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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04238624

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

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 :

Jan 20, 2020

Anticipated Primary Completion Date :

Jun 20, 2024

Anticipated Study Completion Date :

Jun 20, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall Response Rate per RECIST 1.1 Criteria [2 years]
Response and progression will be evaluated by using criteria proposed in RECIST 1.1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York	United States	11553