Sorafenib Tosylate and Everolimus in Treating Patients With Advanced Solid Tumors and Metastatic Pancreatic Cancer That Does Not Respond to Gemcitabine Hydrochloride
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Sorafenib and Everolimus in Patients With Advanced Solid Tumors and Gemcitabine-Refractory Metastatic Pancreatic Cancer|
- Overall survival (Phase II) [ Time Frame: Time from date of subject enrollment to the date of death due to any cause, assessed up to 6 months ] [ Designated as safety issue: No ]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.
- Maximum tolerated dose of everolimus (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]Assessed by National Cancer Institute (NCI) CTCAE v3.0.
- Overall response rate (Phase II) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Will be computed with a corresponding exact 95% confidence interval.
- Differences in biomarkers between responders and non-responders (Phase II) [ Time Frame: Baseline and days 1 and 15 of course 1 ] [ Designated as safety issue: No ]
- PK parameters (Phase II) [ Time Frame: Baseline and days 1 and 15 of course 1 ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]
- Toxicity and adverse events as assessed by NCI CTCAE v3.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]All toxicities and adverse events in the Phase I and Phase II portions will be summarized with frequencies and descriptive measures.
|Study Start Date:||August 2009|
|Study Completion Date:||December 2012|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (sorafenib tosylate and everolimus)
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.
Drug: sorafenib tosylate
Other Names:Drug: everolimus
Other Names:Other: laboratory biomarker analysis
Correlative studyOther: pharmacogenomic studies
Other Name: Pharmacogenomic StudyOther: pharmacological study
Other Name: pharmacological studies
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00981162
|United States, Colorado|
|University of Colorado at Denver Health Sciences Center|
|Aurora, Colorado, United States, 80045|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Wen Wee Ma||Roswell Park Cancer Institute|