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Trial record 30 of 50 for:    MK-2206

Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer

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ClinicalTrials.gov Identifier: NCT01776008
Recruitment Status : Terminated (Study did not pass Stage 1 interim analysis.)
First Posted : January 25, 2013
Results First Posted : May 8, 2018
Last Update Posted : May 8, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Estrogen Receptor Positive
HER2/Neu Negative
Recurrent Breast Carcinoma
Stage IIA Breast Cancer
Stage IIB Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Interventions Drug: Akt Inhibitor MK2206
Drug: Anastrozole
Drug: Goserelin Acetate
Other: Laboratory Biomarker Analysis
Procedure: Neoadjuvant Therapy
Other: Pharmacological Study
Procedure: Therapeutic Conventional Surgery
Enrollment 16

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 16
Completed 14
Not Completed 2
Reason Not Completed
ineligible             2
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
All patients registering were included in baseline description.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants
57.5
(40 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
16
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 16 participants
16
 100.0%
1.Primary Outcome
Title Pathological Complete Response Rate
Hide Description Any woman whose Ki67 value ≤10% on cycle 1 day 17 of combination treatment who does not receive alternative treatment prior to surgery and has no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes is considered to have a pathological complete response (pCR). A ninety percent confidence interval for the true pathologic complete response rate will be calculated using the Duffy-Santer approach.
Time Frame At time of surgery (up to 3 weeks after 4, 28-day cycles)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients beginning protocol therapy and evaluable for primary endpoint were included in this analysis.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: participants
0
2.Secondary Outcome
Title Clinical Response Rate
Hide Description The Clinical response rate is estimated by the number of patients whose disease meets the WHO criteria of complete or partial response based on physical examination divided by the total number of eligible patients. Complete Response (CR) is defined as the disappearance of all known disease based on measurements taken at the completion of neo-adjuvant therapy. Partial Response (PR) is defined as a 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy. A ninety percent confidence interval for the true clinical response rate will be calculated using the Duffy-Santer approach.
Time Frame Baseline to end of Cycle 4 (28 day cycles)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to missing bi-dimensional measurements, clinical response could not be determined.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Incidence of Adverse Events, Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Hide Description The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. For this endpoint, we are reporting the number of patients that reported a grade 3 or higher graded adverse event during neoadjuvent treatment. A complete list of all reported adverse events is in the Adverse Events section of the report.
Time Frame Baseline to end of Cycle 4 (28 day cycles)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients that registered and began neoadjuvant treatment were included in this analysis.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 16
Measure Type: Count of Participants
Unit of Measure: Participants
Grade 3+ Adverse Event
6
  37.5%
Grade 4+ Adverse Event
2
  12.5%
4.Secondary Outcome
Title Radiological Response Rate
Hide Description The Clinical response rate is estimated by the number of patients whose disease meets the WHO criteria of complete or partial response based on radiographic evaluation (mammogram or ultrasound) divided by the total number of eligible patients. Complete Response (CR) is defined as the disappearance of all known disease based on measurements taken at the completion of neo-adjuvant therapy. Partial Response (PR) is defined as a 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy. A ninety percent confidence interval for the true clinical response rate will be calculated using the Duffy-Santer approach.
Time Frame Baseline and completion of cycle 4 (28 day cycles)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to missing pre-surgical scans, this endpoint could not be evaluated.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Other Pre-specified Outcome
Title Change in Ki67 Levels
Hide Description [Not Specified]
Time Frame From 2 weeks of combination therapy with Akt inhibitor MK2206 and anastrozole (day 17 of course 1) to after 4 weeks of treatment with anastrozole alone
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data was not collected
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Other Pre-specified Outcome
Title Percent Change in the Apoptotic Index
Hide Description [Not Specified]
Time Frame From 2 weeks of combination therapy with Akt inhibitor MK2206 and anastrozole (day 17 of course 1) to after 4 weeks of treatment with anastrozole alone
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data was not collected.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Other Pre-specified Outcome
Title Proportion of Patients Whose Ki67 Values is at Most 10%
Hide Description A 95% binomial confidence intervals will be constructed for the true proportion of patients whose pre Akt inhibitor MK2206 ki67 value is at most 10% as well as for the true proportion of patients with a C1D17 Ki67 value that is at most 10% among those patients whose pre Akt inhibitor MK2206 Ki67 was more than 10%.
Time Frame From 2 weeks of combination therapy with Akt inhibitor MK2206 and anastrozole (day 17 of course 1) to after 4 weeks of treatment with anastrozole alone
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data was not collected.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Other Pre-specified Outcome
Title Serum Estradiol Levels
Hide Description [Not Specified]
Time Frame At baseline, following 4 weeks of anastrozole alone, day 1 of course 3, and at pre-surgery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data was not collected.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
9.Other Pre-specified Outcome
Title The Pharmacodynamic Effect of Akt Inhibitor MK2206 in Combination With Anastrozole on the PI3K Pathway Activities, Assessed by Phosphoroproteomics and Immunohistochemistry Analysis on Serial Tumor Biopsies
Hide Description [Not Specified]
Time Frame Up to 3 weeks following the last dose of Akt inhibitor MK-2206
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data was not collected.
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description:
Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Adverse Event Reporting Description Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
 
Arm/Group Title Treatment (MK2206, Anastrozole, Goserelin Acetate)
Hide Arm/Group Description Patients receive 150 mg Akt inhibitor MK-2206 PO on days 2, 9, 16, and 23; 1 mg anastrozole PO daily on days 1-28; and 3.6 mg goserelin acetate SC on day 1 (premenopausal patients only). Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Treatment (MK2206, Anastrozole, Goserelin Acetate)
Affected / at Risk (%)
Total   0/16 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (MK2206, Anastrozole, Goserelin Acetate)
Affected / at Risk (%) # Events
Total   1/16 (6.25%)    
Investigations   
Alanine aminotransferase increased  1  1/16 (6.25%)  1
Aspartate aminotransferase increased  1  1/16 (6.25%)  1
1
Term from vocabulary, MedDRA 12
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (MK2206, Anastrozole, Goserelin Acetate)
Affected / at Risk (%) # Events
Total   16/16 (100.00%)    
Cardiac disorders   
Sinus bradycardia  1  1/16 (6.25%)  1
Gastrointestinal disorders   
Diarrhea  1  1/16 (6.25%)  3
Dry mouth  1  1/16 (6.25%)  2
Mucositis oral  1  2/16 (12.50%)  3
Nausea  1  6/16 (37.50%)  9
Oral dysesthesia  1  1/16 (6.25%)  1
General disorders   
Fatigue  1  14/16 (87.50%)  42
Fever  1  2/16 (12.50%)  2
Infections and infestations   
Infections and infestations - Other, specify  1  1/16 (6.25%)  1
Metabolism and nutrition disorders   
Anorexia  1  5/16 (31.25%)  9
Hyperglycemia  1  12/16 (75.00%)  34
Serum potassium decreased  1  1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/16 (6.25%)  1
Myalgia  1  1/16 (6.25%)  1
Nervous system disorders   
Dysgeusia  1  1/16 (6.25%)  3
Headache  1  2/16 (12.50%)  5
Psychiatric disorders   
Agitation  1  1/16 (6.25%)  3
Libido decreased  1  1/16 (6.25%)  2
Libido increased  1  1/16 (6.25%)  1
Psychiatric disorders - Other, specify  1  1/16 (6.25%)  1
Reproductive system and breast disorders   
Vaginal dryness  1  1/16 (6.25%)  3
Skin and subcutaneous tissue disorders   
Dry skin  1  7/16 (43.75%)  20
Pruritus  1  7/16 (43.75%)  15
Rash maculo-papular  1  12/16 (75.00%)  25
Vascular disorders   
Hot flashes  1  2/16 (12.50%)  4
Hypertension  1  1/16 (6.25%)  2
Vascular disorders - Other, specify  1  2/16 (12.50%)  3
1
Term from vocabulary, MedDRA 12
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Cynthia Ma, M.D., Ph.D.
Organization: Washington University School of Medicine
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01776008     History of Changes
Other Study ID Numbers: NCI-2013-00080
NCI-2013-00080 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1139
MC1139 ( Other Identifier: Mayo Clinic Cancer Center P2C )
9170 ( Other Identifier: CTEP )
N01CM00071 ( U.S. NIH Grant/Contract )
N01CM00099 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: January 23, 2013
First Posted: January 25, 2013
Results First Submitted: September 7, 2017
Results First Posted: May 8, 2018
Last Update Posted: May 8, 2018