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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02762981
• Other study ID #: CORT125134-550
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 23, 2016
• Est. completion date: September 12, 2020

Study information

• Verified date: November 2022
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: September 12, 2020
• Est. primary completion date: May 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• Relacorilant with nab-paclitaxel
Relacorilant is supplied as capsules for oral dosing. Nab-paclitaxel administered as an IV infusion.

Locations

Country	Name	City	State
United States	001	Chicago	Illinois
United States	013	Ogden	Utah
United States	014	San Francisco	California
United States	038	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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)
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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)

External 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)