Description:
The purpose of the study was to determine whether treatment with a PI3K inhibitor plus
letrozole led to an increase in pathologic clinical response and Objective Response Rate
compared to treatment with placebo plus letrozole in patients with Breast cancer.
Title
- Brief Title: Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
- Official Title: A Phase II Randomized, Double-blind Placebo Controlled, Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women With Hormone Receptor-positive HER2-negative Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
CBYL719A2201
- SECONDARY ID:
2013-001862-41
- NCT ID:
NCT01923168
Conditions
Interventions
Drug | Synonyms | Arms |
---|
alpelisib | BYL719 | Alpelisib + Letrozole |
buparlisib | BKM120 | Buparlisib + Letrozole |
Placebo | BYL719 Placebo, BKM120 Placebo | Placebo + Letrozole |
Purpose
The purpose of the study was to determine whether treatment with a PI3K inhibitor plus
letrozole led to an increase in pathologic clinical response and Objective Response Rate
compared to treatment with placebo plus letrozole in patients with Breast cancer.
Trial Arms
Name | Type | Description | Interventions |
---|
Alpelisib + Letrozole | Experimental | Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. | |
Buparlisib + Letrozole | Experimental | Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily. | |
Placebo + Letrozole | Placebo Comparator | Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily. | |
Eligibility Criteria
Inclusion Criteria:
1. Patient is an adult, female ≥ 18 years old at the time of informed consent
2. Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
3. Patient is postmenopausal.
4. Patient has T1c-T3, any N, M0, operable breast cancer
5. Patients must have measurable disease
6. Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67
level.
7. Patient has estrogen-receptor and/or progesterone positive breast cancer as per local
laboratory testing
8. Patient has HER2 negative breast cancer defined as a negative in situ hybridization
test or an IHC status of 0 or 1+ as per local laboratory testing
Exclusion Criteria:
1. Patient has locally recurrent or metastatic disease
2. Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy,
immunotherapy) or radiotherapy for current breast cancer disease before randomization.
3. Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes
mellitus
4. History of acute pancreatitis within 1 year of study entry
5. Uncontrolled hypertension
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort |
Time Frame: | After 24 weeks of treatment |
Safety Issue: | |
Description: | Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate. |
Secondary Outcome Measures
Measure: | pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Mutant Cohort Based on ctDNA |
Time Frame: | After 24 weeks of treatment |
Safety Issue: | |
Description: | pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment |
Measure: | pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Wild-type Cohort Based on ctDNA |
Time Frame: | After 24 weeks of treatment |
Safety Issue: | |
Description: | pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment |
Measure: | Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort |
Time Frame: | After 24 weeks of treatment |
Safety Issue: | |
Description: | Breast conserving surgery is defined for participants who underwent surgery and did not have a mastectomy. The row "no surgery" provides the number of patients who did not undergo surgery at all for various reasons. |
Measure: | Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort |
Time Frame: | After 24 weeks of treatment |
Safety Issue: | |
Description: | Breast conserving surgery is defined as the percentage of participants with no mastectomy following completion of 24 weeks of treatment. Breast conserving surgery is defined for participants who underwent surgery and did not have a mastectomy. The row "no surgery" provides the number of patients who did not undergo surgery at all for various reasons. |
Measure: | Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR |
Time Frame: | Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) |
Safety Issue: | |
Description: | Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR |
Measure: | Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR |
Time Frame: | Baseline, Cycle 1 Day 15 (each cycle is 28 days ) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) |
Safety Issue: | |
Description: | Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR. |
Measure: | Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR |
Time Frame: | Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) |
Safety Issue: | |
Description: | Association between pCR and changes in Ki67 from baseline for alpelisib vs. placebo - PIK3CA wild-type cohort: responders as per pCR |
Measure: | Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR |
Time Frame: | Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment) |
Safety Issue: | |
Description: | Association between pCR and changes in Ki67 from baseline for alpelisib vs. placebo - PIK3CA wild-type cohort: non-responders as per pCR |
Measure: | Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort |
Time Frame: | At the time of surgery (expected after 24 weeks of treatment) |
Safety Issue: | |
Description: | Preoperative endocrine prognostic index (PEPI) response as per central assessment for alpelisib vs. placebo - PIK3CA mutant cohort. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and ER status of the surgical specimen (Ellis et al, Contemp Clin Trials 2008). The PEPI score ranges from 0 to to 12, and a higher score means a worse outcome. PEPI response is defined as a PEPI score of 0. |
Measure: | Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort |
Time Frame: | At the time of surgery (expected after 24 weeks of treatment) |
Safety Issue: | |
Description: | Preoperative endocrine prognostic index (PEPI) response as per central assessment for alpelisib vs. placebo - PIK3CA wild-type cohort. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and ER status of the surgical specimen (Ellis et al, Contemp Clin Trials 2008). The PEPI score ranges from 0 to to 12, and a higher score means a worse outcome. PEPI response is defined as a PEPI score of 0. |
Measure: | Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1 |
Time Frame: | 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for alpelisib plasma concentration |
Measure: | Alpelisib PK Parameter: Cmax at Cycle 1 Day 1 |
Time Frame: | Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for alpelisib plasma concentration |
Measure: | Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1 |
Time Frame: | Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for alpelisib plasma concentration |
Measure: | Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1 |
Time Frame: | 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for alpelisib plasma concentration |
Measure: | Alpelisib PK Parameter: Cmax at Cycle 4 Day 1 |
Time Frame: | Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for alpelisib plasma concentration |
Measure: | Alpelisib PK Parameter: Tmax at Cycle 4 Day 1 |
Time Frame: | Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for alpelisib plasma concentration |
Measure: | Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1 |
Time Frame: | 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for Letrozole plasma concentration |
Measure: | Letrozole PK Parameter: Cmax at Cycle 1 Day 1 |
Time Frame: | Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for letrozole plasma concentration |
Measure: | Letrozole PK Parameter: Tmax at Cycle 1 Day 1 |
Time Frame: | Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for letrozole plasma concentration |
Measure: | Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1 |
Time Frame: | 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for Letrozole plasma concentration |
Measure: | Letrozole PK Parameter: Cmax at Cycle 4 Day 1 |
Time Frame: | Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for letrozole plasma concentration |
Measure: | Letrozole PK Parameter: Tmax at Cycle 4 Day 1 |
Time Frame: | Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for letrozole plasma concentration |
Measure: | Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1 |
Time Frame: | 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for Buparlisib plasma concentration |
Measure: | Buparlisib PK Parameter: Cmax at Cycle 1 Day 1 |
Time Frame: | Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for buparlisib plasma concentration |
Measure: | Buparlisib PK Parameter: Tmax at Cycle 1 Day 1 |
Time Frame: | Cycle 1 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for buparlisib plasma concentration |
Measure: | Buparlisib PK Parameter: AUClast at Cycle 4 Day 1 |
Time Frame: | 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for Buparlisib plasma concentration |
Measure: | Buparlisb PK Parameter: Cmax at Cycle 4 Day 1 |
Time Frame: | Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for buparlisib plasma concentration |
Measure: | Buparlisib PK Parameter: Tmax at Cycle 4 Day 1 |
Time Frame: | Cycle 4 Day 1 (each cycle is 28 days) |
Safety Issue: | |
Description: | Summary of primary PK parameters for buparlisib plasma concentration |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- BYL719
- alpelisib
- Breast Cancer
- BKM120
- buparlisib
- Pathological Complete Response
- neoadjuvant
- hormone receptor-positive
- HER2 negative
- Objective Response Rate
Last Updated
September 14, 2018