Study to Evaluate CORT125134 in Combination With Nab-paclitaxel in Patients With Solid Tumors

Sponsor

Corcept Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT02762981

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

21.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: CORT125134 with nab-paclitaxel	Phase 1/Phase 2

Detailed Description

The study will consist of two segments to evaluate alternative dosing schedules of CORT125134 (Part 1) and a dose expansion which will occur once the development regimen for Segment I and Segment II has been determined (Part 2). Segment I will evaluate a continuous-dosing regimen and Segment II will evaluate an intermittent-dosing regimen. Enrollment in Segment I and Segment II will be mutually exclusive, and the two segments will enroll patients concurrently.

Segment I, Part 1: dose-escalation cohorts will be enrolled with approximately 62 patients to determine the maximum tolerated dose (MTD) and the development regimen for the continuous-dosing regimen. Treatment will be administered in 28-day cycles.

A continuous dosing cohort will be explored in patients with pancreatic cancer. Segment I, Part 2: Enrollment in Part 2 of the study (dose expansion) will occur once the development regimen for Segment I has been determined.

Segment II, Part 1: dose-escalation cohorts will be enrolled with approximately 24 patients to determine the MTD and the development regimen for the intermittent-dosing regimen. Treatment on Segment II Part I will be administered in 28-day cycles.

Segment II, Part 2: Enrollment in Part 2 of the study (dose expansion) will occur once the development regimen for Segment II has been determined.

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 1, 2016

Actual Primary Completion Date :

May 1, 2020

Actual Study Completion Date :

Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CORT125134 with nab-paclitaxel Part I - Dose Escalation: Patients will be treated with CORT125134 in combination with nab-paclitaxel at escalating dose levels in either a Continuous-Dosing Regimen or an Intermittent-Dosing Regimen. Part 2 - Dose Expansion: Expansion cohorts in the Continuous-Dosing and Intermittent-Dosing Regimens will be enrolled to better characterize the antitumor activity in patients with specific tumor types and to better define the safety profile.	Drug: CORT125134 with nab-paclitaxel CORT125134 is supplied as capsules for oral dosing. Nab-paclitaxel administered as an IV infusion. Other Names: Abraxane Nanoparticle albumin-bound paclitaxel Relacorilant

Arm

Intervention/Treatment

Experimental: CORT125134 with nab-paclitaxel

Part I - Dose Escalation: Patients will be treated with CORT125134 in combination with nab-paclitaxel at escalating dose levels in either a Continuous-Dosing Regimen or an Intermittent-Dosing Regimen. Part 2 - Dose Expansion: Expansion cohorts in the Continuous-Dosing and Intermittent-Dosing Regimens will be enrolled to better characterize the antitumor activity in patients with specific tumor types and to better define the safety profile.

Drug: CORT125134 with nab-paclitaxel

CORT125134 is supplied as capsules for oral dosing. Nab-paclitaxel administered as an IV infusion.

Other Names:

Abraxane

Nanoparticle albumin-bound paclitaxel

Relacorilant

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose of CORT125134 in Combination with nab-paclitaxel [24 months]
The Maximum Tolerated Dose and the development regimen of CORT125134 with nab-paclitaxel in patients with solid tumors as measured by the number of patients with dose-limiting toxicities

Secondary Outcome Measures

Number of Treatment-Related Adverse Events as Assessed by CTCAE version 4.0 for Patients with Solid Tumors Treated with CORT125134 in combination with nab-paclitaxel [28 days after last patient dosed]
To characterize the safety profile of the combination of CORT125134 and nab-paclitaxel.

Other Outcome Measures

Objective response rate [ORR], progression free survival [PFS], and overall survival [OS] patients with solid tumors [12 months from the enrollment of the final subject]
To characterize the preliminary anticancer activity (objective response rate [ORR], progression free survival [PFS], and overall survival [OS]) of the combination of CORT125134 and nab-paclitaxel in patients with solid tumors in a dose-finding phase and in patients with specific tumor types.
Objective response rate [ORR], progression free survival [PFS], and overall survival [OS] in patients with GR-positive or GR negative solid tumors. [12 months from the enrollment of the final subject]
The preliminary anticancer activity (ORR, PFS, and OS) of the combination of CORT125134 and nab-paclitaxel in patients with GR-positive or GR negative solid tumors.
Pharmacokinetics (PK) and exposure-response [2 weeks after last patient Cycle 1 Day 1]
To characterize the pharmacokinetics (PK) and exposure-response of the combination of CORT125134 and nab paclitaxel in patients with solid tumors in a dose-finding phase and in patients with specific tumor types.
Pharmacodynamics (PD) indicative of modulation of GR function, including hormonal changes and FKBP5 [Baseline through end of treatment]
The pharmacodynamics (PD) of the combination of CORT125134 and nab-paclitaxel indicative of modulation of GR function, including hormonal changes and FKBP5.
Molecular, cellular, and soluble markers in peripheral blood and/or tumor tissue [Baseline through end of treatment]
To evaluate molecular, cellular, and soluble markers in peripheral blood and/or tumor tissue that may be relevant to the mechanism of action of or response/resistance to CORT125134.
Pharmacogenomic (PG) markers [Baseline]
To evaluate pharmacogenomic (PG) markers to assess genetic factors affecting drug metabolism and transporters.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	038	Scottsdale	Arizona	United States	85258
2	014	San Francisco	California	United States	94115
3	001	Chicago	Illinois	United States	60637
4	013	Ogden	Utah	United States	84403