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

NCT04373265 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CORT125134-551
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 6

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).

Conditions

Adrenocortical Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicity (DLT)

  Evaluate the percentage of patients with a dose-limiting toxicity

  Up to 12 weeks

Secondary Outcomes (4)

• Non-Progression Rate (NPR)

  24 weeks from enrollment

• Progression-Free Survival (PFS)

  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

  Up to 37 days post-treatment

• Plasma Concentrations of Relacorilant in Combination with Pembrolizumab in Patients with Advanced ACC and Glucocorticoid Excess

  Up to 24 months

Study Arms (1)

Relacorilant in Combination with Pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Interventions

Relacorilant DRUG

Relacorilant, 100 mg soft gel capsules orally once daily

Also known as: CORT125134

Relacorilant in Combination with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 400 mg infusion every 6 weeks

Also known as: Keytruda

Relacorilant in Combination with Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Any investigational product, systemic anticancer therapy, or radiation therapy within 21 days
• Antibodies or anticancer vaccines within 60 days
• Mifepristone or other GR antagonists within 5 half-lives of these medications
• 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.

Sponsors & Collaborators

• Corcept Therapeutics: lead

Study Sites (6)

Site #150, Stanford Cancer Center

Stanford, California, 94305, United States

Location

Site #007, Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Site #074, University of Michigan Medical School

Ann Arbor, Michigan, 48109, United States

Location

Site #030 Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Site #051, Memorial Hospital

New York, New York, 10022, United States

Location

Site #183, The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Hypertension; Hyperglycemia; Diabetes Mellitus, Type 2; Glucose Intolerance; Cushing Syndrome; ACTH Syndrome, Ectopic; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Pathologic Processes

Interventions

relacorilant; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andreas G Moraitis, MD

  Corcept Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2020
• First Posted: May 4, 2020
• Study Start: September 30, 2020
• Primary Completion: October 17, 2023
• Study Completion: January 12, 2024
• Last Updated: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)