Clinical Trials /

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

NCT04238624

Description:

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.

Related Conditions:
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 19-464
  • NCT ID: NCT04238624

Conditions

  • Anaplastic Thyroid Cancer
  • Thyroid Cancer
  • BRAF Gene Mutation
  • BRAF Mutation-Related Tumors

Interventions

DrugSynonymsArms
DabrafenibBRAF-mutant ATC
TrametinibBRAF-mutant ATC

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
BRAF-mutant ATCExperimentalParticipants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer
  • Dabrafenib
  • Trametinib

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 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial 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

Last Updated

January 21, 2020