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Protein Kinase Inhibitor

Dabrafenib + Lapatinib for Thyroid Cancer

Phase 1
Waitlist Available
Led By Eric J Sherman
Research Sponsored by National Cancer Institute (NCI)
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Fludeoxyglucose F 18 (FDG)-avid lesion (standard uptake variable maximum [SUVmax] >= 3) on a FDG-positron emission tomography (PET) scan
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)
Must not have
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 NYHA functional classification system, intra-cardiac defibrillators, abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study, history or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible, treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy
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
Timeline
Screening 3 weeks
Treatment Varies
Follow Up baseline to day 7 of cycle 1
Awards & highlights

Summary

This trial is testing the combination of lapatinib and dabrafenib in patients with hard-to-treat thyroid cancer. The drugs work by blocking proteins that help cancer cells grow. The goal is to find the best dose and observe any anti-tumor activity. Dabrafenib has shown antitumor activity in various cancers, including thyroid cancer, and lapatinib is a tyrosine kinase inhibitor used in breast cancer treatment.

Who is the study for?
This trial is for patients with thyroid cancer that's spread or can't be removed by surgery, and hasn't improved after standard treatments. Participants must have a specific BRAF V600E or V600K mutation in their tumor, good organ function, no recent cancer treatments, and an ability to swallow pills. Women who can have children need to use non-hormonal birth control during the study.
What is being tested?
The trial is testing the combination of two drugs: Dabrafenib and Lapatinib. These drugs are believed to block enzymes important for cancer cell growth. The study aims to find the best dose with acceptable side effects for patients whose thyroid cancer has not been controlled by other treatments.
What are the potential side effects?
Potential side effects include but are not limited to diarrhea, rash, fatigue, nausea and vomiting. There may also be liver issues like increased enzymes in blood tests or heart problems such as decreased heart function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My PET scan shows a highly active lesion with an SUVmax of 3 or more.
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My cancer does not absorb radioactive iodine well, as confirmed by a specialist.
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My cancer has spread, cannot be surgically removed, and standard treatments are not effective.
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I am mostly active and can care for myself.
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I can take pills and don't have major gut issues affecting drug absorption.
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My cancer is advanced, cannot be surgically removed, and standard treatments are not effective.
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My platelet count is at least 100,000 per microliter of blood.
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My liver tests are within the normal range required by the study.
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I am mostly able to care for myself and carry out daily activities.
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I have received more than 600 mCi of radioactive iodine in my lifetime.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have serious heart problems or uncontrolled high blood pressure.
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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.
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My cancer has never tested positive for RAS mutations.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~baseline to day 7 of cycle 1
This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to day 7 of cycle 1 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Maximum tolerated dose (MTD) of lapatinib, in combination with the established dose of dabrafenib
Secondary study objectives
Body tissue
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

Side effects data

From 2018 Phase 3 trial • 1286 Patients • NCT00073528
60%
Diarrhoea
34%
Rash
29%
Nausea
19%
Fatigue
17%
Arthralgia
15%
Vomiting
15%
Back pain
13%
Headache
13%
Dry skin
12%
Asthenia
12%
Decreased appetite
12%
Pruritus
11%
Cough
11%
Alopecia
10%
Pain in extremity
10%
Nail disorder
10%
Hot flush
9%
Dyspnoea
9%
Alanine aminotransferase increased
9%
Epistaxis
9%
Dyspepsia
8%
Anaemia
8%
Nasopharyngitis
8%
Aspartate aminotransferase increased
8%
Musculoskeletal pain
7%
Abdominal pain
7%
Constipation
7%
Dizziness
6%
Insomnia
6%
Abdominal pain upper
6%
Mucosal inflammation
6%
Pyrexia
6%
Acne
6%
Paronychia
5%
Stomatitis
5%
Upper respiratory tract infection
5%
Urinary tract infection
5%
Blood alkaline phosphatase increased
5%
Weight decreased
5%
Muscle spasms
5%
Musculoskeletal chest pain
5%
Erythema
4%
Bone pain
4%
Myalgia
4%
Oedema peripheral
3%
Ejection fraction decreased
1%
Left ventricular dysfunction
1%
Chest pain
1%
Erysipelas
1%
Dehydration
1%
Cellulitis
100%
80%
60%
40%
20%
0%
Study treatment Arm
Placebo + Letrozole 2.5 mg
Lapatinib 1500 mg + Letrozole 2.5 mg

Trial Design

1Treatment groups
Experimental Treatment
Group I: Treatment (lapatinib, dabrafenib)Experimental Treatment11 Interventions
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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Echocardiography
2013
Completed Phase 4
~11580
Lapatinib
2006
Completed Phase 3
~3530
Multigated Acquisition Scan
2015
Completed Phase 3
~270
Positron Emission Tomography
2011
Completed Phase 2
~2200
Biospecimen Collection
2004
Completed Phase 3
~2020
Computed Tomography
2017
Completed Phase 2
~2740
Lapatinib Ditosylate
2006
Completed Phase 3
~580
Magnetic Resonance Imaging
2017
Completed Phase 3
~1160
Biopsy
2014
Completed Phase 4
~1090
Dabrafenib Mesylate
2014
Completed Phase 2
~10
Dabrafenib
2011
Completed Phase 3
~3420

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Lapatinib and Dabrafenib are targeted therapies used in treating thyroid cancer by inhibiting specific pathways involved in tumor growth. Lapatinib blocks the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (ErbB2), as well as downstream signaling molecules like Erk-1, Erk-2, and AKT, which are crucial for cell proliferation. Dabrafenib specifically inhibits the BRAF V600E mutation, disrupting the MAPK/ERK pathway that promotes cancer cell growth. These treatments are important for thyroid cancer patients as they offer a targeted approach, potentially leading to more effective and personalized therapy options.
Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells.Thyroid cancer cell resistance to gefitinib depends on the constitutive oncogenic activation of the ERK pathway.

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,842 Previous Clinical Trials
41,002,979 Total Patients Enrolled
Eric J ShermanPrincipal InvestigatorMemorial Sloan Kettering Cancer Center
1 Previous Clinical Trials
123 Total Patients Enrolled
~0 spots leftby Dec 2024
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