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Vemurafenib With Sorafenib Tosylate or Crizotinib in Treating Patients With Advanced Malignancies With BRAF Mutations | Clinical Trials | Clareo Health

COMPLETEDPHASE1

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

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

NCT01531361•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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
+5 more criteria

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

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

February 6, 2012

Primary Completion Date

January 13, 2021

Completion Date

January 13, 2021

Last Updated

January 22, 2021

Enrollment

ACTUAL participants

Conditions

Advanced Malignant NeoplasmBRAF Gene MutationMetastatic Malignant NeoplasmRecurrent Malignant NeoplasmRefractory Malignant Neoplasm

Interventions

Crizotinib

DRUG

Laboratory Biomarker Analysis

OTHER

Pharmacological Study

OTHER

Sorafenib Tosylate

DRUG

Vemurafenib

DRUG

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

NCT04585750

Advanced Solid TumorAdvanced Malignant Neoplasm+28 more

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RECRUITING

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 22, 2021Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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