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

June 29, 2023 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 646-888-4234
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 646-888-4234
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 646-888-4234
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 646-888-4234
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 646-888-4234
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 614-888-4234
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau (Limited protocol activities)
        • Contact:
          • Eric Sherman, MD
          • Phone Number: 646-888-4234

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.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BRAF-mutant ATC
Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer
Participants will receive dabrafenib 150 mg orally twice a day
Participants will receive trametinib 2 mg orally once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate per RECIST 1.1 Criteria
Time Frame: 2 years
Response and progression will be evaluated by using criteria proposed in RECIST 1.1.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Eric Sherman, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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 Major Dates

Study Start (Actual)

January 20, 2020

Primary Completion (Estimated)

June 20, 2024

Study Completion (Estimated)

June 20, 2024

Study Registration Dates

First Submitted

January 21, 2020

First Submitted That Met QC Criteria

January 21, 2020

First Posted (Actual)

January 23, 2020

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 29, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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