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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo + Letrozole | Active Comparator | Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily |
|
| Ribociclib 600 mg + Letrozole | Experimental | Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily |
|
| Ribociclib 400 mg + Letrozole | Experimental | Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole | Drug | Nonsteroidal aromatase inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm. | 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. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Complete Cell Cycle Arrest at 2 Weeks Between Ribociclib Containing Arms (Combined) vs Letrozole Alone Arm. | Complete cell cycle arrest is defined as Ki67 at day 14 of < 2.7. | Day 14 of Cycle 1 |
| 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 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Qamar Khan, MD | University of Kansas Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States | ||
| City of Hope National Medical Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo + Letrozole | Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib |
| FG001 | Ribociclib 600 mg + Letrozole |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 24, 2018 |
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| Ribociclib | Drug | Oral cyclin-dependent kinase (CDK) inhibitor |
|
|
| Placebo | Drug | Placebo for ribociclib |
|
pCR is assciated with better outcomes in breast cancer |
| At Surgery (Days 8-15 of Cycle 6) |
| 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 |
| Duarte |
| California |
| 91010 |
| United States |
| Cancer Research Collaboration | Santa Ana | California | 92705 | United States |
| University of Miami Sylvester Comprehensive Cancer Center | Deerfield Beach | Florida | 33442 | United States |
| University of Kansas Cancer Center - West | Kansas City | Kansas | 66112 | United States |
| University of Kansas Cancer Center - Overland Park | Overland Park | Kansas | 66210 | United States |
| University of Kansas Cancer Center - Westwood | Westwood | Kansas | 66205 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| University of Kansas Cancer Center - South | Kansas City | Missouri | 64131 | United States |
| University of Kansas Cancer Center - North | Kansas City | Missouri | 64154 | United States |
| University of Kansas Cancer Center - Lee's Summit | Lee's Summit | Missouri | 64064 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| University of Wisconsin Carbone Cancer Center | Madison | Wisconsin | 53705 | United States |
Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor |
| FG002 | Ribociclib 400 mg + Letrozole | Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor |
| Received Treatment |
|
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo + Letrozole | Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib |
| BG001 | Ribociclib 600 mg + Letrozole | Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor |
| BG002 | Ribociclib 400 mg + Letrozole | Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median | Inter-Quartile Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Rate of PEPI Score 0 at Surgery Between Ribociclib Containing Arms (Combined) vs. Letrozole Alone Arm. | 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. | It was pre-specified as the primary endpoint in the Statistical Analysis Plan and the Study Protocol to compare Placebo therapy (Placebo + Letrozole) and combination therapy (Ribociclib + Letrozole). | Posted | Number | percentage of participants | 24 weeks |
|
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| |||||||||||||||||||||||||||||
| Secondary | Rate of Complete Cell Cycle Arrest at 2 Weeks Between Ribociclib Containing Arms (Combined) vs Letrozole Alone Arm. | Complete cell cycle arrest is defined as Ki67 at day 14 of < 2.7. | It was pre-specified as the primary endpoint in the Statistical Analysis Plan and the Study Protocol to compare single therapy (Placebo + Letrozole) and combination therapy (Ribociclib + Letrozole). | Posted | Number | percentage of participants | Day 14 of Cycle 1 |
|
| ||||||||||||||||||||||||||||||
| Secondary | 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 | pCR is assciated with better outcomes in breast cancer | Posted | Number | percentage of participants | At Surgery (Days 8-15 of Cycle 6) |
|
| |||||||||||||||||||||||||||||||
| Secondary | Clinical Complete Response Rate (cCR Rate): cCR Rate is Defined as the Proportion of Patients With no Residual Tumor by Clinical Exam | Not Posted | Post-surgery (Once in the first 4 weeks of post-op, then once every 6 months for 5 years post-op) | Participants | |||||||||||||||||||||||||||||||||||
| Secondary | 5 Year Relapse Free Survival (RFS) | Not Posted | 5 years post-treatment | Participants |
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo + Letrozole | Placebo randomized to 3 capsules/day 3 weeks on/1week off or 2 capsules/day continuous dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Placebo: Placebo for ribociclib | 0 | 37 | 3 | 37 | 19 | 37 |
| EG001 | Ribociclib 600 mg + Letrozole | Ribociclib 600 mg PO daily 21 days on/7 days off + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor | 0 | 41 | 25 | 41 | 21 | 41 |
| EG002 | Ribociclib 400 mg + Letrozole | Ribociclib 400 mg continuous daily dosing + Letrozole 2.5 mg PO daily Letrozole: Nonsteroidal aromatase inhibitor Ribociclib: Oral cyclin-dependent kinase (CDK) inhibitor | 1 | 41 | 20 | 41 | 23 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Electrocardiogram QT corrected interval prolonged | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hot flashes | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Creatinine increased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Electrocardiogram QT corrected interval prolonged | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| White blood cell decreased | Investigations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Localized edema | General disorders | MedDRA (10.0) | Non-systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Qamar Khan | UKansasMCRI | 9137106387 | qkhan@kumc.edu |
| Nov 13, 2025 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D000077289 | Letrozole |
| C000589651 | ribociclib |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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| Asian |
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| Other |
|
| Unknown |
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| White |
|
|
|