Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
Condition: Metastatic Pancreatic Ductal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Relacorilant, 100 mg and 25 mg; Nab-paclitaxel
Intervention description: Relacorilant is supplied as capsules for oral dosing.; Nab-paclitaxel is administered as IV infusion over 30 minutes on Days 1, 8, and 15 of each 28-day cycle.
Intervention MeSH terms: Paclitaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreatic Cancer; mPDAC; Metastatic Pancreatic Ductal Adenocarcinoma; Glucocorticoid Receptor; Nab-paclitaxel; GR Antagonist; Relacorilant; Abraxane

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.
    

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 (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.