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Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

Primary Purpose

Adrenocortical Carcinoma, ACC, Metastatic Adrenocortical Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ablative Radiotherapy
Pembrolizumab
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adrenocortical Carcinoma focused on measuring Adrenocortical Carcinoma, ACC, Metastatic Adrenocortical Carcinoma, Metastatic ACC, Metastatic ACC with symptomatic liver metastases, 23-272, Memorial Sloan Kettering Cancer Center

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Be willing and able to provide written informed consent for the trial. Be ≥ 18 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 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. Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 5 X ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: 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. 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.

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Suffolk-CommackRecruiting
  • Memorial Sloan Kettering Westchester (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (All Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participants with Adrenocortical Carcinoma

Arm Description

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Full Information

First Posted
September 27, 2023
Last Updated
September 27, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT06066333
Brief Title
Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma
Official Title
Safety and Immunological Effects of Ablative Radiotherapy Followed by Pembrolizumab in Patients With Advanced Adrenocortical Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2023 (Actual)
Primary Completion Date
September 27, 2026 (Anticipated)
Study Completion Date
September 27, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants with Adrenocortical Carcinoma
Arm Type
Experimental
Arm Description
Participants with histologically proven metastatic Adrenocortical Carcinoma/ACC with both intra-hepatic and extra-hepatic sites of disease.
Intervention Type
Radiation
Intervention Name(s)
Ablative Radiotherapy
Other Intervention Name(s)
Ablative RT
Intervention Description
All participants will first undergo ablative RT
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
After completion of ablative RT, all subjects may begin pembrolizumab treatment
Primary Outcome Measure Information:
Title
Number of participants evaluated for AEs
Description
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).
Time Frame
up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be willing and able to provide written informed consent for the trial. Be ≥ 18 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 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. Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 5 X ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 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. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nitya Raj, MD
Phone
646-888-4849
Email
rajn@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Diane Reidy-Lagunes, MD
Phone
646-888-4185
Email
reidyd@mskcc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849
Facility Name
Memorial Sloan Kettering Monmouth (All Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849
Facility Name
Memorial Sloan Kettering Bergen (All Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849
Facility Name
Memorial Sloan Kettering Suffolk-Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849
Facility Name
Memorial Sloan Kettering Westchester (All Protocol Activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849
Facility Name
Memorial Sloan Kettering Nassau (All Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nitya Raj, MD
Phone
646-888-4849

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma

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