This randomized phase II trial studies the side effects and how well Akt inhibitor MK2206 or everolimus works in treating patients with kidney cancer that does not respond to treatment. Akt inhibitor MK2206 and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether Akt inhibitor MK2206 or everolimus is more effective in treating kidney cancer.
PRIMARY OBJECTIVES: I. To assess progression free survival (PFS) of vascular endothelial growth factor (VEGF) therapy refractory renal cell carcinoma (RCC) patients who receive either MK-2206 (Akt inhibitor MK-2206) or everolimus. II. To assess safety of MK-2206 in patients with VEGF therapy refractory RCC. SECONDARY OBJECTIVES: I. To assess overall response rate (ORR) and overall survival (OS). (Clinical) II. To assess time to treatment failure (TTF). (Clinical) III. To determine whether baseline AKT activation is predictive for clinical benefit after treatment with MK-2206 or everolimus. (Pre-clinical/exploratory) IV. To determine whether circulating cytokines and angiogenic factors predict for clinical benefit after treatment with MK-2206 or everolimus. (Pre-clinical/exploratory) V. To assess impact of karyotype on outcome in patients treated with MK-2206 or everolimus. (Pre-clinical/exploratory) OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who are progression free after 1 year may receive a 12 week study drug supply of Akt inhibitor MK2206. ARM II: Patients receive everolimus PO once daily (QD) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Tower Cancer Research Foundation
Beverly Hills, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
M D Anderson Cancer Center
Houston, Texas, United States
Median Progression Free Survival (PFS) in Months
PFS defined as Time interval between date of treatment and date of disease progression, date of death or last follow-up date, whichever occurs first. Progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions.
Time frame: Time interval between date of treatment and date of disease progression, date of death or last follow-up date, whichever occurs first, assessed up to 5 years
Clinical Benefit Defined as Number of Participants With Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)
Clinical benefit defined as participants' with CR+PR+SD assessed using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Repeat radiologic studies to evaluate disease progression or response (in accordance with restaging of disease) every 8 weeks. Complete Response (CR): Disappearance all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): \>30% decrease in sum diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): \>20% increase in sum diameters of target lesions, reference smallest sum on study (includes baseline sum if is smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase \>5 mm. (Note: appearance 1/+ new lesions considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters.
Time frame: Up to 5 years
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Adverse Events (AEs) list of reported events with associated intervention agent in a uniform presentation of events. The method of Thall, Simon and Estey (1995, 1996) was used to collect study participants' safety data summarized by treatment arm, category, severity and relevance. Comprehensive listing of AEs collected on study can be found in Adverse Event section separated by severity, Serious and Other AEs and represented by treatment arm, organ system-category within defined severity.
Time frame: Up to 5 years
Overall Response Rate (ORR) Defined as Complete Response (CR) + Partial Response (PR)
Response for CR + PR defined by RECIST version 1.1. Repeat radiologic studies to evaluate disease progression or response (in accordance with restaging of disease) every 8 weeks. Complete Response (CR): Disappearance all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): \>30% decrease in sum diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): \>20% increase in sum diameters of target lesions, reference smallest sum on study (includes baseline sum if is smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase \>5 mm. (Note: appearance 1/+ new lesions considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters.
Time frame: Up to 5 years
Median Overall Survival (OS) in Months
Overall survival reported in months as time interval between the date of treatment and the date of death or last follow-up.
Time frame: Time interval between the date of treatment and the date of death or last follow-up, assessed up to 5 years
Time to Failure (TTF)
TTF defined as Time interval between the date of treatment and the date of disease progression, date of death, date of treatment discontinuation due to severe toxicity or last follow-up date.
Time frame: Time interval between the date of treatment and the date of disease progression, date of death, date of treatment discontinuation due to severe toxicity or last follow-up date, assessed up to 5 years
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