Study to Evaluate Relacorilant (CORT125134) in Combination With Nab-paclitaxel in Participants With Solid Tumors

Phase 1/2 Study of CORT125134 in Combination With Nab-paclitaxel in Patients With Solid Tumors

The purpose of this study was to assess the safety of the combination of relacorilant (CORT125134), a novel glucocorticoid receptor (GR) antagonist, and nab- paclitaxel in participants with solid tumors and to determine the preliminary efficacy of the combination of relacorilant and nab-paclitaxel. The structure for the study was a single arm, non-randomized, open- label, multicenter trial with no control group.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Relacorilant with nab-paclitaxel

Detailed Description

The study consisted of two segments to evaluate alternative dosing schedules of relacorilant administered at escalating dose levels. Segment I was to evaluate a continuous-dosing regimen and Segment II was to evaluate an intermittent-dosing regimen. Enrollment in Segment I and Segment II were mutually exclusive, and the two segments enrolled participants concurrently.

In Segment I continuous-dosing cohorts, participants received a single nab-paclitaxel lead-in infusion on Day 1 of Week -2 before Cycle 1, and oral relacorilant lead-in once-daily of Week -1 before Cycle 1. After the Data Review Committee review of data for 2 dose levels, the nab-paclitaxel lead-in was discontinued. The lead-in period was followed by oral relacorilant administered continuously once daily, in combination with nab-paclitaxel infusions on Days 1, 8, and 15 of each 28-day cycle. Segment 1 enrolled a total of 64 participants.

In Segment II intermittent-dosing cohorts, participants received a single relacorilant lead-in dose on Day -1 before Cycle 1, followed by oral relacorilant, administered intermittently the day before, the day of, and the day after nab-paclitaxel infusions on Days 1, 8, and 15 of each 28-day cycle. Segment II enrolled a total of 21 participants.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • 038
  • California
    • San Francisco, California, United States, 94143
      • 014
  • Illinois
    • Chicago, Illinois, United States, 60637
      • 001
  • Utah
    • Ogden, Utah, United States, 84403
      • 013

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with advanced or metastatic solid tumors who have disease progression after treatment with available therapies and for whom nab-paclitaxel treatment is appropriate.
• Measurable or evaluable disease.
• Up to 3 prior cytotoxic chemotherapeutics regimens or myelosuppressive therapies in the advanced setting.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• For Part 2 Only: Platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer, or Triple Negative Breast Cancer with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in at least 1 lesion, that in the opinion of the Investigator is appropriate to treat with nab-paclitaxel.

Exclusion Criteria:

• Any major surgery within 4 weeks prior to the first dose of study drug.
• Some protocol specified treatments prior to the first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relacorilant with nab-paclitaxel; Participants will be treated with relacorilant in combination with nab-paclitaxel at escalating dose levels in either a Continuous-Dosing Regimen or an Intermittent-Dosing Regimen.	Drug: Relacorilant with nab-paclitaxel; Relacorilant is supplied as capsules for oral dosing. Nab-paclitaxel administered as an IV infusion.; Other Names: Abraxane; Nanoparticle albumin-bound paclitaxel; CORT125134

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicity	The Maximum Tolerated Dose and the development regimen of relacorilant with nab-paclitaxel was determined by the number of participants with dose-limiting toxicities as defined in the protocol.	Up to completion of Cycle 1 (up to 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant	Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	Up to 28 days after the last dose of study drug (Segment I: up to approximately 2.5 years, Segment II: up to approximately 1.5 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate is defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as best response of complete response (CR) or partial response (PR) from the start of relacorilant or nab-paclitaxel, whichever is earliest, across all time points during study observation period (including both confirmed and unconfirmed responses).	Up to 512 days
Clinical Benefit Rate	Clinical benefit rate is defined as the participants who have achieved CR or PR (including both confirmed and unconfirmed responses), or stable disease for 16 weeks or greater.	Up to 512 days
Duration of Response	Duration of response (DOR) is defined as the date that criteria are met for CR or PR until the first date that progressive disease or death is objectively documented, whichever occurs first. Participants with no documentation of disease progression or death on-study are censored at the date of last available tumor assessment	From the time of response up to the last disease assessment (up to 512 days)
Progression-free Survival	Progression-free survival is defined as the time from date of first dose of relacorilant or nab-paclitaxel, whichever is earliest, to the date of documented disease progression per RECIST v1.1 or death for any cause, whichever occurs first. Participants with no documentation of disease progression or death on-study are censored at the date of last available tumor assessment.	Up to 512 days
Overall Survival	Overall survival is defined as the time from date of the first dose of relacorilant or nab paclitaxel, whichever is earliest, to the date of death for any cause. Participants with no documentation of death on-study are censored at the date at which they are last known to be alive.	Up to 512 days
Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level	Best response is defined by RECIST v1.1 as the best response recorded from the date of the first dose of relacorilant or nab-paclitaxel, whichever is earliest, across all time points during study observation period (including both confirmed and unconfirmed responses).	Up to 512 days
Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant		Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel		Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant		Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel		Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Medical Monitor, Corcept Therapeutics

Publications and helpful links

General Publications

• Pivonello R, Munster PN, Terzolo M, Ferrigno R, Simeoli C, Puglisi S, Bali U, Moraitis AG. Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant. Front Endocrinol (Lausanne). 2022 Jan 4;12:793262. doi: 10.3389/fendo.2021.793262. eCollection 2021.

Helpful Links

• A phase 1/2 study of relacorilant + nab-paclitaxel (nab-pac) in patients (pts) with solid tumors: The dose-finding phase
• Relacorilant (RELA) with nab-paclitaxel (NP): Safety and activity in patients with pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer (OvCA)

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2016
• Primary Completion (Actual): May 12, 2020
• Study Completion (Actual): September 12, 2020

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: November 9, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Solid Tumors; CORT125134; nab-paclitaxel; Triple-Negative Breast Cancer; Ovarian Epithelial Cancer; GR Antagonist; Glucocorticoid Receptor Antagonist; Relacorilant; Abraxane
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: CORT125134-550

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No