This randomized phase I trial is studying the side effects and best dose of everolimus, gemcitabine hydrochloride, and cisplatin in treating patients with unresectable solid tumors refractory to standard therapy. Drugs used in chemotherapy, such as everolimus, gemcitabine hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of concurrently administered everolimus and gemcitabine (gemcitabine hydrochloride) in patients with advanced, refractory solid tumors (two-agent MTD). II. To determine the maximally tolerated dose of concurrently administered everolimus, gemcitabine and cisplatin in patients with advanced, refractory solid tumors (three-agent MTD). III. To describe the toxicity of the two treatment combinations. IV. To describe any evidence of the antitumor activity of the two treatment combinations. V. To obtain pilot data on toxicity and efficacy outcome of everolimus, gemcitabine and cisplatin in patients with cholangiocarcinoma or gallbladder carcinoma. (Cohort III) OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride and everolimus. COHORT I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and everolimus orally (PO) once daily or 3 times weekly. COHORT II: Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 1 hour on days 1 and 8 and everolimus PO once daily or 3 times weekly. COHORT III: Patients receive treatment as in cohort II. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic
Rochester, Minnesota, United States
Adverse events profile
Tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Time frame: Up to 3 months post-treatment
Toxicity profile per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Toxicity Criteria (CTC) standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Time frame: Up to 3 months post-treatment
MTD of the combination of everolimus, gemcitabine hydrochloride, and cisplatin
Toxicity assessed by NCI CTCAE v3.0.
Time frame: 3 weeks
Response profile
Best response is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria will be used for tumor evaluation. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).
Time frame: Up to 5 years
Timed endpoints
The data on time-related variables will be summarized descriptively. These include time until any treatment related toxicity, time until treatment related grade 3+ toxicity, time until hematologic nadirs (white blood cells \[WBC\], ANC, platelets), time to progression and time to treatment failure, where time to treatment failure is defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.
Time frame: Up to 5 years
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