Vemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01709292
First received: July 25, 2012
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Thyroid Cancer
Drug: Vemurafenib (All Groups)
Drug: Vemurafenib (Post Surgery) - Group A + C
Other: Post Surgery - Group B
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacodynamic Study of Vemurafenib in the Neoadjuvant Setting in Patients With Locally Advanced Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Percent Change in ERK (Extracellular-Signal-Regulated Kinase) Phosphorylation and Tumor Size [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    Objective response rate defined as proportion of patients who have had a partial response (PR) or complete response (CR) after initiation of therapy with Vemurafenib, using RECIST 1.1. All patients who complete baseline and day 56 scans evaluable for this endpoint.


Estimated Enrollment: 22
Study Start Date: November 2012
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vemurafenib - Presurgery
All 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).
Drug: Vemurafenib (All Groups)
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.
Other Names:
  • PLX4032
  • RO5185426
  • Zelboraf™
Drug: Vemurafenib (Post Surgery) - Group A + C

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.

Other Names:
  • PLX4032
  • RO5185426
  • Zelboraf™
Other: Post Surgery - Group 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.
Experimental: Vemurafenib (Post Surgery) - Group A
Vemurafenib 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.
Drug: Vemurafenib (Post Surgery) - Group A + C

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.

Other Names:
  • PLX4032
  • RO5185426
  • Zelboraf™
No Intervention: Post Surgery - Group B
Post Surgery - Group B: Patients discontinue vemurafenib after surgery but will be restaged with CT neck 8 weeks after surgery.
Experimental: Vemurafenib (Post Surgery) - 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 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.
Drug: Vemurafenib (Post Surgery) - Group A + C

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.

Other Names:
  • PLX4032
  • RO5185426
  • Zelboraf™

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 </= 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
  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 </= 2
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709292

Contacts
Contact: Madonna M Pool, MSN 713-792-9851

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech
Investigators
Principal Investigator: Maria E. Cabanillas, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01709292     History of Changes
Other Study ID Numbers: 2012-0471, NCI-2012-02171
Study First Received: July 25, 2012
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Thyroid Cancer
Papillary thyroid cancer
ERK
Extracellular-signal-regulated kinase
Biomarkers
PTC
BRAF mutated
Vemurafenib
PLX4032
RO5185426
Zelboraf™

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms

ClinicalTrials.gov processed this record on September 16, 2014