Pembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer

Running, not enrolling · Phase 2

Conditions studied: Thyroid Gland Anaplastic Carcinoma, Thyroid Gland Squamous Cell Carcinoma

In brief

This phase II trial studies the effect of pembrolizumab, dabrafenib, and trametinib before surgery in treating patients with BRAF V600E-mutated anaplastic thyroid cancer. BRAF V600E is a specific mutation (change) in the BRAF gene, which makes a protein that is involved in sending signals in cells and in cell growth. It may increase the growth and spread of tumor cells. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab, dabrafenib, and trametinib may help to control BRAF V600E-mutated anaplastic thyroid cancer when given before surgery.

Key facts

Study ID: NCT04675710
Run by: M.D. Anderson Cancer Center
People needed: 30
Starts: 2021-06-24
Expected to finish: 2026-10-30
Last updated by the study team: 2026-02-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma. Diagnosis may include consistent with or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present
Must have a BRAFV600E mutation-positive tumor, as determined by BRAF V600E immunohistochemistry on tumor tissue, genetic/molecular testing of tumor, or cell free (cf)NDA liquid biopsy
Have measurable disease based on RECIST 1.1
Total bilirubin =< 1.5 x upper limit of normal (ULN). Total bilirubin =< 3 x ULN for patients with Gilbert's syndrome
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN, (5 x ULN for patients with concurrent liver metastases)
Serum creatinine =< within 1.5 x ULN
Absolute neutrophil count (ANC) >= 1.0 x 10\^9/L
Platelets >= 100 x 10\^9/L
Hemoglobin >= 9.0 g/dL or 5.6 mmol/L
International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulant
Subjects must be willing to ultimately undergo surgery if their tumor becomes surgically resectable. For MD Anderson site only, subjects must be willing to undergo tumor biopsy after the run-in with DT, unless in the opinion of the treating physician, a biopsy is not feasible or safe. Research subjects retain the right to refuse any research interventions.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
A male participant must agree to use a contraception of this protocol during the treatment period and for at least 8 months after the last dose of study treatment and refrain from donating sperm during this period
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR
A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment

You may not qualify if…

Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) class II
Untreated brain metastases
Prior chemotherapy within < 1 week prior to study day 1 or patients who have not recovered (i.e., =< grade 2) from adverse events due to a previously administered agent, except for patients who have been on dabrafenib/trametinib (DT) according to the standard run-in outlined in the trial schema
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
History of human immunodeficiency virus (HIV) or active hepatitis B (chronic or acute) or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. However, patients with past or resolved hepatitis B virus (HBV) should be monitored for reactivation by a specialist. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Note: no testing for HIV, hepatitis B and hepatitis C is required unless mandated by local heath authority
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive beta-human chorionic gonadotropin [beta-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG [or hCG]). A women of childbirth potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to the first infusion will be excluded. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
More than 42 days of DT therapy prior to enrollment
A known history of retinal vein occlusion (RVO), central serous retinopathy (CSR), uncontrolled glaucoma or ocular hypertension

Where it is running

Stanford School of Medicine — Stanford, California, United States
University of Michigan Rogel Cancer Center — Ann Arbor, Michigan, United States
Mayo Clinic — Rochester, Minnesota, United States
Cleveland Clinic Taussig Cancer Institute — Cleveland, Ohio, United States
M D Anderson Cancer Center — Houston, Texas, United States
Huntsman Cancer Institute at the University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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