Trial Outcomes & Findings for Selumetinib and Akt Inhibitor MK2206 in Treating Patients With Stage III or Stage IV Melanoma Who Failed Prior Therapy With Vemurafenib or Dabrafenib (NCT NCT01519427)

NCT ID: NCT01519427

Last Updated: 2014-06-18

Results Overview

Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) \>=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

On-treatment date to date of progressive disease (assessed up to 30 days after end of treatment)

Results posted on

2014-06-18

Participant Flow

Subjects were recruited from January 2012 through February 2013.

Four potential subjects consented. Two were ineligible.

Participant milestones

Participant milestones
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Overall Study
STARTED
2
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Overall Study
disease progression
2

Baseline Characteristics

Selumetinib and Akt Inhibitor MK2206 in Treating Patients With Stage III or Stage IV Melanoma Who Failed Prior Therapy With Vemurafenib or Dabrafenib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
n=2 Participants
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Age, Categorical
<=18 years
0 Participants
n=39 Participants
Age, Categorical
Between 18 and 65 years
2 Participants
n=39 Participants
Age, Categorical
>=65 years
0 Participants
n=39 Participants
Age, Continuous
44 years
STANDARD_DEVIATION 14 • n=39 Participants
Sex: Female, Male
Female
1 Participants
n=39 Participants
Sex: Female, Male
Male
1 Participants
n=39 Participants
Region of Enrollment
United States
2 participants
n=39 Participants

PRIMARY outcome

Timeframe: On-treatment date to date of progressive disease (assessed up to 30 days after end of treatment)

Population: All patients with best overall response data; patients are excluded if best overall response data is missing or if the patient is non-evaluable for best overall response.

Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) \>=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), \>=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR\>PR\>SD\>PD.

Outcome measures

Outcome measures
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
n=2 Participants
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Objective Response
Complete response
0 participants
Objective Response
Partial response
0 participants
Objective Response
Progressive disease
1 participants
Objective Response
Stable disease
1 participants

SECONDARY outcome

Timeframe: Before initiation of treatment and at 7-14 days, up to 2 years

Population: This clinical trial was terminated early. The investigators did not perform any biomarker expression analyses.

Pre-treatment tumor biopsy tissue and blood and day 7-14 tumor biopsy tissue and blood will be examined by immunohistochemistry for expression and phosphorylation of the proteins pERK, pMEK, pAKT, Ki67, pRpS6, CRAF, cyclin D, PDGFr, pPDGFr. IGFr1, and COT/Tp12 for changes from baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: On-study to lesser of date of progression or date of death from any cause, up to 2 years

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where either death or progression is an event, with censoring for non-progressed, non-expired patients at greater of off-study date or last known date alive.

Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: \>= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions

Outcome measures

Outcome measures
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
n=2 Participants
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Progression-free Survival (PFS)
105 days
Interval 42.0 to 168.0

SECONDARY outcome

Timeframe: On-study date to date of death from any cause, up to 2 years

Population: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.

Estimated probable duration of life from on-study date to date of death from any cause, using Kaplan-Meier method with censoring (see Analysis Population Description for additional details).

Outcome measures

Outcome measures
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
n=2 Participants
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Overall Survival
153 days
Interval 117.0 to 189.0

Adverse Events

Treatment (Selumetinib and Akt Inhibitor MK2206)

Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
n=2 participants at risk
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Renal and urinary disorders
Urinary tract obstruction
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Blood and lymphatic system disorders
anemia
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Musculoskeletal and connective tissue disorders
pelvic pain
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Renal and urinary disorders
acute renal failure
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)

Other adverse events

Other adverse events
Measure
Treatment (Selumetinib and Akt Inhibitor MK2206)
n=2 participants at risk
Patients receive selumetinib PO BID on days 1-21 and Akt inhibitor MK2206 PO once weekly.
Nervous system disorders
Nervous system disorders - Other
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Blood and lymphatic system disorders
lymphocyte count decreased
50.0%
1/2 • Number of events 2 • day 0 through day 168 (week 24)
Blood and lymphatic system disorders
anemia
50.0%
1/2 • Number of events 5 • day 0 through day 168 (week 24)
Cardiac disorders
electrocardiogram QT corrected interval prolonged
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Gastrointestinal disorders
vomiting
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Infections and infestations
bladder infection
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Infections and infestations
urinary tract infection
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Investigations
alanine aminotransferase increased
100.0%
2/2 • Number of events 6 • day 0 through day 168 (week 24)
Investigations
aspartate aminotransferase increased
50.0%
1/2 • Number of events 2 • day 0 through day 168 (week 24)
Investigations
creatinine increased
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Metabolism and nutrition disorders
anorexia
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Metabolism and nutrition disorders
hyperglycemia
100.0%
2/2 • Number of events 5 • day 0 through day 168 (week 24)
Metabolism and nutrition disorders
hypoalbuminemia
50.0%
1/2 • Number of events 3 • day 0 through day 168 (week 24)
Metabolism and nutrition disorders
hypokalemia
50.0%
1/2 • Number of events 2 • day 0 through day 168 (week 24)
Metabolism and nutrition disorders
hyponatremia
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Musculoskeletal and connective tissue disorders
pain in extremity
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
tumor pain
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
General disorders
pain
100.0%
2/2 • Number of events 2 • day 0 through day 168 (week 24)
Eye disorders
blurred vision
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Eye disorders
pain eye
50.0%
1/2 • Number of events 2 • day 0 through day 168 (week 24)
Renal and urinary disorders
hematuria
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Skin and subcutaneous tissue disorders
rash maculo-papular
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Vascular disorders
lymphedema
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
General disorders
chills
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
General disorders
fatigue
50.0%
1/2 • Number of events 2 • day 0 through day 168 (week 24)
Musculoskeletal and connective tissue disorders
pain extremity
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Musculoskeletal and connective tissue disorders
Arthralgia
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Cardiac disorders
Atrial fibrillation
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Psychiatric disorders
Depression
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)
Gastrointestinal disorders
Diarrhea
50.0%
1/2 • Number of events 1 • day 0 through day 168 (week 24)

Additional Information

Jeff Sosman, MD

Vanderbilt-Ingram Cancer Center

Phone: 615-936-3048

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60