Clinical Trials /

Study of Relacorilant in Combination With Pembrolizumab for Patients With Adrenocortical Carcinoma With Excess Glucocorticoid Production

NCT04373265

Description:

This study will investigate the safety and efficacy of Relacorilant in combination with Pembrolizumab for Patients with Adrenocortical Carcinoma with Excess Glucocorticoid Production.

Related Conditions:
  • Adrenal Cortex Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CORT125134-551
  • NCT ID: NCT04373265

Conditions

  • Adrenocortical Carcinoma

Interventions

DrugSynonymsArms
RelacorilantCORT125134Relacorilant in Combination with Pembrolizumab
PembrolizumabKeytrudaRelacorilant in Combination with Pembrolizumab

Purpose

This study will investigate the safety and efficacy of Relacorilant in combination with Pembrolizumab for Patients with Adrenocortical Carcinoma with Excess Glucocorticoid Production.

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) with
      glucocorticoid (GC) excess.

      Eligible patients are those with advanced ACC associated with GC excess.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Relacorilant in Combination with PembrolizumabExperimentalRelacorilant dose escalation starting with 100 mg once daily in Cycle 1, followed by 200 mg once daily in Cycle 2, followed by 300 mg once daily in Cycle 3, followed by 400 mg (or highest tolerated dose) once daily in subsequent cycles up to 24 months treatment. The relacorilant dose can be reduced if not tolerated and subsequently increased if tolerated. Pembrolizumab 200-mg IV infusion on Day 1 of each cycle. Cycle duration is 3 weeks.
  • Relacorilant
  • Pembrolizumab

Eligibility 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.

          -  Tumor accessible for biopsy and consent to biopsies.

          -  Documented GC excess.

          -  If received mitotane, have a mitotane level <4mg/L at screening. 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
             Cycle 1 Day -3 Visits (before the patient can receive study treatment).

        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.

          -  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 (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)

          -  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. Systemic (oral or injectable) regular use, or prescription topical
                  glucocorticoids within 28 days. Short courses (≤5 days) for noncancer-related
                  reasons are allowed if clinically required (such as prophylaxis for CT).

               4. Mifepristone or other GR antagonists within 21 days

               5. Adrenostatic medications (e.g., ketoconazole, metyrapone, or fluconazole within
                  14 days; or etomidate within 7 days)

          -  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, nonmuscle 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
                  6 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Evaluate the percentage of patients with measurable disease at baseline who achieve confirmed complete response (CR) or partial response (PR) per RECIST v1.1

Secondary Outcome Measures

Measure:Non-Progression Rate (NPR)
Time Frame:27 weeks from enrollment
Safety Issue:
Description:Evaluate the non-progression rate (NPR) per RECIST v1.1
Measure: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
Safety Issue:
Description:To evaluate progression-free survival (PFS) per RECIST v1.1
Measure:Overall Survival (OS)
Time Frame:From date of first treatment, until the date of death from any cause, up to month 24
Safety Issue:
Description:To evaluate overall survival (OS)
Measure: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
Safety Issue:
Description:To evaluate the duration of response (DOR) per RECIST v1.1
Measure: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
Safety Issue:
Description:To assess the effect of relacorilant in combination with pembrolizumab on the clinical manifestations of cortisol excess (e.g. hypertension and diabetes mellitus)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Corcept Therapeutics

Trial 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

Last Updated

August 28, 2020