Trial Outcomes & Findings for Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery (NCT NCT01802320)

Last Updated: 2019-09-20

Results Overview

Complete Response (CR): Disappearance all target lesions. Any pathological lymph nodes 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 smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of \>5 mm. (Note: appearance of 1/\> new lesions also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Up to 18 months

Results posted on

2019-09-20

Participant Flow

Recruitment Period: March 07, 2013 to July 14, 2015. All recruitment done at The University of Texas MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	Treatment (Akt Inhibitor MK2206) Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	18
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Akt Inhibitor MK2206) Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Overall Study Death	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Akt Inhibitor MK2206) n=18 Participants Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Age, Continuous	56 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 18 months

Outcome measures

Outcome measures
Measure	Treatment (Akt Inhibitor MK2206) n=18 Participants Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Overall Response Rate (CR+PR) Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	0 Participants

SECONDARY outcome

Timeframe: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 18 months

Population: Outcome data not collected, no analysis to be performed as participants had related tumor response.

Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for DR.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 18 months

Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for OS.

Outcome measures

Outcome measures
Measure	Treatment (Akt Inhibitor MK2206) n=18 Participants Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS)	6.8 months Interval 5.83 to 7.77

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 18 months

Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for PFS.

Outcome measures

Outcome measures
Measure	Treatment (Akt Inhibitor MK2206) n=18 Participants Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS)	1.87 months Interval 1.83 to 1.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 18 months

Population: Given the lack of response seen in this study, biomarker validation and correlation of biomarker enrichment with clinical outcome is not feasible. Data were not collected.

Samples will be analyzed using the Wilcoxon rank test. Chi-square or Fisher's exact test where appropriate will be used to determine whether high levels of marker expression correlate with PTEN status.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Akt Inhibitor MK2206)

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Akt Inhibitor MK2206) n=18 participants at risk Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Small Bowel Obstruction	11.1% 2/18 • Number of events 3 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Abdominal pain	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Cardiac disorders Cardiac Arrest	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Injury, poisoning and procedural complications Fracture, Arm	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months

Other adverse events

Other adverse events
Measure	Treatment (Akt Inhibitor MK2206) n=18 participants at risk Akt inhibitor MK2206 orally on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Abdominal pain	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Injury, poisoning and procedural complications Acute kidney injury	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Psychiatric disorders Agitation	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Alanine aminotransferase increased	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Alkaline phosphatase increased	38.9% 7/18 • Number of events 9 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Anal pain	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Blood and lymphatic system disorders Anemia	33.3% 6/18 • Number of events 10 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Anorexia	22.2% 4/18 • Number of events 6 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Aspartate aminotransferase increased	27.8% 5/18 • Number of events 5 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Musculoskeletal and connective tissue disorders Back pain	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Bloating	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Blood bilirubin increased	27.8% 5/18 • Number of events 7 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Eye disorders Blurred vision	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Eye disorders Conjunctivitis	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Constipation	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Cough	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Creatinine increased	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Dehydration	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Diarrhea	55.6% 10/18 • Number of events 12 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Dry skin	16.7% 3/18 • Number of events 4 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Nervous system disorders Dysarthria	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Nervous system disorders Dysgeusia	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Dyspepsia	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 3/18 • Number of events 3 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Eye disorders Eye disorders - (Other	5.6% 1/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
General disorders Fatigue	38.9% 7/18 • Number of events 9 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
General disorders Fever	16.7% 3/18 • Number of events 3 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Musculoskeletal and connective tissue disorders Flank pain	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Eye disorders Floaters	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
General disorders Flu like symptoms	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Injury, poisoning and procedural complications Fracture	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Musculoskeletal and connective tissue disorders Gait disturbance	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Nervous system disorders Headache	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Hemorrhoids	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Hiccups	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypercalcemia	11.1% 2/18 • Number of events 4 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hyperglycemia	61.1% 11/18 • Number of events 17 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hyperkalemia	22.2% 4/18 • Number of events 4 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Vascular disorders Hypertension	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypertriglyceridemia	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypocalcemia	11.1% 2/18 • Number of events 3 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypokalemia	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypomagnesemia	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hyponatremia	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Hypophosphatemia	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Psychiatric disorders Insomnia	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Lactate dehydrogenase (LDH) elevated	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Metabolism and nutrition disorders Metabolism and nutrition disorders - (Other)	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Mucosal infection	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Mucositis oral	16.7% 3/18 • Number of events 3 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Nail discoloration	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Nail ridging	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Nausea	55.6% 10/18 • Number of events 14 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Musculoskeletal and connective tissue disorders Neck pain	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive Disease	44.4% 8/18 • Number of events 8 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Neutrophil count decreased	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
General disorders Pain	27.8% 5/18 • Number of events 5 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Pain of skin	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Nervous system disorders Peripheral sensory neuropathy	11.1% 2/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Infections and infestations Pharyngitis	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Platelet count decreased	22.2% 4/18 • Number of events 5 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Rash acneiform	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Rash maculo-papular	55.6% 10/18 • Number of events 11 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Renal and urinary disorders Blood Urea Nitrogen elevated	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - (Other)	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Skin and subcutaneous tissue disorders Skin ulceration	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Small intestinal obstruction	11.1% 2/18 • Number of events 3 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Respiratory, thoracic and mediastinal disorders Sore throat	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Vascular disorders Thromboembolic event	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Infections and infestations Upper respiratory infection	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Infections and infestations Urinary tract infection	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Gastrointestinal disorders Vomiting	22.2% 4/18 • Number of events 6 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Weight loss	22.2% 4/18 • Number of events 5 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Chloride decreased	5.6% 1/18 • Number of events 2 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months
Investigations Platelet increased	5.6% 1/18 • Number of events 1 • Adverse event data collected during active 28 day cycle, treatment may continue for up to 24 months

Additional Information

Dr. Scott Kopetz/Associate Professor, GI Medical Oncology

The University of Texas MD Anderson Cancer Center, Clinical Research Operations

Phone: 713-792-2828

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60