This phase I/II trial is studying the side effects and best dose of everolimus when given together with sorafenib tosylate and to see how well they work in treating patients with advanced solid tumors and metastatic pancreatic cancer that does not respond to gemcitabine hydrochloride. Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Giving sorafenib tosylate together with everolimus may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the 6-month overall survival of patients with previously treated gemcitabine (gemcitabine hydrochloride)-refractory metastatic pancreatic cancer treated with the combination of sorafenib (sorafenib tosylate) and everolimus. II. To determine the recommended Phase II dose of everolimus when administered in combination with sorafenib in patients with advanced solid tumors. SECONDARY OBJECTIVES: I. To determine the response rate, median survival, time to progression, CA 19.9 decline and toxicity spectrum of the combination in this patient population. II. To characterize the pharmacokinetic (PK) profiles of sorafenib and everolimus when given in combination. III. To explore the biomarkers that correlate with response to the study combination in patients previously treated with gemcitabine-refractory metastatic pancreas cancer. OUTLINE: This is a phase I, dose-escalation study of everolimus, followed by a phase II study. Patients receive everolimus (PO) once daily and sorafenib tosylate PO twice daily 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 every 3 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
University of Colorado at Denver Health Sciences Center
Aurora, Colorado, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Overall survival (Phase II)
The estimated distribution of overall survival will be obtained using the product-limit based Kaplan-Meier method. Estimates of quantities such as median survival will be obtained.
Time frame: Time from date of subject enrollment to the date of death due to any cause, assessed up to 6 months
Maximum tolerated dose of everolimus (Phase I)
Assessed by National Cancer Institute (NCI) CTCAE v3.0.
Time frame: 28 days
Overall response rate (Phase II)
Will be computed with a corresponding exact 95% confidence interval.
Time frame: Up to 1 year
Differences in biomarkers between responders and non-responders (Phase II)
Time frame: Baseline and days 1 and 15 of course 1
PK parameters (Phase II)
Will be summarized in each cohort of patients. Comparison of PK parameters among the dose levels will be performed using non-parametric statistical methods for K-independent samples.
Time frame: Baseline and days 1 and 15 of course 1
Correlation of predicted drug concentration or area under the curve (AUC) with biomarker response for each drug and/or in combination (Phase II)
Time frame: Baseline and days 1 and 15 of course 1
Toxicity and adverse events as assessed by NCI CTCAE v3.0
All toxicities and adverse events in the Phase I and Phase II portions will be summarized with frequencies and descriptive measures.
Time frame: Up to 30 days post-treatment
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