Cabozantinib-S-Malate and Vemurafenib in Treating Patients With Solid Tumors or Melanoma That is Metastatic or That Cannot Be Removed By Surgery
|ClinicalTrials.gov Identifier: NCT01835184|
Recruitment Status : Terminated
First Posted : April 18, 2013
Last Update Posted : September 25, 2014
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Melanoma Stage IIIA Melanoma Stage IIIB Melanoma Stage IIIC Melanoma Stage IV Melanoma Unspecified Adult Solid Tumor, Protocol Specific||Drug: cabozantinib-s-malate Drug: vemurafenib Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
I. To determine a tolerable dose of XL184 (cabozantinib-s-malate) in combination with vemurafenib.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Escalation of the MET Inhibitor XL184 and the BRAF Inhibitor Vemurafenib|
|Study Start Date :||May 2013|
|Actual Primary Completion Date :||September 2014|
Experimental: Treatment (cabozantinib-s-malate, vemurafenib)
Patients receive cabozantinib-s-malate PO QD and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Other: pharmacological study
Other Name: pharmacological studies
- Maximum tolerable dose of cabozantinib-s-malate in combination with vemurafenib based on the incidence of dose-limiting toxicity (DLT) graded according to the National Cancer Institute CTCAE version 4.0. [ Time Frame: 28 days ]DLT is defined as the occurrence of grade 4 hematologic toxicity, grade 3 or 4 non-hematologic toxicity including diarrhea, or nausea and vomiting.
- ORR (complete response [CR]+partial response [PR]) assessed using RECIST criteria [ Time Frame: Up to 4 weeks after last dose of therapy ]Calculated and presented with 90% exact binomial confidence intervals.
- DCR per RECIST version 1.1 [ Time Frame: Up to 4 weeks after last dose of therapy ]Rate will be calculated and presented with 90% exact binomial confidence intervals.
- PFS per RECIST version 1.1 [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after last dose of therapy ]Summarized using the method of Kaplan-Meier. Median PFS will be presented with 90% confidence intervals derived using log (-log [survival]) methodology.
- Change in met proto-oncogene (MET) expression by immunohistochemistry (IHC) [ Time Frame: Baseline and after 4 weeks of therapy ]Expression will be classified as positive or negative at each time based upon established methodology. The proportions of patients with concordant/discordant biomarker assessments will be presented with 90% exact binomial confidence intervals.
- Change in serum levels of hepatocyte growth factor (HGF) by IHC [ Time Frame: Baseline to up to 8 weeks ]Assay levels of HGF in the serum will be summarized graphically. The status of the assay (+/-) will be shown at each assessment time for each patient while on study therapy. Graphics will note changes in disease status and times of disease progression.
- Clinical benefit (CR, PR, or stable disease), assessed according to RECIST [ Time Frame: Up to 4 weeks after last dose of therapy ]To investigate the relationship between pre-treatment expressions of MET, phospho-MET, or HGF and measures of response or clinical benefit, pre-treatment ratios of total MET to phospho-MET will be calculated and summarized by response or clinical benefit status using descriptive statistics.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01835184
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Jason Luke||Dana-Farber Cancer Institute|