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Akt Inhibitor MK2206 or Everolimus in Treating Patients With Refractory Kidney Cancer | Clinical Trials | Clareo Health

TERMINATEDPHASE2

Akt Inhibitor MK2206 or Everolimus in Treating Patients With Refractory Kidney Cancer

A Randomized Phase 2 Study of MK-2206 in Comparison With Everolimus in Refractory Renal Cell Carcinoma

NCT01239342•National Cancer Institute (NCI)

Summary

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.

Detailed Description

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histologically or cytologically confirmed metastatic or unresectable RCC; all histologies are permitted; patient should have undergone nephrectomy
•Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
•Patients must have received, and progressed on an anti-VEGF therapy, including bevacizumab, sorafenib, sunitinib or pazopanib
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
•Leukocytes \>= 3,000/mcL
•Absolute neutrophil count \>= 1,500/mcL
•Platelets \>= 100,000/mcL
•Total bilirubin within normal institutional limits
•Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
•Serum creatinine =\< 1.5 x upper limit of normal (ULN)
+4 more criteria

Exclusion Criteria

•Patients who received oral tyrosine-kinase inhibitors (TKIs) (sorafenib, sunitinib, or pazopanib) within 2 weeks prior to entering the study, radiotherapy, immunotherapy or chemotherapy within 4 weeks prior to entering the study, bevacizumab within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (recovered to =\< grade 1)
•Patients may not be receiving any other investigational agents; patients may not have received an mammalian target of rapamycin (mTOR) inhibitor
•Patients with known brain metastases should be excluded from this clinical trial
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study
•Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP4503A4) are ineligible
•Patient should have a hemoglobin A1C value of \< 8%; preclinical studies demonstrated the potential of MK-2206 for induction of hyperglycemia in all preclinical species tested; studies also demonstrate a risk of hyperglycemia, hyperlipidemia and hypertriglyceridemia associated with everolimus therapy; patients with diabetes or in risk for hyperglycemia, hyperlipidemia and/or hypertriglyceridemia should not be excluded from trials with MK-2206 or everolimus, but the patient should be well controlled on oral agents (recent \[i.e. within 3 months\] hemoglobin \[Hb\]A1C =\< 7.0) before the patient enters the trial
•Baseline corrected Fridericia QT interval (QTcF) \> 450 msec (male) or QTcF \> 470 msec (female) will exclude patients from entry on study
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
•Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-2206 or everolimus
•Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
+1 more criteria

Locations (8)

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

Key Dates

Start Date

January 27, 2011

Primary Completion Date

September 19, 2018

Completion Date

September 19, 2018

Last Updated

October 10, 2019

Enrollment

ACTUAL participants

Conditions

Metastatic Kidney CarcinomaRecurrent Renal Cell CarcinomaStage III Renal Cell Cancer AJCC v7Stage IV Renal Cell Cancer AJCC v7

Interventions

Akt Inhibitor MK2206

DRUG

Everolimus

DRUG

Laboratory Biomarker Analysis

OTHER

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 10, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Akt Inhibitor MK2206 or Everolimus in Treating Patients With Refractory Kidney Cancer

Inclusion Criteria

Exclusion Criteria

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