Clinical Trial: Sorafenib Tosylate and Everolimus in Treating Patients With Advanced Solid Tumors and Metastatic Pancreatic Cancer That Does Not Respond to Gemcitabine Hydrochloride

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Study of Sorafenib and Everolimus in Patients With Advanced Solid Tumors and Gemcitabine-Refractory Metastatic Pancreatic Cancer

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: Roswell Park Cancer Institute

Current Primary Outcome:

  • 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 ]
    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 ]
    Assessed by National Cancer Institute (NCI) CTCAE v3.0.


Original Primary Outcome: To determine the 6-month overall survival of patients with previously treated gemcitabine refractory metastatic pancreatic cancer treated with the combination of sorafenib and everolimus. [ Time Frame: 6 months ]

Current Secondary Outcome:

  • Overall response rate (Phase II) [ Time Frame: Up to 1 year ]
    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 ]
  • PK parameters (Phase II) [ Time Frame: Baseline and days 1 and 15 of course 1 ]
    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 ]
  • Toxicity and adverse events as assessed by NCI CTCAE v3.0 [ Time Frame: Up to 30 days post-treatment ]
    All toxicities and adverse events in the Phase I and Phase II portions will be summarized with frequencies and descriptive measures.


Original Secondary Outcome: To determine the response rate, median survival, time to progression, CA19.9 decline and toxicity spectrum of the combination in this patient population. [ Time Frame: 6 months ]

Information By: Roswell Park Cancer Institute

Dates:
Date Received: September 21, 2009
Date Started: August 2009
Date Completion:
Last Updated: March 31, 2017
Last Verified: March 2017