RATIONALE: Panobinostat and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving panobinostat together with everolimus and to see how well they work in treating patients with metastatic or unresectable renal cell cancer that does not respond to treatment with sunitinib malate or sorafenib tosylate
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability and determine the recommended dosing for the combination of LBH589 and Everolimus in patients with metastatic renal cell carcinoma. (Phase I) II. To assess the preliminary evidence of tumor response in patients treated with LBH589 and Everolimus. (Phase I) III. To evaluate the effect of LBH589 and Everolimus on the progression-free survival event rate. (Phase II) IV. To determine the clinical response rate of LBH589 and Everolimus in patients with metastatic renal cell carcinoma. (Phase II) SECONDARY OBJECTIVES: I. To determine the toxicity of the combination of LBH589 and Everolimus in patients with metastatic renal cell carcinoma. (Phase II) II. To evaluate the effect of LBH589 and Everolimus on time-to-tumor-progression (TTP), disease-free survival and overall survival. (Phase II) III. To assess the pharmacodynamic effects of LBH589 and Everolimus in peripheral blood mononuclear cells (PBMNC) and tumor that are accessible before and after treatment, if available. (Phase II) IV. To evaluate the modulation of tumor metabolism and blood in patients treated with LBH589 and Everolimus by FDG and 015 water PET/CT scan. (Phase II) OUTLINE: This is a dose-escalation study of panobinostat and everolimus, followed by a phase II study. Patients receive oral panobinostat once daily on days 1, 3, 4, 8, 10, and 12 and oral everolimus once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for at least 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Given orally
Given orally
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Roswell Park Cancer Institute
Buffalo, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Progression-free Survival (PFS)
6 month PFS survival rate. Calculated as the total number of failures (deaths or progression) divided by the total follow-up or exposure time of patients on study. Assessed using Kaplan Meier and Proportional Hazards.
Time frame: The time from registration to documentation of disease progression up to 3 years
Number of Participants With Clinical Response
Number of participants with clinical response. Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors ver 1.0 Committee \[JNCI 92(3):205-216, 2000\]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST ver. 1.0 criteria.
Time frame: The time from registration up to 3 years
Number of Participants With an Adverse Event.
Number of participants with an adverse event. Please refer to the adverse event reporting for more detail.
Time frame: The time from registration up to 3 years
Median Progression Free Survival
Median progression free survival. Assessed using Kaplan Meier and Proportional Hazards.
Time frame: The time from registration up to 3 years
6-month Overall Survival Rate
6-month overall survival rate
Time frame: The time from registration up to 3 years
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