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

NCT01531361 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2011-1183NCI-2012-00217P30CA016672
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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%

  28 days

Study Arms (2)

Arm I (vemurafenib and sorafenib tosylate)

EXPERIMENTAL

Patients receive vemurafenib PO BID and sorafenib tosylate PO BID on days 1-28.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sorafenib Tosylate; Drug: Vemurafenib

Arm II (vemurafenib and crizotinib)

EXPERIMENTAL

Patients receive vemurafenib as in Arm I and crizotinib PO QD or BID on days 1-28.

Drug: Crizotinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vemurafenib

Interventions

Crizotinib DRUG

Given PO

Also known as: MET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori

Arm II (vemurafenib and crizotinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (vemurafenib and sorafenib tosylate); Arm II (vemurafenib and crizotinib)

Pharmacological Study OTHER

Correlative studies

Arm I (vemurafenib and sorafenib tosylate); Arm II (vemurafenib and crizotinib)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Arm I (vemurafenib and sorafenib tosylate)

Vemurafenib DRUG

Given PO

Also known as: BRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032, RG 7204, RG7204, RO 5185426, Zelboraf

Arm I (vemurafenib and sorafenib tosylate); Arm II (vemurafenib and crizotinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence; Neoplasms

Interventions

Crizotinib; Sorafenib; Vemurafenib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Sulfonamides; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Filip Janku

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2012
• First Posted: February 10, 2012
• Study Start: February 6, 2012
• Primary Completion: January 13, 2021
• Study Completion: January 13, 2021
• Last Updated: January 22, 2021

Record last verified: 2021-01

Locations

US (1)