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Pharmacodynamic Study of Vemurafenib in the Neoadjuvant Setting in Patients With Locally Advanced Thyroid Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Thyroid Cancer

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Trial Information

Pharmacodynamic Study of Vemurafenib in the Neoadjuvant Setting in Patients With Locally Advanced Thyroid Cancer


Study Drug Administration and Groups:

If you are found to be eligible to take part in this study, you will take 4 tablets of
vemurafenib by mouth 2 times each day for 56 days. You should take each dose about 12 hours
apart. If you miss taking the drug at a scheduled time by more than 4 hours, you should
skip that dose and wait until the next dose.

After 56 days, the treatment you receive will depend on what group you are assigned to:

- If the disease has spread outside the neck, you will be in Group A.

- If the disease is able to be entirely removed through surgery, you will be in Group B.

- If the disease is unable to be operated on, you will be in Group C.

Study Visits:

At all visits, you will be asked about any side effects you may be having and about any
other drugs you may be taking.

At Day 28:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- You will have an EKG.

- Blood (about 1 tablespoon) will be drawn for routine tests.

Within 1 week before Day 56, you will have CT scans of the neck, chest, and abdomen to check
the status of the disease.

At Day 56, if you are in Group A or B, you will have surgery to remove the tumor. You will
sign a separate consent form that describes this surgery and its risks. If you are in Group
C, you will have a core biopsy. During the surgery/biopsy, blood (about 1 teaspoon) will
also be collected for biomarker testing.

Follow-Up:

Your follow-up after the surgery/biopsy will depend on which study group you are in.

Groups A and C:

If you are in Group A, you will stop taking the study drug for about 2-4 weeks after you
have surgery. If you are in Group C, you will not stop taking the study drug. Every 4
weeks (after you resume taking the study drug if you are in Group A, and after the biopsy if
you are in Group C):

- You will have a physical exam, including measurement of your vital signs and a skin
exam.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any other drugs you may be taking and about any side effects
you may be having.

- If you are in Group A, these tests will also be performed the day you start taking the
study drug again. You will also have an EKG.

Additionally, every 8 weeks (if you are in Group A or C), you will have CT scans of the
neck, chest, and abdomen to check the status of the disease. Blood (about 1 teaspoon) will
also be drawn for biomarker testing at the first of these visits.

About 1 year after the surgery/biopsy, you will return to clinic to check if the disease has
come back. At this visit, you will have a CT scan or ultrasound of the neck, and blood
(about 1 tablespoon) will be drawn for tests of your thyroid function.

If after 4 months the study doctor thinks it is in your best interest, you will only need to
have study visits every 8 weeks. You will still have blood (about 1 tablespoon) drawn for
routine tests at a local lab and you will be called by the study staff to check on you.
Each call will last about 5-10 minutes.

If you are in Group C, and if during follow-up the study doctor decides that the disease can
be operated on, you will be crossed over to Group A or B. You will have surgery and have
the follow-up visits described for that study group.

Group B:

If you are in Group B, you will have a follow-up visit about 2 weeks after surgery. The
following tests and procedures will be performed:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any other drugs you may be taking and about any side effects
you may be having.

You will have a second follow-up visit about 8 weeks after surgery. You will have a CT scan
of the neck to check the status of the disease. You will have the option of continuing to
receive vemurafenib if your doctor thinks it is in your best interest. If you do continue
on vemurafenib, you will follow the Group A follow-up schedule (above).

About 1 year after the surgery/biopsy, you will return to clinic to check if the disease has
come back. At this visit, you will have a CT scan or ultrasound of the neck, and blood
(about 1 tablespoon) will be drawn for tests of your thyroid function.

Length of Study:

If you are in Group A or C, you will continue to take the study drug for as long as the
study doctor thinks it is in your best interest. If you are in Group B, you will take the
study drug for 56 days and will no longer take it after surgery. You will no longer be able
to take the study drug if the disease gets worse, if intolerable side effects occur, or if
you are unable to follow study directions.

Your participation on the study will be over when you have completed the follow-up visits.

End-of-Study Visit/Call:

After you stop taking the study drug, you will have an end-of-study visit or phone call.
You will be asked about any other drugs you may be taking and about any side effects you may
have had. If you are called, the call will last about 5-10 minutes.

This is an investigational study. Vemurafenib is FDA approved and commercially available
for the treatment of late-stage melanoma. It is investigational to use this drug to treat
thyroid cancer.

Up to 22 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. 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.

2. Persistent or locally recurrent PTC with macroscopic lymph node involvement which
requires surgical resection.

3. 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.

4. BRAF V600E mutation detected in the primary tumor or the recurrent/persistent tumor.

5. Total bilirubin syndrome are excluded from this requirement. Aspartate transaminase (serum glutamic
oxaloacetic transaminase) / alanine transaminase (serum glutamic pyruvic
transaminase) (AST[SGOT]/ALT[SGPT]) concurrent liver metastases). Serum creatinine neutrophil count (ANC) >/= 1.0 * 10^9/L; platelets >/= 100 * 10^9/L

6. 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).

7. Ability to swallow pills.

8. Eastern Cooperative Oncology Group (ECOG) performance status
9. Age >/= 18

10. Ability to provide consent.

Exclusion Criteria:

1. 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.

2. Refractory nausea and vomiting, malabsorption, or significant bowel resection that
would preclude adequate absorption.

3. Known hepatitis B or C virus (HBV or HCV) infection.

4. 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

5. Untreated brain metastases.

6. Chemotherapy or targeted therapy within 14 days or 5 half-lives (whichever is longer)
prior to the start of study treatment.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percent Change in ERK (Extracellular-Signal-Regulated Kinase) Phosphorylation and Tumor Size

Outcome Description:

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.

Outcome Time Frame:

56 days

Safety Issue:

No

Principal Investigator

Maria E. Cabanillas, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2012-0471

NCT ID:

NCT01709292

Start Date:

November 2012

Completion Date:

Related Keywords:

  • Thyroid Cancer
  • Thyroid Cancer
  • ERK
  • Extracellular-signal-regulated kinase
  • Biomarkers
  • Papillary thyroid cancer
  • PTC
  • BRAF mutated
  • Vemurafenib
  • PLX4032
  • RO5185426
  • Zelboraf™
  • Thyroid Neoplasms
  • Thyroid Diseases

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030