Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery

Running, not enrolling · Phase 1

Conditions studied: Metastatic Thyroid Gland Carcinoma, Unresectable Thyroid Gland Carcinoma

In brief

This phase I trial studies the side effects and best dose of lapatinib when given together with dabrafenib in treating patients with thyroid cancer that cannot be removed by surgery and has not responded to previous treatment (refractory). Dabrafenib selectively binds to and blocks the activity of v-raf murine sarcoma viral oncogene homolog B (BRAF), which may block the growth of tumor cells which contain a mutated BRAF gene. Lapatinib reversibly blocks the process in which a phosphate group is added to a molecule (phosphorylation) of the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (ErbB2), and the mitogen-activated protein kinase 3 (Erk-1) and mitogen-activated protein kinase 1(Erk-2) and protein kinase B (AKT) kinases. It also blocks cyclin D protein levels in human tumor cell lines. Dabrafenib and lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID

NCT01947023

Run by

National Cancer Institute (NCI)

People needed

23

Starts

2013-09-27

Expected to finish

2027-05-12

Last updated by the study team

2026-05-14

Who can join

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

You may qualify if…

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
• Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF V600E or V600K (c. 1799 T to A and c.1799_1800TG>AA) mutation that is not considered curable by surgery; confirmation will be done at Memorial Sloan Kettering (MSK); only tumors with a BRAFV600E or BRAFV600K mutation will be eligible for the clinical study; BRAF status will be assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; BRAF status may also be tested with any Food and Drug Administration (FDA)-approved test (such as Cobas 4800 BRAF V600 Mutation Test)
• The tumor is considered to be radioactive-iodine refractory by any of the following criteria:
• Total lifetime dose of radioactive iodine > 600 mCi
• Absent or insufficient radioactive iodine uptake in either all lesions or an index lesion which has never been resected or received external beam radiation therapy as documented on a radioactive iodine scan (insufficient uptake must be confirmed by either an endocrinologist or nuclear medicine physician)
• Progression of disease (by imaging or thyroglobulin) within 6 months of radioactive iodine treatment
• Fludeoxyglucose F 18 (FDG)-avid lesion (standard uptake variable maximum [SUVmax] >= 3) on a FDG-positron emission tomography (PET) scan
• No recent treatment for thyroid cancer as defined as:
• No radioactive iodine therapy is allowed if given < 3 months prior to initiation of this protocol therapy; a diagnostic study using < 10 mCi of radioactive iodine (RAI) is not considered radioactive iodine therapy
• No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol
• No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy
• Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of dabrafenib in combination with lapatinib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Karnofsky >= 60%
• Life expectancy of greater than 2 months
• Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Absolute neutrophil count (ANC) >= 1.2 x 10\^9/L, within 2 weeks of the first dose of study treatment
• Hemoglobin >= 9 g/dL, within 2 weeks of the first dose of study treatment
• Platelets >= 100 x 10\^9/L, within 2 weeks of the first dose of study treatment
• Bilirubin =< 1.5 x institutional upper limit of normal (ULN) except subjects with known Gilbert's syndrome, within 2 weeks of the first dose of study treatment
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN, within 2 weeks of the first dose of study treatment
• Blood creatinine =< 1.5 mg/dL (if blood creatinine is > 1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault method or using a 24 hour urine collection for creatinine; creatinine clearance must be > 50 mL/min), within 2 weeks of the first dose of study treatment
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with PT/INR/PTT established within the therapeutic range prior to randomization; subjects will be eligible if it is determined by a hematologist that the cause is not associated with clinical bleeding (e.g., deficiency of factor XII), within 2 weeks of the first dose of study treatment
• Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO), within 2 weeks of the first dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study treatment

You may not qualify if…

• Prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study
• Current use of a prohibited medication; patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list of these agents; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Prohibited: strong inducers of CYP3A or CYP2C8, since concentrations of dabrafenib may be decreased
• Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine)
• Anticonvulsant: carbamazepine, oxcarbazepine phenobarbital, phenytoin, s-mephenytoin
• Miscellaneous: bosentan, St. John's wort
• Prohibited: strong inhibitors of CYP3A or CYP2C8, since concentrations of dabrafenib may be increased
• Antibiotics: clarithromycin, telithromycin, troleandomycin
• Antidepressant: nefazodone
• Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole
• Hyperlipidemia: gemfibrozil
• Antiretroviral: ritonavir, saquinavir, atazanavir
• Miscellaneous: conivaptan
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia; in specific cases, will be allowed with permission from the principal investigator
• Human immunodeficiency virus (HIV)-positive patients on antiviral drugs and/or cluster of differentiation (CD)4 count is inadequate (< 500); if neither condition exists, HIV-positive patients are eligible
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• A history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the exception of cleared HBV and HCV infection, which will be allowed)
• Presence of an invasive malignancy other than the study indication under this trial within 3 years of study enrollment except for carcinoma in situ CIS, squamous cell carcinomas of the skin, or basal cell carcinoma of the skin; a diagnosis of an invasive malignancy within 3 years is allowed if both the cure rate is felt to be > 80% and there has been no evidence of disease in the past year
• Patients with a history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; Note: prospective RAS testing is not required; however if the results of previous RAS testing are known, they must be used in assessing eligibility
• Brain metastases that are symptomatic or requiring corticosteroids (except inhaled); subjects must also be off of enzyme-inducing anticonvulsants for > 4 weeks
• History or evidence of cardiovascular risks including any of the following:
• History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization
• History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• Intra-cardiac defibrillators

Where it is running

• Memorial Sloan Kettering Cancer Center — New York, New York, United States

Full record on ClinicalTrials.gov

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