RECRUITING

Study of Radiotherapy and Pembrolizumab in People with Adrenocortical Carcinoma

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Safety and Immunological Effects of Pembrolizumab Plus Ablative Radiotherapy in Patients with Advanced Adrenocortical Carcinoma

Quick Facts

Study Start:2023-09-27

Study Completion:2026-09-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06066333

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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: 1. Patients \< 16 years of age: Lansky ≥ 50% 2. 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. * Female subjects of childbearing potential should have a negative serum pregnancy test within 72 hours prior to beginning treatment on study. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 10.6.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free of menses for \>1 year. * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.	* 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. * 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.

Inclusion Criteria

Exclusion Criteria

* 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:
1. Patients \< 16 years of age: Lansky ≥ 50%
2. 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.
* Female subjects of childbearing potential should have a negative serum pregnancy test within 72 hours prior to beginning treatment on study. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 10.6.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free of menses for \>1 year.
* Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

* 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.
* 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.

Contacts and Locations

Study Contact

Nitya Raj, MD

CONTACT

646-888-4849

rajn@mskcc.org

Diane Reidy-Lagunes, MD

CONTACT

646-888-4185

reidyd@mskcc.org

Principal Investigator

Nitya Raj, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk-Commack

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Nitya Raj, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-27

Study Completion Date2026-09-27

Study Record Updates

Study Start Date2023-09-27

Study Completion Date2026-09-27

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Adrenocortical Carcinoma
ACC
Metastatic Adrenocortical Carcinoma