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

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).

• Palbociclib (Drug): 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.
• Placebo oral capsule (Drug): 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.
• Epirubicin (Drug): Epirubicin (90mg/m2, D1) cycled every 14 days for the first 4 cycles.
• Cyclophosphamide (Drug): Cyclophosphamide (600mg/m2, D1) cycled every 14 days for the first 4 cycles.
• Paclitaxel (Drug): Paclitaxel (80mg/m2, D1) cycled every 14 days for the later 4 cycles.

Primary outcomes

• pCR [Through study completion, an average of 1 year.]: Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery.

Secondary outcomes

• DFS [Following surgery until Year 3]: Disease-free Survival
• ORR [Through study completion, an average of 1 year.]: Objective Response Rate (ORR) during neoadjuvant period
• AEs [baseline and weekly through 12 months after randomization]: 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).

Sex: Female, ages: 18 Years to 80 Years, accepts healthy volunteers

Inclusion Criteria:

1. female patients, 18 years ≤ age ≤ 80 years；
2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
3. Histologically confirmed invasive breast cancer（early stage or locally advanced）
4. HER2 negative (HER2+/- by IHC or FISH-)
5. Hormone receptor (ER and PR) negative
6. Cardiovascular: Baseline left ventricular ejection fraction (LVEF)≥55% measured by ECHO
7. Signed informed consent form (ICF)

Exclusion Criteria:

1. Metastatic disease (Stage IV) or inflammatory breast cancer
2. 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.
3. Clinically relevant cardiovascular disease: Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110);
4. Unable or unwilling to swallow capsules.

• Ding Xiaowen, DR., Principal investigator, Zhejiang Cancer Hospital