Letrozole and CDK 4/6 Inhibitor for ER Positive, HER2 Negative Breast Cancer in Postmenopausal Women

Study Overview
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Brief Summary
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This is a phase II study evaluating the efficacy and safety of the pre-operative use of letrozole plus PD 0332991 (combination therapy)

Official Title
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Phase II Neoadjuvant Study of Letrozole in Combination With PD0332991 (Oral CDK 4/6 Inhibitor) for ER Positive, HER2 Negative Breast Cancer in Postmenopausal Women

Conditions
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ER Positive, HER2 Negative Breast Cancer

Intervention / Treatment
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* Drug: Letrozole, PD 0332991


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women Primary tumor greater than 2 cm in diameter Histologically proven invasive breast cancer Positive estrogen receptor Negative HER-2 receptor ECOG performance status ≤ 1 or Karnofsky performance status ≥ 70% Laboratory values must be follows: Absolute neutrophil count ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9 g/dL; Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); Serum Creatinine ≤ 1.5 × ULN; Alkaline phosphatase ≤ 2 × ULN; AST and ALT ≤ 2 × ULN; Normal finding of ECG - QTc ≤ 470 msec (based on the mean value of the triplicate ECGs); Left ventricular ejection fraction (LVEF) ≥ 60%. Able to give written informed consent form Able to follow prescription instructions reasonably well Exclusion Criteria: Male Severe psychiatric disorder Prior history of other malignancy within 5 years of study entry, aside from basal cell carcinoma or the skin or carcinoma-in-situ of the uterine cervix Locally advanced breast cancer (T3N1 or Any T4 or Any N2, N3), or distant metastasis Multifocal or multicentric breast cancer except that the largest lesion is greater than 2cm Major surgery within 3 weeks of first study treatment Current use or anticipated need for: Food or drugs that are known strong CYP3A4 inhibitors; drugs that are known strong CYP3A4 inducers Severe cardiovascular diseases in the previous 6 months Active inflammatory bowel disease or chronic diarrhea Renal Impairment Poor adrenal function Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function) Known human immunodeficiency virus infection Known hypersensitivity to anti-aromatase drugs or any cell cycle inhibitor Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole plus PD 0332991<br>Drug: Letrozole 2.5mg/d for 16 weeks before surgery plus PD 0332991 (CDK-4/6 inhibitor) 125 mg/d for 3 out of 4 weeks in repeated cycles for 16 weeks before surgery | Drug: Letrozole, PD 0332991<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rates |  | Every 4 weeks before surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events |  | Continuous during the study, up to 28 days after the last treatment |