Vemurafenib and Sorafenib in Advanced Cancer

This study is currently recruiting participants.
Verified December 2013 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01531361
First received: February 6, 2012
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of the combination of ZelborafTM (vemurafenib) with Nexavar® (sorafenib) or Xalkori® (crizotinib) that can be given to patients with advanced cancer. The safety of these drugs will also be studied.

Vemurafenib is designed to block a protein called BRAFV600E inside the cancer cells, which is involved in cancer cell growth.

Sorafenib is designed to block the function of important proteins in and outside of cancer cells. These proteins are involved in cancer cells growth and new blood vessel development.

Crizotinib is designed to block certain abnormal genes found in cancer cells. This may cause the cancer cells to die.


Condition Intervention Phase
Advanced Cancers
Drug: Vemurafenib
Drug: Sorafenib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Vemurafenib (BRAF Inhibitor) and Sorafenib (CRAF, BRAF, KIT, RET, VEGFR, PDGFR Inhibitor) in Patients With Advanced Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Vemurafenib and Sorafenib [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    If more than 33% of enrolled at any particular dose level develop dose limiting toxicity (DLT), treatment will continue at dose level immediately below. If not more than 33% of cohort develop DLT, this cohort will be considered the MTD.


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e., decrease in size by 10% or more, or a decrease in the tumor density, as measured by Hounsfield units (HU), by more than or equal to 15%.


Estimated Enrollment: 183
Study Start Date: February 2012
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vemurafenib + Sorafenib
Starting dose of Vemurafenib 240 mg by mouth twice a day for 28 day cycle. Starting dose of Sorafenib 200 mg by mouth twice a day for 28 day cycle. Expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.
Drug: Vemurafenib

Starting Dose: 240 mg by mouth twice a day for a 28 day cycle.

Expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Other Names:
  • PLX4032
  • R05185426
Drug: Sorafenib

Starting dose: 200 mg by mouth twice a day for a 28 day cycle.

Expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Other Names:
  • Nexavar
  • Bay 43-9006

  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. Patients with advanced or metastatic cancers and BRAF mutations that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months. Patients with BRAF mutation in cell free DNA (tested in CLIA lab) are also eligible.
  2. Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment provided that radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks from the last dose (whichever comes first). Patients previously treated with vemurafenib monotherapy do not have to stop medication before they start on the protocol.
  3. ECOG performance status </= 2
  4. Patients must be >/= 18 years of age.
  5. Patients must have adequate organ and marrow function defined as: absolute neutrophil count (ANC) >/= 1,000/mL, platelets >/=75,000/mL; creatinine </= 2 X ULN; total bilirubin </= 2 X ULN; ALT (SGPT) and/or AST (SGOT) </= 5 X ULN Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT (SGPT) </= 8 X ULN.
  6. Dermatology evaluation with excision of any suspicious lesions prior to initiation of therapy.
  7. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
  8. Women of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to initiation of therapy.
  9. Life expectancy >12 weeks in the opinion of the Investigator.
  10. Patients must be able to understand and be willing to sign a written informed consent document.
  11. Patient must be able to swallow pills.

Exclusion Criteria:

  1. Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
  2. Syndrome of congenital QTc prolongation or QTc >500 msec.
  3. Patients with clinically significant cardiovascular disease: history of cerebrovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
  4. Pregnant or lactating women.
  5. History of hypersensitivity to vemurafenib.
  6. History of hypersensitivity to sorafenib for vemurafenib/sorafenib arm.
  7. History of hypersensitivity to crizotinib for vemurafenib/crizotinib arm.
  8. History of hypersensitivity to any component of the formulation.
  9. Patients unwilling or unable to sign informed consent document.
  10. Patients using any of the following medications: mesoridazine, dronedarone, thioridazine, ziprasidone, levomethadyl, and saquinavir for vemurafenib/sorafenib arm.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01531361

Contacts
Contact: Filip Janku, MD, PHD 713-563-1930

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Filip Janku, MD, PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01531361     History of Changes
Other Study ID Numbers: 2011-1183
Study First Received: February 6, 2012
Last Updated: December 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancies
Metastatic cancers
Vemurafenib
PLX4032
R05185426
Sorafenib
Nexavar
Bay 43-9006
Maximum tolerated dose
MTD
Dose limiting toxicity
DLT

Additional relevant MeSH terms:
Neoplasms
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014