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Cabozantinib-S-Malate and Vemurafenib in Treating Patients With Solid Tumors or Melanoma That is Metastatic or That Cannot Be Removed By Surgery | Clinical Trials | Clareo Health

TERMINATEDPHASE1

Cabozantinib-S-Malate and Vemurafenib in Treating Patients With Solid Tumors or Melanoma That is Metastatic or That Cannot Be Removed By Surgery

Phase I Dose Escalation of the MET Inhibitor XL184 and the BRAF Inhibitor Vemurafenib

NCT01835184•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase I trial studies the side effects and best dose of cabozantinib-s-malate when given together with vemurafenib in treating patients with solid tumors or melanoma that is metastatic or that cannot be removed by surgery. Cabozantinib-s-malate and vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES: I. To determine a tolerable dose of XL184 (cabozantinib-s-malate) in combination with vemurafenib. SECONDARY OBJECTIVES: I. To determine the objective response rate (ORR) and disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. II. To determine the progression-free survival (PFS). III. To determine the response rate according to the molecular phenotype. OUTLINE: This is a dose-escalation study of cabozantinib-s-malate. Patients receive cabozantinib-s-malate orally (PO) once daily (QD) and vemurafenib PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients entered on the dose-escalation portion of the trial must have a histologically confirmed solid tumor malignancy that is metastatic or unresectable and molecularly confirmed to harbor a mutation in v-raf murine sarcoma viral oncogene homolog (BRAF) at V600
•Patients entered on the dose expansion portion of the study must have histologically and molecularly confirmed malignant melanoma that is metastatic or unresectable and found to be harbor a mutation in BRAF at V600
•Patients in the dose escalation portion of the study may have had none or any number of prior therapies
•Patients in the dose expansion portion may have any number of prior therapies but must have been treated with a selective BRAF inhibitor (including but not necessarily limited to vemurafenib, trametinib, Raf kinase inhibitor LGX818 \[LGX818\]) as their prior line of therapy, and had documented stable disease for at least 4 months or disease progression, as interpreted by the accruing investigator; there is no minimum period of treatment with a BRAF inhibitor required prior to determination of progression; documentation of progression on a selective BRAF inhibitor may not have taken place more than 1 month prior to enrollment on this study
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
•Leukocytes \>= 3,000/mcL
•Absolute neutrophil count \>= 1,000/mcL
•Platelets \>= 100,000/mcL
•Total bilirubin =\< 1.5 × upper limit of normal (ULN)
•Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 × institutional upper limit of normal
+12 more criteria

Exclusion Criteria

•Prior treatment with XL184 (cabozantinib) or other mesenchymal-epithelial transition (MET) directed therapy
•The subject has received radiation therapy:
•* To the thoracic cavity, abdomen, or pelvis within 3 months before the first dose of study treatment, or has ongoing complications, or is without complete recovery and healing from prior radiation therapy
•* To bone metastasis within 14 days before the first dose of study treatment
•The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment
•The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia, rash, and other non-clinically significant adverse events (AEs)
•The subject has unstable brain metastases or epidural disease; subjects with brain metastases who are treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic following treatment and do not require steroid treatment for 2 weeks before starting study treatment are eligible (BRAF inhibitor should be continued through this period if possible); neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans for subjects with known brain metastases is required to confirm eligibility; the use of anti-convulsant medications are allowed only if these are non-enzyme inducing anti-epileptic agents (NEIAED) including but not limited to valproate, benzodiazepines, gabapentin, lamotrigine, levetiracetam, tiagabine and zonisamide
•The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \>= 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
•The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor xabans (Xa) inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=\< 81 mg/day), low-dose warfarin (=\< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
•The subject requires chronic concomitant treatment of strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort); as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; concomitant medications that are primarily metabolized by the cytochrome P450 (CYP450) ) family 1, subfamily A, polypeptide 2 (1A2), 3A4 and family 2, subfamily C, polypeptide 9 (2C9) as well as those that strongly inhibit or induce CYP3A4 should be used with caution with vemurafenib; the categories of drugs listed below if used, should be monitored with caution for potential alterations in drug exposure and toxicity
+53 more criteria

Locations (3)

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Key Dates

Start Date

May 1, 2013

Primary Completion Date

September 1, 2014

Last Updated

September 25, 2014

Enrollment

ACTUAL participants

Conditions

Recurrent MelanomaStage IIIA MelanomaStage IIIB MelanomaStage IIIC MelanomaStage IV MelanomaUnspecified Adult Solid Tumor, Protocol Specific

Interventions

cabozantinib-s-malate

DRUG

vemurafenib

DRUG

laboratory biomarker analysis

OTHER

pharmacological study

OTHER

Dinaciclib in Treating Patients With Stage IV Melanoma

NCT00937937

Acral Lentiginous MelanomaCutaneous Nodular Melanoma+5 more

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ACTIVE_NOT_RECRUITINGPHASE1

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

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Advanced Malignant Solid NeoplasmRecurrent Melanoma+6 more

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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: September 25, 2014Data 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

Cabozantinib-S-Malate and Vemurafenib in Treating Patients With Solid Tumors or Melanoma That is Metastatic or That Cannot Be Removed By Surgery

Inclusion Criteria

Exclusion Criteria

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