Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer
Pharmacodynamic Study of Vemurafenib in the Neoadjuvant Setting in Patients With Locally Advanced Thyroid Cancer
2 other identifiers
interventional
24
1 country
1
Brief Summary
The goal of this clinical research study is to learn about how vemurafenib may affect certain biomarkers in patients with PTC. Biomarkers are in the blood/tissue and may be related to your reaction to the study drug. The safety of this drug will also be studied. Vemurafenib is designed to block the BRAF gene mutation. This mutation causes cancer and cancer growth. By blocking this mutation, the drug may kill the cancer cells with the mutation and/or stop the tumor from growing.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Nov 2012
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 25, 2012
CompletedFirst Posted
Study publicly available on registry
October 18, 2012
CompletedStudy Start
First participant enrolled
November 7, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2026
April 16, 2026
April 1, 2026
13.9 years
July 25, 2012
April 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percent Change in ERK (Extracellular-Signal-Regulated Kinase) Phosphorylation and Tumor Size
ERK phosphorylation and tumor size measured at baseline before first dose of Vemurafenib and again after 56 days of Vemurafenib. We will test whether correlation between percent change in ERK phosphorylation and percent change in tumor size is different from 0 with a t-test.
56 days
Secondary Outcomes (1)
Objective Response Rate
56 days
Study Arms (4)
Vemurafenib - (Presurgery)
EXPERIMENTALAll Groups: Vemurafenib 960 mg by mouth 2 times a day for 56 days prior to surgery (patients not planned for surgical resection will have a core biopsy at day 56 +/- 7 days).
Vemurafenib (Post Surgery) - Group A
EXPERIMENTALVemurafenib 960 mg by mouth two times a day 2 weeks post-surgery, or if patients have not sufficiently recovered at that point, as soon as their condition permits. Patients in Group A restaged 8 weeks after resuming drug. If patients in Group A demonstrate either stable or regressing disease, they will continue on vemurafenib with restaging occurring every 8 weeks until no longer benefitting from the drug.
Post Surgery - Group B
NO INTERVENTIONPost Surgery - Group B: Patients discontinue vemurafenib after surgery but will be restaged with CT neck 8 weeks after surgery.
Vemurafenib - Group C
EXPERIMENTALPatients not scheduled for surgical resection undergo a CT scan and core biopsy at day 56, Vemurafenib 960 mg by mouth twice a day unless there is evidence of progressive disease on day 56 CT scan. Patients evaluated for resectability after each CT scan is performed. If scheduled for resection, patient continues vemurafenib until surgery and follows same treatment schema as patients in Groups A and B.
Interventions
960 mg by mouth 2 times a day 56 days prior to surgery (patients not planned for surgical resection will have a core biopsy at day 56.
Group A: 960 mg by mouth twice a day 2 weeks post-surgery. Restaged 8 weeks after resuming drug. If patients demonstrate either stable or regressing disease, they will continue on vemurafenib with restaging occurring every 8 weeks until they are no longer benefitting from the drug. Group C: Patients not scheduled for surgical resection undergo a CT scan and core biopsy at day 56. Vemurafenib 960 mg by mouth twice a day, continued unless there is evidence of progressive disease on day 56 CT scan. Patients restaged every 8 weeks and continue vemurafenib until no longer benefitting from the drug. Patients evaluated for resectability after each CT scan is performed. If patient is scheduled for resection, then patient will continue vemurafenib until surgery and will follow the same treatment schema as patients in Groups A and B.
Patients who have had a complete surgical resection, and who do not have evidence of metastatic disease will discontinue vemurafenib after surgery. Patients restaged with CT neck 8 weeks after surgery.
Eligibility Criteria
You may qualify if:
- Primary papillary thyroid cancer (PTC), which appears to be stage T3 or T4 on imaging or with macroscopic lymph node involvement AND requires surgical resection.
- Persistent or locally recurrent PTC with macroscopic lymph node involvement which requires surgical resection.
- Patients deemed inoperable (no scheduled surgery) are eligible for this trial, as they could be surgical candidates after treatment with vemurafenib. Inoperable patients must be naïve to therapies targeting the MAPK pathway.
- BRAF V600E mutation detected in the primary tumor or the recurrent/persistent tumor.
- Total bilirubin \</= 1.5 x upper limit of normal (ULN). Patients with Gilbert's syndrome are excluded from this requirement. Aspartate transaminase (serum glutamic oxaloacetic transaminase) / alanine transaminase (serum glutamic pyruvic transaminase) (AST\[SGOT\]/ALT\[SGPT\]) \</= 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, HgB\>9 mg/dL
- Antiangiogenic therapy, specifically vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors, can interfere with wound healing and therefore will only be allowed if the agent has been discontinued for at least 14 days prior to day 1. Group C patients must be naïve to therapies which target mitogen-activated protein kinase (MAPK).
- Ability to swallow pills.
- Eastern Cooperative Oncology Group (ECOG) performance status \</= 2
- Age \>/= 18
- Ability to provide consent.
You may not qualify if:
- Histological diagnosis other than PTC. Patients with anaplastic tumors are not eligible. However, patients whose tumors contain areas of un-differentiated or dedifferentiated histology may enroll provided the original diagnosis was clearly PTC, and the tumor histology remains predominantly papillary at enrollment.
- Refractory nausea and vomiting, malabsorption, or significant bowel resection that would preclude adequate absorption.
- Known hepatitis B or C virus (HBV or HCV) infection, unless the patient has been cleared for chemotherapy from experts on viral hepatitis (infectious disease specialists or hepatologists).
- Pregnant or lactating women. All pre-menopausal women being screened must have a negative serum pregnancy test within 14 days prior to commencement of dosing. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for \>/= 1 year
- Untreated brain metastases.
- Chemotherapy or targeted therapy within 14 days or 5 half-lives (whichever is longer) prior to the start of study treatment.
- Patients with history of long QT syndrome, uncorrectable electrolyte abnormalities, or QTc\>500msec.
- History of significant cardiac disease or uncontrolled arrhythmias.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Genentech, Inc.collaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Maria E. Cabanillas, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2012
First Posted
October 18, 2012
Study Start
November 7, 2012
Primary Completion (Estimated)
September 30, 2026
Study Completion (Estimated)
September 30, 2026
Last Updated
April 16, 2026
Record last verified: 2026-04