Trial Outcomes & Findings for TAK-228 Plus Tamoxifen in Patients With ER-Positive, HER2-negative Breast Cancer (NCT NCT02988986)

NCT ID: NCT02988986

Last Updated: 2021-09-22

Results Overview

Ki67 expression change from baseline to 6 weeks

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Baseline to 6 weeks

Results posted on

2021-09-22

Participant Flow

Participant milestones

Participant milestones
Measure	TAK-228 Plus Tamoxifen TAK-228 will be orally administered at 30 mg weekly for 16 weeks. Tamoxifen will be orally administered at 20 mg daily for 16 weeks. TAK-228: MTORC1/2 inhibitor Tamoxifen: Non-steroidal anti-estrogen
Overall Study STARTED	28
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

28 patients were enrolled in the study. 25 completed the entire study. 23 were evaluable for the primary endpoint. All 28 patients were evaluated for safety and toxicity.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAK-228 Plus Tamoxifen n=28 Participants TAK-228 will be orally administered at 30 mg weekly for 16 weeks. Tamoxifen will be orally administered at 20 mg daily for 16 weeks. TAK-228: MTORC1/2 inhibitor Tamoxifen: Non-steroidal anti-estrogen
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	52 years STANDARD_DEVIATION 11.6 • n=93 Participants • 28 patients were enrolled in the study. 25 completed the entire study. 23 were evaluable for the primary endpoint. All 28 patients were evaluated for safety and toxicity.
Sex: Female, Male Female	28 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants
Race (NIH/OMB) More than one race	4 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	28 Participants n=93 Participants
Stage I-III ER-positive, HER-2 negative breast cancer	28 Participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline to 6 weeks

Population: Change in baseline Ki67 expression at 6 weeks

Ki67 expression change from baseline to 6 weeks

Outcome measures

Outcome measures
Measure	TAK-228 Plus Tamoxifen n=23 Participants TAK-228 will be orally administered at 30 mg weekly for 16 weeks. Tamoxifen will be orally administered at 20 mg daily for 16 weeks. TAK-228: MTORC1/2 inhibitor Tamoxifen: Non-steroidal anti-estrogen
Ki67 Expression Ki67 expression at baseline	15 Percentage of cells with Ki67 expression Interval 10.0 to 25.0
Ki67 Expression Ki67 expression at 6 weeks	10 Percentage of cells with Ki67 expression Interval 2.0 to 38.0

SECONDARY outcome

Timeframe: 16 weeks

Evaluate the number of participants meeting certain PEPI score after treatment with TAK-228 plus tamoxifen. PEPI score of 0 indicates low risk of disease recurrence (better outcome) PEPI score of 1-3 indicates intermediate risk of of disease recurrence (worse outcome) PEPI score of \>4 indicates high risk of of disease recurrence (worst outcome)

Outcome measures

Outcome measures
Measure	TAK-228 Plus Tamoxifen n=21 Participants TAK-228 will be orally administered at 30 mg weekly for 16 weeks. Tamoxifen will be orally administered at 20 mg daily for 16 weeks. TAK-228: MTORC1/2 inhibitor Tamoxifen: Non-steroidal anti-estrogen
Number of Participants Meeting Certain Preoperative Endocrine Prognostic Index (PEPI) PEPI score of 0	0 Participants
Number of Participants Meeting Certain Preoperative Endocrine Prognostic Index (PEPI) PEPI score of 1-3	6 Participants
Number of Participants Meeting Certain Preoperative Endocrine Prognostic Index (PEPI) PEPI score of >4	15 Participants

SECONDARY outcome

Timeframe: 16 weeks

Pathologic complete response was defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0 ypN0 or ypTis ypN0 in the current American Joint Committee on Cancer staging system).

Outcome measures

Outcome measures
Measure	TAK-228 Plus Tamoxifen n=23 Participants TAK-228 will be orally administered at 30 mg weekly for 16 weeks. Tamoxifen will be orally administered at 20 mg daily for 16 weeks. TAK-228: MTORC1/2 inhibitor Tamoxifen: Non-steroidal anti-estrogen
Number of Participants With Pathological Complete Response (pCR)	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Measure plasma concentrations of TAK-228 plus tamoxifen over time

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Assess the correlation between change in Ki67 expression and pCR to TAK-228 plus tamoxifen

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Assess correlation between tumor mutational status and response to TAK-228 plus tamoxifen

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 16 weeks

Assess the correlation between change in mTOR expression and pCR to TAK-228 plus tamoxifen

Outcome measures

Outcome data not reported

Adverse Events

TAK-228 and Tamoxifen

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TAK-228 and Tamoxifen n=28 participants at risk 20 mg p.o QW x16 weeks
Endocrine disorders hyperglycemia	3.6% 1/28 • Number of events 1 • Up to 16 weeks

Other adverse events

Other adverse events
Measure	TAK-228 and Tamoxifen n=28 participants at risk 20 mg p.o QW x16 weeks
Gastrointestinal disorders Nausea	100.0% 28/28 • Number of events 28 • Up to 16 weeks

Additional Information

Dr. Jenny Chang, Director of Houston Methodist Cancer Center

Houston Methodist Hospital

Phone: 713-441-0681

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place