Breast Cancer
Conditions
Keywords
ER+, HER2-negative breast cancer, Stage II or III, Letrozole, Femara, Ribociclib, LEE011, Neo-adjuvant
Brief summary
The purpose of this study is to determine if ribociclib in combination with letrozole for 24 weeks as neoadjuvant endocrine therapy increases the proportion of women with Pre-operative Endocrine Prognostic Index (PEPI) score of 0 at surgery compared to patients treated with letrozole alone therefore allowing more patients excellent outcomes without chemotherapy.
Detailed description
Subjects will be randomized (1:1:1) to either letrozole plus placebo vs. letrozole plus continuous dosing of ribociclib vs. letrozole plus intermittent dosing (3-weeks-on/1-week-off) of ribociclib. The difference in clinical, pathologic and radiologic response as well as Pre-operative Endocrine Prognostic Index (PEPI) scores across the three treatments arms will be examined. Subjects will also be followed for 5 years post-treatment to determine if ribociclib in combination with letrozole for 24 weeks results in improved 5 year Relapse Free Survival (RFS) compared to letrozole alone.
Interventions
DRUGLetrozole
Nonsteroidal aromatase inhibitor
DRUGRibociclib
Oral cyclin-dependent kinase (CDK) inhibitor
DRUGPlacebo
Placebo for ribociclib
Sponsors
Qamar Khan
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Pathologically confirmed invasive breast cancer by core needle biopsy * Female subjects, age ≥ 18 years * Only postmenopausal women will be eligible. * Performance Status: Eastern Cooperative Oncology Group (ECOG) score 0-2 * Invasive breast cancer must be ER+ in ≥66 % of the cells or ER Allred score 6-8 * Invasive breast cancer must be HER2 negative. * Clinical Stage II or III (by clinical measurement and/or breast imaging) Key
Exclusion criteria
* Subjects meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm. | 24 weeks | The Preoperative Endocrine Prognostic Index (PEPI) score 0 is defined as: pT stage 0, 1, or 2 at surgery after 24 weeks of neoadjuvant therapy; negative axillary lymph nodes at surgey; Ki67 of ≤ 2.7 % at surgery; and tumor is ER+ at surgery. A PEPI score of 0 predicts a good outcome compare to PEPI score \>0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Complete Cell Cycle Arrest at 2 Weeks Between Ribociclib Containing Arms (Combined) vs Letrozole Alone Arm. | Day 14 of Cycle 1 | Complete cell cycle arrest is defined as Ki67 at day 14 of \< 2.7. |
| Pathologic Complete Response Rate (pCR Rate): pCR Rate is Defined as the Proportion of Patients With no Histologic Evidence of Invasive Tumor Cells in the Surgical Breast Specimen and the Axillary Lymph Nodes | At Surgery (Days 8-15 of Cycle 6) | pCR is assciated with better outcomes in breast cancer |
| Clinical Complete Response Rate (cCR Rate): cCR Rate is Defined as the Proportion of Patients With no Residual Tumor by Clinical Exam | Post-surgery (Once in the first 4 weeks of post-op, then once every 6 months for 5 years post-op) | — |
| 5 Year Relapse Free Survival (RFS) | 5 years post-treatment | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORQamar Khan, MD
University of Kansas Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Median Age | 65.8 years |
| Race/Ethnicity, Customized African American | 2 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants |
| Race/Ethnicity, Customized White | 28 Participants |
| Sex: Female, Male Female | 120 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 41 | 1 / 41 |
| other Total, other adverse events | 19 / 37 | 21 / 41 | 23 / 41 |
| serious Total, serious adverse events | 3 / 37 | 25 / 41 | 20 / 41 |
Outcome results
None listed