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

NCT01947023 | Active Not Recruiting Phase 1

• 5 other identifiers: NCI-2013-0174813-0619354P30CA008748U01CA069856
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Thyroid Gland Carcinoma; Unresectable Thyroid Gland Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of lapatinib, in combination with the established dose of dabrafenib

  Will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity MTD is defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity.

  First 42 days of treatment

Secondary Outcomes (2)

• Mean percent change in the post-treatment tissues relative to pre-treatment tissues for the phosphorylated protein targets examined

  Baseline to day 7 of cycle 1

• Mean percentage change in transcript levels in the post-treatment tissues relative to pre-treatment tissues for several genes analyzed by reverse-transcriptase-polymerase chain reaction

  Baseline to day 7 of cycle 1

Study Arms (1)

Treatment (lapatinib, dabrafenib)

EXPERIMENTAL

Patients receive dabrafenib PO BID on days 1-28 of each cycle. After two weeks of single agent dabrafenib, patients also start receiving lapatinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo tumor biopsy, blood sample collection, ECHO or MUGA, as well as PET, CT, and/or MRI during screening and on study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dabrafenib; Drug: Dabrafenib Mesylate; Procedure: Echocardiography Test; Drug: Lapatinib; Drug: Lapatinib Ditosylate; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography

Interventions

Dabrafenib DRUG

Given PO

Also known as: BRAF Inhibitor GSK2118436, GSK 2118436, GSK 2118436A, GSK-2118436, GSK-2118436A, GSK2118436, GSK2118436A

Treatment (lapatinib, dabrafenib)

Dabrafenib Mesylate DRUG

Given PO

Also known as: Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar

Treatment (lapatinib, dabrafenib)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (lapatinib, dabrafenib)

Lapatinib DRUG

Given PO

Also known as: GSK572016, GW 2016, GW 572016, GW-572016, GW2016, GW572016

Treatment (lapatinib, dabrafenib)

Lapatinib Ditosylate DRUG

Given PO

Also known as: Tykerb

Treatment (lapatinib, dabrafenib)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (lapatinib, dabrafenib)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (lapatinib, dabrafenib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (lapatinib, dabrafenib)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (lapatinib, dabrafenib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (lapatinib, dabrafenib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (lapatinib, dabrafenib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Biopsy; Specimen Handling; dabrafenib; Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Eric J Sherman

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2013
• First Posted: September 20, 2013
• Study Start: September 27, 2013
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Locations

US (1)