Clinical trial NCT02762981: Study to Evaluate Relacorilant (CORT125134) in Combination With Nab-paclitaxel in Participants With Solid Tumors
Official title: Phase 1/2 Study of CORT125134 in Combination With Nab-paclitaxel in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Keywords: CORT125134
nab-paclitaxel
Triple-Negative Breast Cancer
Ovarian Epithelial Cancer
GR Antagonist
Glucocorticoid Receptor Antagonist
Pancreatic Cancer
Solid Tumors
Relacorilant
Abraxane
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-05-05
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicity
timeFrame: Up to completion of Cycle 1 (up to 28 days)
Secondary outcomes:
measure: Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant
timeFrame: 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 outcomes:
measure: Objective Response Rate
timeFrame: Up to 512 days
measure: Clinical Benefit Rate
timeFrame: Up to 512 days
measure: Duration of Response
timeFrame: From the time of response up to the last disease assessment (up to 512 days)
measure: Progression-free Survival
timeFrame: Up to 512 days
measure: Overall Survival
timeFrame: Up to 512 days
measure: Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level
timeFrame: Up to 512 days
measure: Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant
timeFrame: 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
measure: Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel
timeFrame: 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
measure: Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant
timeFrame: 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
measure: Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel
timeFrame: 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
Locations:
city: Scottsdale
country: United States
facility: 038
state: Arizona
city: San Francisco
country: United States
facility: 014
state: California
city: Chicago
country: United States
facility: 001
state: Illinois
city: Ogden
country: United States
facility: 013
state: Utah
Study officials:
affiliation: Corcept Therapeutics
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.