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A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma | Clinical Trials | Clareo Health

TERMINATEDPHASE2

A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma

NCT05634577•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

To learn if adding pembrolizumab to mitotane can help to control ACC. The safety of this drug combination will also be studied.

Detailed Description

Primary Objective(s), Hypothesis(es), and Endpoint(s): (1) Objective: Assess the clinical efficacy of the combined use of MT with PEM in patients with advanced ACC. Hypothesis: We hypothesize that adding PEM will enhance the clinical efficacy of MT. This additive/synergistic effect could be related to the intrinsic adrenolytic activity of MT that could lead to antigens exposures to immune cells. Furthermore, the cortisol lowering effect of mitotane is expected to alter the tumor microenvironment leading to a change the milieu of the tumor infiltrating immune cells to make ACC more susceptible to PEM. Also, cortisol lowering can reduce lymphocytes inhibition and enhances the efficacy of PEM. Primary Endpoint: Overall response rate (ORR) assessed objectively using RECIST 1.1 criteria defined as the percentage of patients who have a partial or complete response to the combined treatment of MT plus PEM Secondary Objective(s), Hypothesis(es), and Endpoint(s): (1) Objective: Evaluate the safety and efficacy of the combined use of MT plus PEM in patients with advanced ACC. Hypothesis: The optimal MT plasma levels have not been established prospectively in metastatic ACC. We hypothesize that mitotane level of 14-20 mg/L is associated with oncological responses, but we also anticipate that the combined use of PEM MT could be associated with responses at lower levels of MT which might be associated with more favorable AE profile of MT. Secondary Endpoints: 1. Overall survival (OS), defined as the time from combination therapy to death from any cause. 2. Progression Free Survival (PFS), defined as the time from the start of combination therapy phase to disease progression or death from any cause. 3. Explore the association between MT level and response to therapy 4. Safety assessment by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0 Exploratory Objective(s): (1) Objective: Correlate safety and efficacy data with steroid profile, immune markers and MT levels. 1. Obtain optional tumor biopsy prior to, during, and after treatment with MT/PEM combination to study immune markers such as infiltrating tumor lymphocytes, and other immune markers during therapy. 2. Study the changes in circulating markers (MT level, immune cytokines, steroid profile) in blood samples obtained prior to, during, and after treatment with MT/PEM combination

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Participants are eligible to be included in the study only if all of the following criteria apply:
•1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of ACC will be enrolled in this study.
•2. Male participants:
•A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and an additional 180 days after the last dose of study treatment and refrain from donating sperm during this period.
•3. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
•1. a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
•2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period plus 180 days after the last dose of study treatment.
•4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
•5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
•6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 10 days prior to the first dose of MT therapy.
+29 more criteria

Exclusion Criteria

•Participants are excluded from the study if any of the following criteria apply:
•1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to pembrolizumab treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
•2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
•3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks
•4. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
•5. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
•6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
•7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent at the time of screening) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Higher dose of steroid may be permitted as replacement doses while on mitotane therapy to follow acceptable standards of care while on mitotane Known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
•8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
•9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
+12 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

March 23, 2023

Primary Completion Date

July 10, 2024

Completion Date

July 10, 2024

Last Updated

June 19, 2025

Enrollment

ACTUAL participants

Conditions

Adrenocortical Carcinoma

Interventions

Mitotane

DRUG

Pembrolizumab

DRUG

Familial Investigations of Childhood Cancer Predisposition

NCT03050268

Acute LeukemiaAdenomatous Polyposis+44 more

View study

RECRUITING

German Adrenocortical Carcinoma Registry

NCT00453674

Adrenocortical Carcinoma

View study

RECRUITINGPHASE2

Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: June 19, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma

Inclusion Criteria

Exclusion Criteria

Familial Investigations of Childhood Cancer Predisposition

German Adrenocortical Carcinoma Registry

Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.

Evaluation of Side Effects of Mitotane

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