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

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

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Breast Neoplasms; Breast Diseases
• Intervention / Treatment: Drug: Palbociclib; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Placebo oral capsule

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Arm I: Palbociclib combined with Dose-Dense neoadjuvant chemotherapy for total 16 weeks.	Drug: Palbociclib; 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.; Drug: Epirubicin; Epirubicin (90mg/m2, D1) cycled every 14 days for the first 4 cycles.; Drug: Cyclophosphamide; Cyclophosphamide (600mg/m2, D1) cycled every 14 days for the first 4 cycles.; Drug: Paclitaxel; Paclitaxel (80mg/m2, D1) cycled every 14 days for the later 4 cycles.
Placebo Comparator: Control group; Arm II: Placebo combined with Dose-Dense neoadjuvant chemotherapy for total 16 weeks.	Drug: Epirubicin; Epirubicin (90mg/m2, D1) cycled every 14 days for the first 4 cycles.; Drug: Cyclophosphamide; Cyclophosphamide (600mg/m2, D1) cycled every 14 days for the first 4 cycles.; Drug: Paclitaxel; Paclitaxel (80mg/m2, D1) cycled every 14 days for the later 4 cycles.; Drug: Placebo oral capsule; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): November 30, 2020

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): December 7, 2018
• Last Update Submitted That Met QC Criteria: December 6, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Neoplasms; Triple Negative Breast Neoplasms; Breast Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Epirubicin; Palbociclib
• Other Study ID Numbers: PECP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No