase >3 × ULN (with or without symptoms)
3. Fever or signs of infection
4. Decreasing hemoglobin or signs of blood loss A history of human immunodeficiency virus
(HIV) or current chronic/active infection with hepatitis C virus (HCV) or hepatitis B
virus (HBV). (Patients with chronic or active hepatitis B as diagnosed by serologic
tests are excluded from the study. In equivocal cases, hepatitis B or C polymerase
chain reaction results may be performed and must be negative for enrollment.) A rapid
decline in KPS score or serum albumin (≥20%), or have progressive pain symptoms
indicative of rapid clinical deterioration, in the opinion of the Investigator, prior
to enrollment. These patients will become ineligible if rapid decline is observed
during the Screening Period.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective Response Rate (ORR) per Blinded Independent Central Review (BICR) |
Time Frame: | Enrollment through 24 months |
Safety Issue: | |
Description: | Percentage of patients with measurable disease at baseline who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RESIST) v1.1, according to a Blinded Independent Central Review (BICR). |
Secondary Outcome Measures
Measure: | Objective Response Rate (ORR) per Investigator Assessment |
Time Frame: | Enrollment through 24 months |
Safety Issue: | |
Description: | Percentage of patients with measurable disease at baseline who achieved confirmed complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RESIST) v1.1, according to Investigator assessment. |
Measure: | Best Overall Response (BoR) |
Time Frame: | Enrollment through 24 months |
Safety Issue: | |
Description: | To evaluate the best overall response per RESIST v1.1. |
Measure: | Duration of Response (DoR) |
Time Frame: | Time of response up to 24 months |
Safety Issue: | |
Description: | To evaluate the duration of response according to the Investigator and Blinded Independent Central Review. |
Measure: | Disease Control Rate (DCR) |
Time Frame: | 18 weeks from enrollment |
Safety Issue: | |
Description: | To evaluate patients disease control rate or complete response, partial response or stable disease at 18 weeks, as assessed by the Investigator. |
Measure: | Progression-Free Survival (PFS) |
Time Frame: | Enrollment through 24 months |
Safety Issue: | |
Description: | To evaluate progression-free survival, as assessed by the Investigator |
Measure: | Overall Survival (OS) |
Time Frame: | Enrollment through 24 months |
Safety Issue: | |
Description: | To evaluate overall survival. |
Measure: | Progression-Free Survival (PFS) |
Time Frame: | 3 months, 6 months, and 12 months after Enrollment |
Safety Issue: | |
Description: | To evaluate progression-free survival at 3, 6 and 12 months |
Measure: | Overall Survival (OS) |
Time Frame: | 3 months, 6 months, and 12 months after Enrollment |
Safety Issue: | |
Description: | To evaluate overall survival at 3, 6, and 12, months. |
Measure: | Cancer Antigen (CA)19-9 |
Time Frame: | 8 and 16 weeks from Baseline |
Safety Issue: | |
Description: | To assess cancer antigen 19-9 (CA19-9) response at 8 and 16 weeks, in patients who have elevated CA19-9 at baseline. |
Measure: | Tumor Response per EORTC criteria |
Time Frame: | 6 weeks post initiation of treatment |
Safety Issue: | |
Description: | To assess tumor response based on changes in FDG-PET scan at 6 weeks per the European Organization for Research and Treatment of Cancer (EORTC) criteria, according to the Blinded Independent Central Review (BICR) |
Measure: | Time to Progression (TTP) |
Time Frame: | From date of first treatment of relicorilant plus nab-paclitaxel until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months |
Safety Issue: | |
Description: | To evaluate the time to progression by comparing duration of disease control on prior nab-paclitaxel therapy (if applicable) and on the most recent therapy (study treatment of relacorilant and Nab-paclitaxel). |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Corcept Therapeutics |
Trial Keywords
- Pancreatic Cancer
- mPDAC
- Metastatic Pancreatic Ductal Adenocarcinoma
- Glucocorticoid Receptor
- Nab-paclitaxel
- GR Antagonist
- Relacorilant
- Abraxane
Last Updated
February 1, 2021