Trial Outcomes & Findings for Akt Inhibitor MK-2206 and Anastrozole With or Without Goserelin Acetate in Treating Patients With Stage II-III Breast Cancer (NCT NCT01776008)

Last Updated: 2018-05-08

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

At time of surgery (up to 3 weeks after 4, 28-day cycles)

Results posted on

2018-05-08

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) 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 Study STARTED	16
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) 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 Study ineligible	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) n=16 Participants 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.
Age, Continuous	57.5 years n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: At time of surgery (up to 3 weeks after 4, 28-day cycles)

Population: All patients beginning protocol therapy and evaluable for primary endpoint were included in this analysis.

Outcome measures

Outcome measures
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) n=16 Participants 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.
Pathological Complete Response Rate	0 participants

SECONDARY outcome

Timeframe: Baseline to end of Cycle 4 (28 day cycles)

Population: Due to missing bi-dimensional measurements, clinical response could not be determined.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to end of Cycle 4 (28 day cycles)

Population: All patients that registered and began neoadjuvant treatment were included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) n=16 Participants 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.
Incidence of Adverse Events, Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Grade 3+ Adverse Event	6 Participants
Incidence of Adverse Events, Based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Grade 4+ Adverse Event	2 Participants

SECONDARY outcome

Timeframe: Baseline and completion of cycle 4 (28 day cycles)

Population: Due to missing pre-surgical scans, this endpoint could not be evaluated.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: Data was not collected

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: Data was not collected.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: Data was not collected.

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%.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline, following 4 weeks of anastrozole alone, day 1 of course 3, and at pre-surgery

Population: Data was not collected.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 weeks following the last dose of Akt inhibitor MK-2206

Population: Data was not collected.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (MK2206, Anastrozole, Goserelin Acetate)

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) n=16 participants at risk 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.
Investigations Alanine aminotransferase increased	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Investigations Aspartate aminotransferase increased	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.

Other adverse events

Other adverse events
Measure	Treatment (MK2206, Anastrozole, Goserelin Acetate) n=16 participants at risk 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.
Cardiac disorders Sinus bradycardia	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Gastrointestinal disorders Diarrhea	6.2% 1/16 • Number of events 3 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Gastrointestinal disorders Dry mouth	6.2% 1/16 • Number of events 2 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Gastrointestinal disorders Mucositis oral	12.5% 2/16 • Number of events 3 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Gastrointestinal disorders Nausea	37.5% 6/16 • Number of events 9 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Gastrointestinal disorders Oral dysesthesia	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
General disorders Fatigue	87.5% 14/16 • Number of events 42 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
General disorders Fever	12.5% 2/16 • Number of events 2 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Infections and infestations Infections and infestations - Other, specify	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Metabolism and nutrition disorders Anorexia	31.2% 5/16 • Number of events 9 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Metabolism and nutrition disorders Hyperglycemia	75.0% 12/16 • Number of events 34 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Metabolism and nutrition disorders Serum potassium decreased	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Nervous system disorders Dysgeusia	6.2% 1/16 • Number of events 3 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Nervous system disorders Headache	12.5% 2/16 • Number of events 5 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Psychiatric disorders Agitation	6.2% 1/16 • Number of events 3 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Psychiatric disorders Libido decreased	6.2% 1/16 • Number of events 2 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Psychiatric disorders Libido increased	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Psychiatric disorders Psychiatric disorders - Other, specify	6.2% 1/16 • Number of events 1 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Reproductive system and breast disorders Vaginal dryness	6.2% 1/16 • Number of events 3 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Skin and subcutaneous tissue disorders Dry skin	43.8% 7/16 • Number of events 20 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Skin and subcutaneous tissue disorders Pruritus	43.8% 7/16 • Number of events 15 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Skin and subcutaneous tissue disorders Rash maculo-papular	75.0% 12/16 • Number of events 25 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Vascular disorders Hot flashes	12.5% 2/16 • Number of events 4 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Vascular disorders Hypertension	6.2% 1/16 • Number of events 2 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.
Vascular disorders Vascular disorders - Other, specify	12.5% 2/16 • Number of events 3 • Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery. Adverse Events were collected after every cycle of treatment (28 day cycles) and up to 60 days after surgery.

Additional Information

Cynthia Ma, M.D., Ph.D.

Washington University School of Medicine

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60