Clinical Trials /

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

NCT04329949

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.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
Relacorilant, 100 mg and 25 mgCORT125134Relacorilant with nab-paclitaxel
Nab paclitaxelAbraxaneRelacorilant 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

NameTypeDescriptionInterventions
Relacorilant with nab-paclitaxelExperimentalPatients 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:Recruiting
Lead Sponsor:Corcept Therapeutics

Trial Keywords

  • Pancreatic Cancer
  • mPDAC
  • Metastatic Pancreatic Ductal Adenocarcinoma
  • Glucocorticoid Receptor
  • Nab-paclitaxel
  • GR Antagonist
  • Relacorilant
  • Abraxane

Last Updated

July 7, 2020