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Study of Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer

Primary Purpose

Anaplastic Thyroid Cancer, Thyroid Cancer, BRAF Gene Mutation

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

About this trial

This is an interventional treatment trial for Anaplastic Thyroid Cancer focused on measuring Anaplastic Thyroid Cancer, Thyroid Cancer, Cemiplimab, BRAF-Mutant Anaplastic Thyroid Cancer, BRAF Mutation-Related Tumors, BRAF Gene Mutation, 19-464, Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

Inclusion Criteria:

  • Pathological (histologically or cytologically) proven diagnosis of BRAF-V600E mutant ATC (a diagnosis that is noted to be consistent with ATC is acceptable)
  • Either Metastatic disease or locoregional disease that is considered not resectable for cure
  • Ideally a surgeon should determine that the disease is not resectable for cure, but this can also be done by any investigator
  • Patients must have measurable disease according to RECIST 1.1 criteria, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as >/= 20 mm with conventional techniques or as >/= 10 mm with spiral CT scan, MRI, or calipers by clinical exam
  • Age >/= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status </= (or Karnofsky performance score >/= 60)
  • Able to swallow and retain orally administered medication
  • Patient must have normal organ and marrow function as defined below:

    • Absolute neutrophil count >/=1.5 x 10^9/L
    • Hemoglobin >/=8 g/dL
    • Platelets >/=100 x 10^9/L
    • Serum bilirubin </=1.5x institutional ULN (unless the patient has GIlbert's Disease, in which case total bilirubin </=3x institutional ULN)
    • AST and ALT </=2.5x institutional ULN (</=5x institutional ULN if there is liver metastasis)
    • Serum creatinine </=1.5mg/dL or calculated creatinined clearance (Cockcroft-Gault formula) >/=50 mL/min or 24-h urine creatinine clearance >/=50 mL/min
    • Left ventricular ejection fraction greater than or equal to instutional lower limit of normal (LLN) by echocardiogram or multigated acquisition (MUGA)
  • Negative pregnancy test (serum or urine) within 14 days of registration for women of childbearing potential. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry and for the duration of study participation. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and for 4 months after completion of trametinib administration
  • Must agree to allow 2-4 separate biopsies of any malignant lesion. For patients whose biopsies (initial) are deemed as unsafe or contraindicated, they will not be eligible.
  • Ability to understand and willingness to sign a written informed consent document. Note: Use of Legally Authorized Representative (LAR) is permitted

Exclusion Criteria:

  • Previous documentation or current evidence of treatment with dabrafenib and trametinib.

    ° Exception: (1) Patients who started dabrafenib and tranetinib for ATC at an institution outside of MSK are eligible or (2) with the consent of the PI (Sherman). However, this exception is limited to 8 subjects.

  • Active brain metastases, unless an exception is granted by the Principal Investigator.
  • Current interstitial lung disease or pneumonitis
  • Prior history of idelalisib therapy. Exceptions allowed with the consent of the principal investigator (Dr. Sherman)
  • History of retinal vein occlusion (RVO) or central serous retinopathy (CSR):

    ° History of RVO or CSR or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension)

  • History or current evidence of cardiovascular risk, including any of the following:

    • Left ventricular ejection fraction (LVEF) <LLN
    • A QT interval corrected for heart rate using the Bazett's formula of QTcB>/=480msec
    • Current evidence of clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for >30 days before enrollment are eligible)
    • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months before treatment
  • Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection, which will be allowed)

HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with trametinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

  • Uncontrolled intercurrent illness that would limit compliance with study requirement.
  • Inability to receive immunotherapy for the following reasons:

    • Any prior grade >/=3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent or any unresolved irAE grade >1
    • Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Exceptions allowed with the consent of the principal investigator (Dr. Sherman)
    • Active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
    • History of primary immunodeficiency
    • History of allogeneic organ transplant
    • Known history of previous clinical diagnosis of active tuberculosis (this does not include a history of being PPD positive)

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BRAF-mutant ATC

Arm Description

Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer

Outcomes

Primary Outcome Measures

Overall Response Rate per RECIST 1.1 Criteria
Response and progression will be evaluated by using criteria proposed in RECIST 1.1.

Secondary Outcome Measures

Full Information

First Posted
January 21, 2020
Last Updated
June 29, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04238624
Brief Title
Study of Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer
Official Title
A Pilot Study of the Addition of Cemiplimab, an Antibody to PD-1, to the Treatment of Subjects With BRAF-Mutant Anaplastic Thyroid Cancer Who Are No Longer Responding to Dabrafenib and Trametinib
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2020 (Actual)
Primary Completion Date
June 20, 2024 (Anticipated)
Study Completion Date
June 20, 2024 (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
This study is being done to see if adding the study drug, cemiplimab, to the standard therapy with dabrafenib and trametinib is an effective treatment against anaplastic thyroid cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaplastic Thyroid Cancer, Thyroid Cancer, BRAF Gene Mutation, BRAF Mutation-Related Tumors
Keywords
Anaplastic Thyroid Cancer, Thyroid Cancer, Cemiplimab, BRAF-Mutant Anaplastic Thyroid Cancer, BRAF Mutation-Related Tumors, BRAF Gene Mutation, 19-464, 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
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BRAF-mutant ATC
Arm Type
Experimental
Arm Description
Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer
Intervention Type
Drug
Intervention Name(s)
Dabrafenib
Intervention Description
Participants will receive dabrafenib 150 mg orally twice a day
Intervention Type
Drug
Intervention Name(s)
Trametinib
Intervention Description
Participants will receive trametinib 2 mg orally once a day
Primary Outcome Measure Information:
Title
Overall Response Rate per RECIST 1.1 Criteria
Description
Response and progression will be evaluated by using criteria proposed in RECIST 1.1.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathological (histologically or cytologically) proven diagnosis of BRAF-V600E mutant ATC (a diagnosis that is noted to be consistent with ATC is acceptable) Either Metastatic disease or locoregional disease that is considered not resectable for cure Ideally a surgeon should determine that the disease is not resectable for cure, but this can also be done by any investigator Patients must have measurable disease according to RECIST 1.1 criteria, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as >/= 20 mm with conventional techniques or as >/= 10 mm with spiral CT scan, MRI, or calipers by clinical exam Age >/= 18 years Eastern Cooperative Oncology Group (ECOG) performance status </= (or Karnofsky performance score >/= 60) Able to swallow and retain orally administered medication Patient must have normal organ and marrow function as defined below: Absolute neutrophil count >/=1.5 x 10^9/L Hemoglobin >/=8 g/dL Platelets >/=100 x 10^9/L Serum bilirubin </=1.5x institutional ULN (unless the patient has GIlbert's Disease, in which case total bilirubin </=3x institutional ULN) AST and ALT </=2.5x institutional ULN (</=5x institutional ULN if there is liver metastasis) Serum creatinine </=1.5mg/dL or calculated creatinined clearance (Cockcroft-Gault formula) >/=50 mL/min or 24-h urine creatinine clearance >/=50 mL/min Left ventricular ejection fraction greater than or equal to instutional lower limit of normal (LLN) by echocardiogram or multigated acquisition (MUGA) Negative pregnancy test (serum or urine) within 14 days of registration for women of childbearing potential. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry and for the duration of study participation. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and for 4 months after completion of trametinib administration Must agree to allow 2-4 separate biopsies of any malignant lesion. For patients whose biopsies (initial) are deemed as unsafe or contraindicated, they will not be eligible. Ability to understand and willingness to sign a written informed consent document. Note: Use of Legally Authorized Representative (LAR) is permitted Exclusion Criteria: Previous documentation or current evidence of treatment with dabrafenib and trametinib. ° Exception: (1) Patients who started dabrafenib and tranetinib for ATC at an institution outside of MSK are eligible or (2) with the consent of the PI (Sherman). However, this exception is limited to 8 subjects. Active brain metastases, unless an exception is granted by the Principal Investigator. Current interstitial lung disease or pneumonitis Prior history of idelalisib therapy. Exceptions allowed with the consent of the principal investigator (Dr. Sherman) History of retinal vein occlusion (RVO) or central serous retinopathy (CSR): ° History of RVO or CSR or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension) History or current evidence of cardiovascular risk, including any of the following: Left ventricular ejection fraction (LVEF) <LLN A QT interval corrected for heart rate using the Bazett's formula of QTcB>/=480msec Current evidence of clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for >30 days before enrollment are eligible) History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months before treatment Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection, which will be allowed) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with trametinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy Uncontrolled intercurrent illness that would limit compliance with study requirement. Inability to receive immunotherapy for the following reasons: Any prior grade >/=3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent or any unresolved irAE grade >1 Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Exceptions allowed with the consent of the principal investigator (Dr. Sherman) Active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) History of primary immunodeficiency History of allogeneic organ transplant Known history of previous clinical diagnosis of active tuberculosis (this does not include a history of being PPD positive)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eric Sherman, MD
Phone
614-888-4234
Email
shermane@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Davic Pfister, MD
Phone
646-888-4237
Email
pfisterd@mskcc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Sherman, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (Limited 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
Eric Sherman, MD
Phone
646-888-4234
Facility Name
Memorial Sloan Kettering Monmouth (Limited 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
Eric Sherman, MD
Phone
646-888-4234
Facility Name
Memorial Sloan Kettering Bergen (Limited 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
Eric Sherman, MD
Phone
646-888-4234
Facility Name
Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
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
Eric Sherman, MD
Phone
646-888-4234
Facility Name
Memorial Sloan Kettering Westchester (Limited 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
Eric Sherman, MD
Phone
646-888-4234
Facility Name
Memorial Sloan Kettering Cancer Center
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
Eric Sherman, MD
Phone
614-888-4234
Facility Name
Memorial Sloan Kettering Nassau (Limited 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
Eric Sherman, MD
Phone
646-888-4234

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 Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer

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