Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

NCT06066333 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 23-272
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to determine whether pembrolizumab given after standard ablative Radiotherapy is a safe treatment that causes few or mild side effects in people with advanced Adrenocortical Carcinoma.

Conditions

Adrenocortical Carcinoma; ACC; Metastatic Adrenocortical Carcinoma

Keywords

Adrenocortical Carcinoma; ACC; Metastatic Adrenocortical Carcinoma; Metastatic ACC; Metastatic ACC with symptomatic liver metastases; 23-272; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Number of participants evaluated for AEs

  The primary objective of this pilot study is to evaluate the safety of treatment with ablative Radiotherapy/RT followed by pembrolizumab in patients with advanced Adrenocortical Carcinoma/ACC by evaluating treatment related adverse events. AEs will be recorded according to "Common Terminology Criteria for Adverse Events" v5.0 (CTCAE).

  up to 1 year

Study Arms (1)

Participants with Adrenocortical Carcinoma

EXPERIMENTAL

Participants with histologically proven metastatic Adrenocortical Carcinoma/ACC with both intra-hepatic and extra-hepatic sites of disease.

Radiation: Ablative Radiotherapy; Drug: Pembrolizumab

Interventions

Ablative Radiotherapy RADIATION

All participants will first undergo ablative RT

Also known as: Ablative RT

Participants with Adrenocortical Carcinoma

Pembrolizumab DRUG

After completion of ablative RT, all subjects may begin pembrolizumab treatment

Participants with Adrenocortical Carcinoma

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 15 years of age on day of signing informed consent.
• Have histologically- or cytologically- confirmed metastatic ACC with symptomatic liver metastases.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
• Adequate performance status:
• Patients \< 16 years of age: Lansky ≥ 50%
• Patients ≥ 16 years of age: Karnofsky ≥ 50%
• Have measurable disease based on RECIST v1.1.
• Have radiologic documentation of extrahepatic tumor, defined as extrahepatic metastases.
• Consent for use of archived tissue for research purposes. Archival tissue (1 block or 20 unstained slides) will be requested, when available.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 28 days of treatment initiation.
• Table 1: Adequate Organ Function Laboratory Value
• Hematological Absolute neutrophil count (ANC) ≥1,500 / mcL Platelets ≥100,000 / mcL
• Renal Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• \*Creatinine clearance should be calculated per institutional standard.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to study Day 1 (the first day of ablative RT).
• Has undergone radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields (to include Y90).
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study Day 1. The use of physiologic doses of corticosteroids for adrenal and pituitary insufficiency is not considered a form of systemic steroid therapy and would not exclude a subject from the study.
• Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. The use of non-immunotherapy monoclonal antibodies (such as dupilumab (for eczema), omalizumab (for urticaria), benralizumab (for asthma)) would not exclude a subject from the study.
• Has had prior chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify for the study.
• If subject underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to beginning treatment on study and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for brain metastases for at least 7 days prior to study Day 1. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. Subjects that have adrenal or pituitary insufficiency that require physiologic corticosteroid replacement therapy would not be excluded from the study. Subjects who are on mitotane for control of hormonal symptoms for their disease at the time of eligibility assessment can continue on mitotane during the course of the study.
• Has evidence of interstitial lung disease or history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 11. Has an active infection requiring systemic therapy. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to study Day 1. Administration of killed vaccine is allowed.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk-Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

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

Study Officials

• Nitya Raj, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nitya Raj, MD

CONTACT

646-888-4849; rajn@mskcc.org

Rohit Thummalapalli, MD

CONTACT

646-888-4494; thummalr@mskcc.org

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: September 27, 2023
• First Posted: October 4, 2023
• Study Start: September 27, 2023
• Primary Completion (Estimated): September 27, 2026
• Study Completion (Estimated): September 27, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)