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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04373265
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : February 25, 2022
Information provided by (Responsible Party):
Corcept Therapeutics

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Adrenocortical Carcinoma Drug: Relacorilant Drug: Pembrolizumab Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production
Actual Study Start Date : September 30, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : July 31, 2023

Arm Intervention/treatment
Experimental: Relacorilant in Combination with Pembrolizumab

Patients will treated with a lead-in of 300 mg relacorilant once daily from Day -3 to Cycle 1 Day 1 prior to the first dose of pembrolizumab. From Cycle 1 Day 1 until confirmed p or unacceptable toxicity with relacorilant and pembrolizumab. Pembrolizumab will be administered every 6 weeks (on Day 1 of each 42-day cycle) and relacorilant will be administered daily.

On Cycle 1 Day 2, the patient's dose increases to 100 mg relacorilant once daily for 2 weeks. The patient's relacorilant doses may then escalate by 100-mg increments every 2 weeks based on tolerability until they reach 400 mg relacorilant once daily.

For patients who tolerate the 400 mg relacorilant once daily, but their Cushing-syndrome symptoms persist, further dose escalation in 100-mg increments to a maximum of 600 mg relacorilant once daily may be considered after approval of the Medical Monitor and as long as the patient's AUC0-24 at their current dose does not exceed the maximum allowable exposure.

Drug: Relacorilant
Relacorilant, 100 mg soft gel capsules orally once daily
Other Name: CORT125134

Drug: Pembrolizumab
Pembrolizumab 400 mg infusion every 6 weeks
Other Name: Keytruda

Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ 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 the percentage of patients with measurable disease at baseline who achieve confirmed complete response (CR) or partial response (PR) per RECIST v1.1

  2. Dose-limiting Toxicity (DLT) [ Time Frame: Up to 9 weeks ]
    Evaluate the percentage of patients with a dose-limiting toxicity

Secondary Outcome Measures :
  1. Non-Progression Rate (NPR) [ Time Frame: 24 weeks from enrollment ]
    Evaluate the non-progression rate (NPR) per RECIST v1.1

  2. 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 ]
    To evaluate progression-free survival (PFS) per RECIST v1.1

  3. Overall Survival (OS) [ Time Frame: From date of first treatment, until the date of death from any cause, up to month 24 ]
    To evaluate overall survival (OS)

  4. Duration of response (DOR) [ Time Frame: From date of response, until the date of first documented progression or date of death from any cause, whichever came first, up to month 24 ]
    To evaluate the duration of response (DOR) per RECIST v1.1 (in patients with objective response)

  5. Clinical manifestations of cortisol excess [ 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 ]
    To assess the effect of relacorilant in combination with pembrolizumab on the clinical manifestations of cortisol excess (e.g. hypertension and diabetes mellitus)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: Patients must have the following:

  • 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).
  • If received mitotane, have a mitotane level <4mg/L at within 3 months prior to Screening. Mitotane testing is not required for patients who have not received mitotane within 3 months of Screening, nor for patients who have a mitotane test result of less than 4 mg/L after their last dose of mitotane. Note: The mitotane level may be screened/retested multiple times to confirm that the level is trending down and reaches the protocol eligibility requirement.
  • 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: Patients must not have the following:

  • 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 (CR or PR) to prior treatment with any prior treatment with a programmed cell death protein 1 (anti-PD-1),PD-1 Ligand 1 (anti-PD-L1), or PD-1 Ligand 2 (anti-PD-L2) therapy,
  • Prior therapy with anti-Cluster of Differentiation (CD)137, cytotoxic T-lymphocyte-associated (CTLA) proteinCTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell stimulation or checkpoint 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 (e.g., ketoconazole, metyrapone, etomidate, or fluconazole) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04373265

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Contact: Corcept Therapeutics 650-327-3270
Contact: Corcept Therapeutics 650-327-3270

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United States, California
Site #150, Stanford Cancer Center Recruiting
Stanford, California, United States, 94305
United States, Florida
Site #007, Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
United States, Michigan
Site #074, University of Michigan Medical School Recruiting
Ann Arbor, Michigan, United States, 48109
United States, New York
Site #051, Memorial Hospital Recruiting
New York, New York, United States, 10022
United States, Texas
Site #183, The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Corcept Therapeutics
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Study Director: Andreas G Moraitis, MD Corcept Therapeutics
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Responsible Party: Corcept Therapeutics Identifier: NCT04373265    
Other Study ID Numbers: CORT125134-551
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: February 25, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Corcept Therapeutics:
Adrenocortical Carcinoma
Adrenal Carcinoma
Adrenal Autonomy
Excess Glucocorticoid
Type 2 Diabetes
Impaired Glucose Tolerance
Cushing syndrome
Moon Face
Dorsocervical Fat Pad
Glucocorticoid Receptor
GR Antagonist
Adrenal Corticotropic Hormone (ACTH)
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Pathologic Processes
Additional relevant MeSH terms:
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Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents