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

• ClinicalTrials.gov Identifier: NCT04373265
• Recruitment Status: Recruiting
• First Posted: May 4, 2020
• Last Update Posted: February 25, 2022
• Sponsor: Corcept Therapeutics
• Information provided by (Responsible Party): Corcept Therapeutics

Study Description

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.

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Corcept Therapeutics; 650-327-3270; clinicalstudies@corcept.com

Contact: Corcept Therapeutics; 650-327-3270; study551@corcept.com

Locations

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

Investigators

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

More Information

• Responsible Party: Corcept Therapeutics
• ClinicalTrials.gov Identifier: NCT04373265
• Other Study ID Numbers: CORT125134-551
• First Posted: May 4, 2020
• Last Update Posted: February 25, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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; Hypertension; Hyperglycemia; Type 2 Diabetes; Impaired Glucose Tolerance; Cortisol; Cushing; Cushing syndrome; Hypercortisolemia; Cushingoid; Moon Face; Dorsocervical Fat Pad; Pembrolizumab; Glucocorticoid Receptor; Relacorilant; GR Antagonist; Adrenal Corticotropic Hormone (ACTH); Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Pathologic Processes

Additional relevant MeSH terms:

Carcinoma; Adrenocortical Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents