Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma Which Produces Too Much Stress Hormone (Cortisol)

February 22, 2024 updated by: Corcept Therapeutics

A Phase 1b, Open-Label Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production

This study will investigate the safety and efficacy of Relacorilant in combination with Pembrolizumab for Patients with Adrenocortical Carcinoma which Produces Too Much Stress Hormone (Cortisol).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Relacorilant is a small molecule antagonist of the glucocorticoid receptor (GR).

The goal of this study is to assess the safety and efficacy of relacorilant when given in combination with pembrolizumab in patients with advanced adrenocortical carcinoma (ACC) which produces too much stress hormone (cortisol). Too much stress hormone (cortisol) is also called glucocorticoid (GC) excess.

Eligible patients are those with advanced ACC that produces too much cortisol.

Patients will receive treatment until progressive disease (PD) (per RECIST v1.1) is confirmed, experience unmanageable toxicity, or until other treatment discontinuation criteria are met. All patients will be followed for documentation of disease progression, survival information (i.e., date and cause of death) and subsequent treatment.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Site #150, Stanford Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Site #007, Moffitt Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Site #074, University of Michigan Medical School
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Site #030 Mayo Clinic
    • New York
      • New York, New York, United States, 10022
        • Site #051, Memorial Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Site #183, The University of Texas M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed ACC (advanced unresectable and/or metastatic)
  • Measurable disease based upon RECIST v1.1 as determined by the Investigator.
  • Documented GC excess (too much cortisol).
  • For patients who have received mitotane within 3 months prior to screening, mitotane levels must be <4 mg/L at screening.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  • Adequate organ and bone marrow function (determined through blood and urine tests)
  • Negative pregnancy test for patients of childbearing potential at the Screening and every 6 weeks (+ or - 7 days) in female patients of childbearing potential.

Exclusion Criteria:

  • Major surgery within 4 weeks prior to enrollment. If the participant underwent major surgery, they must have recovered adequately prior to starting study treatment.
  • Have received and responded (complete response [CR] or partial response [PR]) to prior treatment with any prior checkpoint inhibitor or any other agents targeting T-cell stimulation pathways
  • Taking a concomitant medication that is a strong Cytochrome P450 3A (CYP3A) inducer, or that is a substrate of CYP3A with a narrow therapeutic index
  • Known untreated parenchymal brain metastasis or have uncontrolled central nervous system (CNS) metastases. Patients must not require steroids and must be neurologically stable without corticosteroids for a minimum of 3 weeks prior to the commencement of the study. Patients with neurologic symptoms must undergo a CT/MRI to rule out occult CNS metastases.
  • Requirement for chronic systemic GC treatment, such as active autoimmune disease requiring systemic treatment (corticosteroids or other immunosuppressive medication)
  • Patients requiring inhaled glucocorticoids but have no other alternative treatment option if their condition deteriorates during the study.
  • Clinically relevant toxicity from prior systemic cytotoxic therapies or radiotherapy that in the opinion of the Investigator has not resolved to NCI-CTCAE v5.0 Grade 1 or less prior to the first dose of relacorilant.

  • Treated with the following prior to the first dose of relacorilant:

    1. Any investigational product, systemic anticancer therapy, or radiation therapy within 21 days
    2. Antibodies or anticancer vaccines within 60 days
    3. Mifepristone or other GR antagonists within 5 half-lives of these medications
    4. Adrenostatic medications within 5 half-lives of these medications
  • History of severe hypersensitivity to another monoclonal antibody
  • Other concurrent cancer or a history of another invasive malignancy within the last 3 years that has a likelihood of recurrence of >30% within the next 5 years. Adequately treated basal and squamous skin cancers, ductal carcinoma in situ, cervical cancer, prostate cancer, non-muscle invasive urothelial cancer or other tumors curatively treated with no evidence of disease are permissible.
  • Human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus or hepatitis B virus including: Chronic or active hepatitis B as diagnosed by serologic tests. In equivocal cases, hepatitis B or C polymerase chain reaction may be performed and must be negative for enrollment.

  • Clinically significant uncontrolled condition(s) or a condition which, in the opinion of the Investigator, may confound the results of the trial or interfere with the patient's participation, including but not limited to:

    1. Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 3 months before study entry.
    2. Active infection that requires parenteral antibiotics.
    3. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Relacorilant in Combination with Pembrolizumab
Participants will be treated on Day -3 to Day 1 (Cohort 1 under fasting conditions) or Day -6 to Day 1 (Cohort 2 under fed conditions) for Cycle 1 only. During the lead-in period, 300 mg relacorilant will be administered daily for 4 -7 days. Patients will receive their first pembrolizumab infusion on Cycle 1 Day 1. The participants will then receive combined treatment from Cycle 1 Day 1 until confirmed PD or unacceptable toxicity. Pembrolizumab will be administered every 6 weeks (on Day 1 of each 42-day cycle) and relacorilant will be administered daily. Optional Cohort 3 will lead-in with 400 mg relacorilant once daily for 7 days and combined treatment of relacorilant and pembrolizumab, depending on PD and toxicity.
Drug: Relacorilant
Relacorilant, 100 mg soft gel capsules orally once daily
Other Names:
  • CORT125134
Drug: Pembrolizumab
Pembrolizumab 400 mg infusion every 6 weeks
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting Toxicity (DLT)
Time Frame: Up to 12 weeks
Evaluate the percentage of patients with a dose-limiting toxicity
Up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-Progression Rate (NPR)
Time Frame: 24 weeks from enrollment
Evaluate the non-progression rate (NPR) per RECIST v1.1
24 weeks from enrollment
Progression-Free Survival (PFS)
Time Frame: From date of first treatment, until the date of first documented progression or date of death from any cause, whichever came first, up to month 24
Evaluate progression-free survival (PFS) per RECIST v1.1
From date of first treatment, until the date of first documented progression or date of death from any cause, whichever came first, up to month 24
Number of Participants with Adverse Events
Time Frame: Up to 37 days post-treatment
Adverse events (AEs) by severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
Up to 37 days post-treatment
Plasma Concentrations of Relacorilant in Combination with Pembrolizumab in Patients with Advanced ACC and Glucocorticoid Excess
Time Frame: Up to 24 months
Plasma concentrations of relacorilant in combination with pembrolizumab will be calculated in patients with advanced ACC and glucocorticoid excess
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Corcept Therapeutics

Investigators

  • Study Director: Andreas G Moraitis, MD, Corcept Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2020

Primary Completion (Actual)

October 17, 2023

Study Completion (Actual)

January 12, 2024

Study Registration Dates

First Submitted

April 30, 2020

First Submitted That Met QC Criteria

April 30, 2020

First Posted (Actual)

May 4, 2020

Study Record Updates

Last Update Posted (Actual)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 22, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CORT125134-551

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Adrenocortical Carcinoma

Clinical Trials on Relacorilant

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Germany

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe