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

NCT05634577 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2022-0705NCI-2022-10009
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Adrenocortical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Assessment of tumor reduction by RECIST1.1 criteria

  From time of active itervention (Combination therapy)

Secondary Outcomes (3)

• Overall Survival

  Overall survival (OS), defined as the time from combination therapy to death from any cause.

• Progression Free Survival

  Progression Free Survival (PFS), defined as the time from the start of combination therapy phase to disease progression or death from any cause.

• Side Effects and Relationship Between Response and Drug Level

  Explore the association between MT level and response to therapy Safety assessment by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0

Study Arms (1)

Lead-in Phase

EXPERIMENTAL

Participants will first have a Lead-in Phase in which participants receive only mitotane. This will be 4 weeks long in most participants. Participants will then begin receiving pembrolizumab.

Drug: Mitotane; Drug: Pembrolizumab

Interventions

Mitotane DRUG

Given by PO

Lead-in Phase

Pembrolizumab DRUG

Given by vein (IV)

Lead-in Phase

Eligibility Criteria

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

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• 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.
• 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.
• 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:
• a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• 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.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• 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.
• 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.
• Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 10 days prior to the start of study intervention.
• The study will accept therapy naïve patients with metastatic ACC, patients who failed one prior line of therapy not including immunotherapy, patients who started MT within 4 weeks for metastatic disease, and patients who developed metastases while on adjuvant mitotane therapy. Patients who failed platinum-based chemotherapy combined with MT may be eligible to join the study at the discretion of the PI if their treatment ended \> 6 months before consenting for this study or if did not achieve therapeutic MT levels during prior treatment (MT level ≥ 14 mg/L).
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen in the 28 days immediately preceding initiation of study treatment
• Criteria for known Hepatitis B and C positive subjects
• Hepatitis B and C screening tests are not required unless:

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• 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.
• 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).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks
• 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.
• 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.
• 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.
• 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.
• 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.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection
• Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Mitotane; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Mouhammed Habra, MD
• Organization: M D Anderson Cancer Center

mahabra@mdanderson.org

713-792-2841

Study Officials

• Mouhammed Habra, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 2, 2022
• Study Start: March 23, 2023
• Primary Completion: July 10, 2024
• Study Completion: July 10, 2024
• Last Updated: June 19, 2025
• Results First Posted: June 19, 2025

Record last verified: 2025-06

Locations

US (1)