Clinical Trials /

Vemurafenib With Sorafenib Tosylate or Crizotinib in Treating Patients With Advanced Malignancies With BRAF Mutations

NCT01531361

Description:

This phase I clinical trial studies vemurafenib with sorafenib tosylate or crizotinib in treating patients with advanced malignancies with BRAF mutations. Sorafenib tosylate and crizotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of advanced malignancies by blocking blood flow to tumors. Drugs used in chemotherapy, such as vemurafenib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vemurafenib together with sorafenib tosylate or crizotinib may kill more cancer cells.

Related Conditions:
  • Cancer
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Vemurafenib With Sorafenib Tosylate or Crizotinib in Treating Patients With Advanced Malignancies With BRAF Mutations
  • Official Title: A Phase I Trial of Sorafenib (CRAF, BRAF, KIT, RET, VEGFR, PDGFR Inhibitor) or Crizotinib (MET, ALK, ROS1 Inhibitor) in Combination With Vemurafenib (BRAF Inhibitor) in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2011-1183
  • SECONDARY ID: NCI-2012-00217
  • SECONDARY ID: 2011-1183
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01531361

Conditions

  • Advanced Malignant Neoplasm
  • BRAF Gene Mutation
  • Metastatic Malignant Neoplasm
  • Recurrent Malignant Neoplasm
  • Refractory Malignant Neoplasm

Interventions

DrugSynonymsArms
CrizotinibMET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, XalkoriArm II (vemurafenib and crizotinib)
Sorafenib TosylateBAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenibArm I (vemurafenib and sorafenib tosylate)
VemurafenibBRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032, RG 7204, RG7204, RO 5185426, ZelborafArm I (vemurafenib and sorafenib tosylate)

Purpose

This phase I clinical trial studies vemurafenib with sorafenib tosylate or crizotinib in treating patients with advanced malignancies with BRAF mutations. Sorafenib tosylate and crizotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of advanced malignancies by blocking blood flow to tumors. Drugs used in chemotherapy, such as vemurafenib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving vemurafenib together with sorafenib tosylate or crizotinib may kill more cancer cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of
      sorafenib tosylate (sorafenib) or crizotinib in combination with vemurafenib in patients with
      advanced cancers who progressed on standard therapy.

      SECONDARY OBJECTIVES:

      I. Preliminary assessment of antitumor efficacy of sorafenib or crizotinib combination with
      vemurafenib in patients with advanced cancers.

      II. Preliminary assessment of the pharmacokinetic (PK) profile of sorafenib or crizotinib in
      combination with vemurafenib.

      III. Preliminary assessment of biomarkers.

      OUTLINE: This is a dose-escalation study of vemurafenib and sorafenib tosylate. Patients are
      assigned to 1 of 2 treatment arms by their physician.

      ARM I: Patients receive vemurafenib orally (PO) twice daily (BID) and sorafenib tosylate PO
      BID on days 1-28.

      ARM II: Patients receive vemurafenib as in Arm I and crizotinib PO once daily (QD) or BID on
      days 1-28.

      In both arms, courses repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (vemurafenib and sorafenib tosylate)ExperimentalPatients receive vemurafenib PO BID and sorafenib tosylate PO BID on days 1-28.
  • Sorafenib Tosylate
  • Vemurafenib
Arm II (vemurafenib and crizotinib)ExperimentalPatients receive vemurafenib as in Arm I and crizotinib PO QD or BID on days 1-28.
  • Crizotinib
  • Vemurafenib

Eligibility Criteria

        Inclusion Criteria:

          -  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 deoxyribonucleic acid (DNA) (tested in Clinical Laboratory Improvement
             Amendments [CLIA] lab) are also eligible

          -  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

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Absolute neutrophil count (ANC) >= 1,000/mL

          -  Platelets >= 75,000/mL

          -  Creatinine =< 2 X upper limit of normal (ULN)

          -  Total bilirubin =< 2 X ULN (exceptions may apply to benign non-malignant indirect
             hyperbilirubinemia such as Gilbert syndrome)

          -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and/or
             aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 5
             X ULN

          -  Exception for patients with liver metastasis: total bilirubin =< 3 x ULN; ALT (SGPT)
             =< 8 X ULN

          -  Dermatology evaluation with excision of any suspicious lesions prior to initiation of
             therapy

          -  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

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 2 weeks prior to initiation of therapy

          -  Life expectancy > 12 weeks in the opinion of the investigator

          -  Patients must be able to understand and be willing to sign a written informed consent
             document

          -  Patient must be able to swallow pills

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness, including, but not limited to, uncontrolled
             infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support

          -  Syndrome of congenital corrected QT interval (QTc) prolongation or QTc > 500 msec

          -  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

          -  Pregnant or lactating women

          -  History of hypersensitivity to vemurafenib

          -  History of hypersensitivity to sorafenib for vemurafenib/sorafenib arm

          -  History of hypersensitivity to crizotinib for vemurafenib/crizotinib arm

          -  History of hypersensitivity to any component of the formulation

          -  Patients unwilling or unable to sign informed consent document

          -  Patients using any of the following medications: mesoridazine, dronedarone,
             thioridazine, ziprasidone, levomethadyl, and saquinavir for vemurafenib/sorafenib arm
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of vemurafenib and sorafenib tosylate or crizotinib, defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33%
Time Frame:28 days
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

January 22, 2021