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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04238624
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : January 23, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Anaplastic Thyroid Cancer Thyroid Cancer BRAF Gene Mutation BRAF Mutation-Related Tumors Drug: Dabrafenib Drug: Trametinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 20, 2020
Estimated Primary Completion Date : June 20, 2022
Estimated Study Completion Date : June 20, 2022


Arm Intervention/treatment
Experimental: BRAF-mutant ATC
Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer
Drug: Dabrafenib
Participants will receive dabrafenib 150 mg orally twice a day

Drug: Trametinib
Participants will receive trametinib 2 mg orally once a day




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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: Patients who started dabrafenib and tranetinib for ATC at an institution outside of MSK are eligible. However, this exception is limited to 6 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 or current evidence or risk 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)
    • Visible retinal pathologic abnormality as assessed by ophthalmic exam that is considered a high risk factor for RVO or CSR, such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure >21 mm Hg.
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04238624


Contacts
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Contact: Eric Sherman, MD 614-888-4234 shermane@mskcc.org
Contact: Davic Pfister, MD 646-888-4237 pfisterd@mskcc.org

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eric Sherman, MD    614-888-4234      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Eric Sherman, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04238624    
Other Study ID Numbers: 19-464
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: January 23, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
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
Additional relevant MeSH terms:
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Thyroid Neoplasms
Thyroid Carcinoma, Anaplastic
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Trametinib
Dabrafenib
Cemiplimab
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological