Trial Outcomes & Findings for Presurgical Treatment With Letrozole in Patients With Early-stage Breast Cancer. (NCT NCT02010021)

NCT ID: NCT02010021

Last Updated: 2019-01-17

Results Overview

The Primary Endpoint is to determine the effect of ex vivo mTORC1 inhibition with everolimus (RAD001) on IRS-1/PI3K/AKT pathway activation (as measured by phospho-AKT-T308 and phospho-AKT-S473) in ER+/human epidermal growth factor receptor 2 (HER2)- breast tumors treated with presurgical letrozole compared to ER+/HER2- breast tumors not treated with presurgical therapy.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 17 participants
• Primary outcome timeframe: baseline and surgery, approximately 30 days
• Results posted on: 2019-01-17

Participant Flow

Participant milestones

Measure	No Drug Treatment Post-menopausal women with stage I-III breast cancer with surgical resection of tumor and tumor tissue will be used to study cell growth signaling pathways ex-vivo.	Letrozole-presurgical Patients received Letrozole for 10-21 days prior to surgical resection of tumor tissue. This tissue was used ex-vivo to study cell growth signaling pathway. The results will be compared to arm of the study with no intervention.
Overall Study STARTED	10	7
Overall Study COMPLETED	10	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Presurgical Treatment With Letrozole in Patients With Early-stage Breast Cancer.

Baseline characteristics by cohort

Measure	No Drug Treatment n=10 Participants Post-menopausal women with stage I-III breast cancer with surgical resection of tumor and tumor tissue will be used to study cell growth signaling pathways ex-vivo.	Letrozole-presurgical n=7 Participants Patients received Letrozole for 10-21 days prior to surgical resection of tumor tissue. This tissue was used ex-vivo to study cell growth signaling pathway. The results will be compared to arm of the study with no intervention.	Total n=17 Participants Total of all reporting groups
Age, Continuous	65.6 years n=5 Participants	64.9 years n=7 Participants	65.3 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White, not Hispanic	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and surgery, approximately 30 days

The Primary Endpoint is to determine the effect of ex vivo mTORC1 inhibition with everolimus (RAD001) on IRS-1/PI3K/AKT pathway activation (as measured by phospho-AKT-T308 and phospho-AKT-S473) in ER+/human epidermal growth factor receptor 2 (HER2)- breast tumors treated with presurgical letrozole compared to ER+/HER2- breast tumors not treated with presurgical therapy.

Outcome measures

Measure	No Drug Treatment n=10 Participants Post-menopausal women with stage I-III breast cancer with surgical resection of tumor and tumor tissue will be used to study cell growth signaling pathways ex-vivo.	Letrozole-presurgical n=7 Participants Patients received Letrozole for 10-21 days prior to surgical resection of tumor tissue. This tissue was used ex-vivo to study cell growth signaling pathway. The results will be compared to arm of the study with no intervention.
Change in Insulin Receptor Substrate 1 (IRS-1) / Phosphoinositide 3-kinase (PI3K) / Serine-threonine Protein Kinase (AKT) Pathway Activation phospho-AKT-T308	388 % change Standard Deviation 623	-10 % change Standard Deviation 38
Change in Insulin Receptor Substrate 1 (IRS-1) / Phosphoinositide 3-kinase (PI3K) / Serine-threonine Protein Kinase (AKT) Pathway Activation phospho-AKT-S473	157 % change Standard Deviation 35	135 % change Standard Deviation 91

SECONDARY outcome

Timeframe: baseline and surgery, approximately 30 days

The Secondary Endpoint is to compare tumor cell proliferation as measured with the Ki-67 assay in breast cancer specimens taken before and at the time of surgery, comparing specimens of patients treated with presurgical letrozole and specimens of patients who did not receive presurgical letrozole. The secondary endpoint is Ki67 score, as determined by the percentage of Ki67+ tumor cells identified by immunohistochemistry.

Whole slides were scanned at 40x (Aperio AT2, Leica Biosystems), and automated Ki67 analysis (percent positive nuclei) was determined using the Aperio ImageScope (v12.3.1.60002, Leica Biosystems) nuclear v9 algorithm. As recommended by the International Ki67 in Breast Cancer Working Group, 3 high-power microscopic fields were selected for analysis to represent the spectrum of staining present on the whole tissue section, and a minimum of 500 malignant invasive cells were score

Outcome measures

Measure	No Drug Treatment n=10 Participants Post-menopausal women with stage I-III breast cancer with surgical resection of tumor and tumor tissue will be used to study cell growth signaling pathways ex-vivo.	Letrozole-presurgical n=7 Participants Patients received Letrozole for 10-21 days prior to surgical resection of tumor tissue. This tissue was used ex-vivo to study cell growth signaling pathway. The results will be compared to arm of the study with no intervention.
Percentage of Ki67 Score	-7.462 change in % of Ki67+ tumor cells Interval -31.025 to 7.575	-21.309 change in % of Ki67+ tumor cells Interval -42.175 to -2.875

Adverse Events

No Drug Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Letrozole-presurgical

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Gary N. Schwartz, MD

Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center

Phone: (603) 653-6181

Email: gary.n.schwartz@hitchcock.org

Results disclosure agreements

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