Vemurafenib With Sorafenib Tosylate or Crizotinib in Treating Patients With Advanced Malignancies With BRAF Mutations
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| ClinicalTrials.gov Identifier: NCT01531361 |
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Recruitment Status :
Active, not recruiting
First Posted : February 10, 2012
Last Update Posted : May 10, 2019
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Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Malignant Neoplasm BRAF Gene Mutation Metastatic Malignant Neoplasm Recurrent Malignant Neoplasm Refractory Malignant Neoplasm | Drug: Crizotinib Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Sorafenib Tosylate Drug: Vemurafenib | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 183 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | February 6, 2012 |
| Estimated Primary Completion Date : | February 28, 2020 |
| Estimated Study Completion Date : | February 28, 2020 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (vemurafenib and sorafenib tosylate)
Patients receive vemurafenib PO BID and sorafenib tosylate PO BID on days 1-28.
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Other: Laboratory Biomarker Analysis
Correlative studies Other: Pharmacological Study Correlative studies Drug: Sorafenib Tosylate Given PO
Other Names:
Drug: Vemurafenib Given PO
Other Names:
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Experimental: Arm II (vemurafenib and crizotinib)
Patients receive vemurafenib as in Arm I and crizotinib PO QD or BID on days 1-28.
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Drug: Crizotinib
Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Pharmacological Study Correlative studies Drug: Vemurafenib Given PO
Other Names:
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Primary Outcome Measures :
- 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 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01531361
Locations
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Filip Janku | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01531361 History of Changes |
| Other Study ID Numbers: |
2011-1183 NCI-2012-00217 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2011-1183 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
| First Posted: | February 10, 2012 Key Record Dates |
| Last Update Posted: | May 10, 2019 |
| Last Verified: | May 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Additional relevant MeSH terms:
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Neoplasms, Second Primary Recurrence Neoplasms Disease Attributes Pathologic Processes Sorafenib |
Vemurafenib Crizotinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |