Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Metastatic Pancreatic Ductal Adenocarcinoma Clinical Trial

— RELIANT  

Official title:

A Phase 3 Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (RELIANT)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04329949
• Other study ID #: CORT125134-553
• Status: Terminated
• Phase: Phase 3
• Start date: June 30, 2020
• Est. completion date: March 25, 2022

Study information

• Verified date: October 2023
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, open-label study to evaluate the objective response rate (ORR), in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with relacorilant in combination with nab-paclitaxel, according to blinded independent central review.

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 mPDAC who have received at least 2 prior lines of therapy for pancreatic ductal adenocarcinoma 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. completion date: March 25, 2022
• Est. primary completion date: August 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (cytochrome P450 3A) or CYP2C8 inhibitor or inducer, or a substrate of CYP3A or CYP2C8 and has a narrow therapeutic window

Concurrent treatment with mifepristone or other 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• Relacorilant, 100 mg and 25 mg
Relacorilant is supplied as capsules for oral dosing.
• Nab-paclitaxel
Nab-paclitaxel is administered as IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.

Locations

Country	Name	City	State
United States	Site #009	Atlanta	Georgia
United States	Site #032	Aurora	Colorado
United States	Site #065	Baltimore	Maryland
United States	Site #182	Buffalo	New York
United States	Site #077	Columbus	Ohio
United States	Site #058	Detroit	Michigan
United States	Site #171	Duarte	California
United States	Site #184	Goshen	Indiana
United States	Site #175	Knoxville	Tennessee
United States	Site #076	Los Angeles	California
United States	Site #176	Nashville	Tennessee
United States	Site #044	New York	New York
United States	Site #222	New York	New York
United States	Site #185	Omaha	Nebraska
United States	Site #172	Pittsburgh	Pennsylvania
United States	Site #038	Scottsdale	Arizona
United States	Site #173	Seattle	Washington
United States	Site #186	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)	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 (RECIST) v1.1, as assessed by Blinded Independent Central Review (BICR). Tumor assessment consisted of computerized tomography (CT) scan or, with Sponsor approval, magnetic resonance imaging (MRI). CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the sum of the diameters (SOD) of target lesions.	Baseline and up to 32 weeks
Secondary	Objective Response Rate (ORR) Per Investigator Assessment	Percentage of patients with measurable disease at baseline who achieved confirmed CR or PR per RECIST v1.1, as assessed by the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the SOD of target lesions.	Baseline and up to 48 weeks
Secondary	Best Overall Response (BOR)	To evaluate the best overall response of CR, PR, stable disease (SD), or PD per RECIST v1.1. as assessed by BICR. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as =20% increase in the SOD of target lesions or the appearance of one or more new lesions.	Baseline and up to 32 weeks
Secondary	Duration of Response (DOR)	To evaluate the duration of response as the time of objective response (CR or PR) to the time of disease progression or death, per RECIST v1.1 as assessed by BICR and the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the SOD of target lesions. PD was defined as =20% increase in the SOD of target lesions or the appearance of one or more new lesions.	Time of response up to 32 weeks
Secondary	Disease Control Rate (DCR)	To evaluate patients disease control rate of CR, PR, or SD at 18 weeks, per RECIST v1.1 as assessed by the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. CR was defined as disappearance of all target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	Enrollment through 18 weeks
Secondary	Progression-Free Survival (PFS)	To evaluate PFS as median time to disease progression per RECIST v1.1, or death, as assessed by BICR. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. Disease progression was defined as =20% increase in the SOD of target lesions or the appearance of one or more new lesions.	Baseline and up to 31 weeks.
Secondary	Overall Survival (OS)	To evaluate OS as median time to death by any cause.	Baseline and up to 70 weeks
Secondary	Progression-Free Survival (PFS)	To evaluate PFS as the percentage of patients who are progression-free at 3, 6, and 12 months per RECIST v1.1, as assessed by BICR. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. Disease progression was defined as =20% increase in the SOD of target lesions or the appearance of one or more new lesions.	Enrollment through 3 months, 6 months, and 12 months
Secondary	Overall Survival (OS)	To evaluate OS as the percentage of patients surviving at 3, 6, and 12, months.	Enrollment through 3 months, 6 months, and 12 months
Secondary	Cancer Antigen (CA)19-9	To assess cancer antigen 19-9 (CA19-9) response at 8 and 16 weeks in patients who have elevated CA19-9 at baseline. Response was defined as =50% reduction in CA19-9.	Enrollment through 8 weeks and 16 weeks
Secondary	Tumor Response Per European Organization for Research and Treatment of Cancer (EORTC) Criteria	To assess tumor response based on changes in fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at 6 weeks per the EORTC criteria, as assessed by BICR.	Enrollment through 6 weeks
Secondary	Time to Progression (TTP)	To evaluate TTP as median time to disease progression per RECIST v1.1, as assessed by the Investigator. Tumor assessment consisted of CT scan or, with Sponsor approval, MRI. Disease progression was defined as =20% increase in the SOD of target lesions or the appearance of one or more new lesions.	Baseline and up to 32 weeks