Trial Outcomes & Findings for Akt Inhibitor MK2206 or Everolimus in Treating Patients With Refractory Kidney Cancer (NCT NCT01239342)

Last Updated: 2019-10-10

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

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

Results posted on

2019-10-10

Participant Flow

Recruitment Period: January 27, 2011 to January 9, 2013. All recruitment done in medical clinic settings.

Participant milestones

Participant milestones
Measure	MK2206 Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Overall Study STARTED	29	14
Overall Study COMPLETED	26	8
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	MK2206 Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	1	5
Overall Study Reason Unknown	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK2206 n=29 Participants Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=14 Participants Everolimus 10 mg orally once daily, courses repeat every 4 weeks.	Total n=43 Participants Total of all reporting groups
Age, Continuous	59 years n=93 Participants	63.5 years n=4 Participants	62 years n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	0 Participants n=4 Participants	8 Participants n=27 Participants
Sex: Female, Male Male	21 Participants n=93 Participants	14 Participants n=4 Participants	35 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=93 Participants	9 Participants n=4 Participants	37 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	26 Participants n=93 Participants	14 Participants n=4 Participants	40 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	29 participants n=93 Participants	14 participants n=4 Participants	43 participants n=27 Participants

PRIMARY outcome

Timeframe: 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

Population: One participant in each group left study before restaging therefore are excluded from response outcome analysis.

Outcome measures

Outcome measures
Measure	MK2206 n=28 Participants Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=13 Participants Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Median Progression Free Survival (PFS) in Months	3.68 Months Interval 1.77 to 5.75	5.98 Months Interval 5.03 to Trial met futility criteria at the planned interim analysis therefore full confidence interval was not estimable.

SECONDARY outcome

Timeframe: Up to 5 years

Population: One participant in each group left study before restaging therefore are excluded from outcome analysis.

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.

Outcome measures

Outcome measures
Measure	MK2206 n=28 Participants Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=13 Participants Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Clinical Benefit Defined as Number of Participants With Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) Complete Response	1 Participants	0 Participants
Clinical Benefit Defined as Number of Participants With Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) Partial Response	3 Participants	0 Participants
Clinical Benefit Defined as Number of Participants With Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) Stable Disease	11 Participants	11 Participants
Clinical Benefit Defined as Number of Participants With Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) Progressive Disease	13 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 5 years

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.

Outcome measures

Outcome measures
Measure	MK2206 n=29 Participants Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=14 Participants Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Hyperglycemia	7 Toxicities	1 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Hypertriglyceridemia	1 Toxicities	1 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Hyperuricemia	2 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Lymphocyte count decreased	2 Toxicities	1 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Mucositis oral	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Rash maculo-papular	8 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Pruritus	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Proteinuria	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Pancreatitis	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Lipase increased	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Generalized muscle weakness	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Dyspnea	1 Toxicities	0 Toxicities
Summary of Selected Toxicities Grade 3 or Greater Toxicity Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Dehydration	2 Toxicities	0 Toxicities

SECONDARY outcome

Timeframe: Up to 5 years

Population: One participant in each group left study before restaging therefore are excluded from response outcome analysis.

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.

Outcome measures

Outcome measures
Measure	MK2206 n=28 Participants Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=13 Participants Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Overall Response Rate (ORR) Defined as Complete Response (CR) + Partial Response (PR)	14.3 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Time interval between the date of treatment and the date of death or last follow-up, assessed up to 5 years

Overall survival reported in months as time interval between the date of treatment and the date of death or last follow-up.

Outcome measures

Outcome measures
Measure	MK2206 n=29 Participants Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=14 Participants Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
Median Overall Survival (OS) in Months	23.5 Months Interval 10.7 to 37.4	15.7 Months Interval 6.5 to "NA" as this value is not estimable due to the small sample size which generated a very wide confidence interval.

SECONDARY outcome

Timeframe: 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

Population: No participants analyzed. Data not collected.

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.

Outcome measures

Outcome data not reported

Adverse Events

MK2206

Serious events: 7 serious events

Other events: 29 other events

Deaths: 0 deaths

Everolimus

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK2206 n=29 participants at risk Akt inhibitor MK2206 200 mg orally once weekly, courses repeat every 4 weeks.	Everolimus n=14 participants at risk Everolimus 10 mg orally once daily, courses repeat every 4 weeks.
General disorders Death NOS	13.8% 4/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	7.1% 1/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Metabolism and nutrition disorders Hypercalcemia	6.9% 2/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Metabolism and nutrition disorders Dehydration	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Musculoskeletal and connective tissue disorders Musculoskeletal bone pain	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Gastrointestinal disorders Abdominal Pain	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	7.1% 1/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Infections and infestations Appendicitis	0.00% 0/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	7.1% 1/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	7.1% 1/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Gastrointestinal disorders Pancreatitis	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Vascular disorders Thromboembolic event	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.
Metabolism and nutrition disorders Hyperuricemia	3.4% 1/29 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.	0.00% 0/14 • Adverse events collected through each 28 day course, and reporting for events that occur within 30 Days of the last dose of the investigational agent.

Other adverse events

Additional Information

Eric Jonasch, MD/Professor, Genitourinary Medical Oncology

The University of Texas (UT) MD Anderson Cancer Center

Phone: 713-792-7734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60