The Combination of Palbociclib With ddEC-P as Neoadjuvant Therapy in Triple Negative Breast Cancer

Study Overview
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Brief Summary
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This study will look at effects the combination of palbociclib and dose-dense neoadjuvant chemotherapy may have on triple negative breast cancer tumours which have not yet been treated.

Detailed Description
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Patients will be randomized to one of two treatment arms (1:1 ratio). Dose-Dense neoadjuvant chemotherapy in the first 8 weeks of will be: epirubicin (90mg/m2) and cyclophosphamide (600mg/m2), followed by paclitaxel (80mg / m2) after 8 weeks, cycled every 14 days for total 8 cycles. Palbociclib will be administered orally as 125mg capsules, daily on a schedule of 3 weeks (21 days) on, 1 week (7 days) off of a 4 week [28 days] cycle. Arm I: Palbociclib combined with Dose-Dense neoadjuvant chemotherapy for total 16 weeks. Arm II: Placebo combined with Dose-Dense neoadjuvant chemotherapy for total 16 weeks. Note: Following completion of study therapy, surgery will be scheduled for 18-20 weeks post-randomization. Post-surgical treatment will be at the discretion of treating clinician, following postoperative pathology. After week 16 (end of study therapy) all patients should continue Palbociclib for one year. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

Official Title
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A Randomized Study Evaluating the Safety and Effects of the Combination of Palbociclib With Epirubicin and Cyclophosphamide Followed by Paclitaxel as Neoadjuvant Therapy in Triple Negative Breast Cancer

Conditions
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Breast Cancer, Breast Diseases, Breast Neoplasms

Intervention / Treatment
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* Drug: Palbociclib
* Drug: Placebo oral capsule
* Drug: Epirubicin
* Drug: Cyclophosphamide
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patients, 18 years ≤ age ≤ 80 years； Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 Histologically confirmed invasive breast cancer（early stage or locally advanced） HER2 negative (HER2+/- by IHC or FISH-) Hormone receptor (ER and PR) negative Cardiovascular: Baseline left ventricular ejection fraction (LVEF)≥55% measured by ECHO Signed informed consent form (ICF) Exclusion Criteria: Metastatic disease (Stage IV) or inflammatory breast cancer Previous or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin, Carcinoma in situ of the cervix. Clinically relevant cardiovascular disease: Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110); Unable or unwilling to swallow capsules.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Arm I: Palbociclib combined with Dose-Dense neoadjuvant chemotherapy for total 16 weeks. | Drug: Palbociclib<br>* Palbociclib will be administered orally as 125mg capsules, daily on a schedule of 3 weeks (21 days) on, 1 week (7 days) off of a 4 week [28 days] cycle.<br>Drug: Epirubicin<br>* Epirubicin (90mg/m2, D1) cycled every 14 days for the first 4 cycles.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide (600mg/m2, D1) cycled every 14 days for the first 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel (80mg/m2, D1) cycled every 14 days for the later 4 cycles.<br>|
| Placebo Comparator: Control group<br>Arm II: Placebo combined with Dose-Dense neoadjuvant chemotherapy for total 16 weeks. | Drug: Placebo oral capsule<br>* Placebo oral capsule will be administered orally as 125mg capsules, daily on a schedule of 3 weeks (21 days) on, 1 week (7 days) off of a 4 week [28 days] cycle.<br>Drug: Epirubicin<br>* Epirubicin (90mg/m2, D1) cycled every 14 days for the first 4 cycles.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide (600mg/m2, D1) cycled every 14 days for the first 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel (80mg/m2, D1) cycled every 14 days for the later 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR | Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery. | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DFS | Disease-free Survival | Following surgery until Year 3 | 
| ORR | Objective Response Rate (ORR) during neoadjuvant period | Through study completion, an average of 1 year. | 
| AEs | Number and severity of adverse events.Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). | baseline and weekly through 12 months after randomization |