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

NCT01239342 | Terminated Phase 2 Results

• 10 other identifiers: NCI-2010-02270NCI 8727MDA-2010-0247CDR00006884572010-02478727N01CM00038N01CM00039N01CM62202P30CA016672
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Metastatic Kidney Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• 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 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

Secondary Outcomes (5)

• Clinical Benefit Defined as Number of Participants With Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)

  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

  Up to 5 years

• Overall Response Rate (ORR) Defined as Complete Response (CR) + Partial Response (PR)

  Up to 5 years

• Median Overall Survival (OS) in Months

  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)

  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

Study Arms (2)

Arm I (Akt inhibitor MK2206)

EXPERIMENTAL

Patients receive Akt inhibitor MK2206 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.

Drug: Akt Inhibitor MK2206; Other: Laboratory Biomarker Analysis

Arm II (everolimus)

EXPERIMENTAL

Patients receive everolimus PO QD on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Everolimus; Other: Laboratory Biomarker Analysis

Interventions

Akt Inhibitor MK2206 DRUG

Given PO

Also known as: MK2206

Arm I (Akt inhibitor MK2206)

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Arm II (everolimus)

Laboratory Biomarker Analysis OTHER

Optional correlative studies

Arm I (Akt inhibitor MK2206); Arm II (everolimus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• International normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x ULN; therapeutic anticoagulation with warfarin is allowed if target INR =\< 3 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for \> 2 weeks at time of randomization
• Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 8 weeks after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Serum pregnancy test in female patients of childbearing potential must be negative within 24 hours of enrolling on this study

You may not qualify if:

• 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
• Individuals who are diagnosed with an intercurrent cancer are excluded, with the exception of non-melanoma skin cancers, and other cancers where curative treatment was completed at least two years ago

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

Tower Cancer Research Foundation

Beverly Hills, California, 90211, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

MK 2206; Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Eric Jonasch, MD/Professor, Genitourinary Medical Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

EJonasch@mdanderson.org

713-792-7734

Study Officials

• Eric Jonasch

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 11, 2010
• Study Start: January 27, 2011
• Primary Completion: September 19, 2018
• Study Completion: September 19, 2018
• Last Updated: October 10, 2019
• Results First Posted: June 7, 2017

Record last verified: 2019-09

Locations

US (8)