Trial of Neoadjuvant Endostar, Docetaxel and Epirubicin for Patients With Breast Cancer (CBCRT01)

Phase Ⅲ Trial of Neoadjuvant Recombinant Human Endostatin, Docetaxel and Epirubicin as First-Line Therapy in Patients With Breast Cancer

This study was designed to determine the efficacy and safety of neoadjuvant docetaxel and epirubicin (DE) with or without human recombinant endostatin (endostar) for breast cancer patients. The hypothesis of this protocol is that a combined angiogenesis inhibiting therapy to chemotherapy could further benefit breast cancer patients.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel and epirubicin; Drug: docetaxel and epirubicin plus endostatin

Detailed Description

This is a multicenter, prospective, randomized, controlled phase Ⅲ clinical trial. A total of 800 patients with core-biopsy confirmed breast cancer, stage ⅡA to ⅢC, and to be treated with neoadjuvant systemic therapy are eligible for entry into this study. Patients will be allocated randomly to two groups to receive either 3 cycles of neoadjuvant DE and endostar or 3 cycles of neoadjuvant DE. All cases receive mammography, contrast-enhanced ultrasound (CEUS), magnetic resonance angiography (MRA), and positron emission tomography (PET) scanning pre- and post-neoadjuvant therapy, and then undergo surgical resection. The primary endpoint is clinical/pathological response. The clinical response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed. The secondary endpoint is (1) the number of participants with adverse events, (2) quality of life scores, and (3) the number of adverse events reported during neoadjuvant therapy. In addition, the role of mammography, CEUS, MRA and PET for response evaluation, as well as the angiogenic profile and biological information involved in tumor response will be investigated.

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jianghao Chen, MD, PhD; Phone Number: 86-29-84775271; Email: chenjh@fmmu.edu.cn
• Study Contact Backup: Name: Qing Yao, MD; Phone Number: 86-29-84775271; Email: huanhuan@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital
      • Contact: Aidong Wen, MD; Phone Number: 8037 86-29-84775475; Email: adwen-2004@hotmail.com
      • Principal Investigator: Jianghao Chen, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed invasive breast cancer (core needle biopsy for breast cancer diagnosis and fine needle aspiration for lymph node metastasis diagnosis)
• Stage ⅡA-ⅢC
• Age 18-70
• ECOG performance status 0-2
• No evidence of distant metastasis
• No previous therapy
• Normal hematologic function
• left ventricular ejection fraction greater than 50 percent
• No abnormality of renal or liver function
• Written informed consent

Exclusion Criteria:

• With allergic constitution or possible allergic reflection to drugs to be used in this study
• Any concurrent uncontrolled medical or psychiatric disorder
• History of severe heart diseases, including congestive heart failure, unstable angina, uncontrolled arrhythmia, myocardial infarction, uncontrolled high blood pressure, or heart valve disease.
• History of bleeding diathesis
• Being pregnant or nursing

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: docetaxel and epirubicin; DE chemotherapy alone	Drug: docetaxel and epirubicin; docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle, totally 3 cycles; Other Names: Docetaxel, Sanofi-Aventis; Epirubicin, Pfizer
Experimental: docetaxel and epirubicin plus endostatin; chemotherapy plus endostatin	Drug: docetaxel and epirubicin plus endostatin; docetaxel 75mg/m2, IV (in the vein) on day 1 of each 21 day cycle; epirubicin 75 mg/m2, IV (in the vein) on day 1 of each 21 day cycle; endostatin 7.5mg/m2, IV (in the vein) on 1st to 14th days of each 21 day cycle; every 3 weeks, totally 3 cycles; Other Names: Endostatin, Simcere-Medgenn (No. S20050088)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical/pathological response	The clincial response will be evaluated according to RECIST criteria. The parameters of tumor metabolism and blood supply, as demonstrated by PET, MRA and CEUS, will be collected and analysed.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	The number of participants with adverse events will be recorded and analysed.	3 years
Quality of life	Quality of life is scored using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Questionnaire (QLQ30) at study entry and prior to surgery.	3 years
Number of adverse events reported during neoadjuvant therapy	The adverse events during neoadjuvant therapy will be graded using the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0.	3 years

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Jianghao Chen, MD, PhD, Xijing Hospital; Study Director: Ling Wang, MD, Xijing Hospital

Publications and helpful links

General Publications

• In our previous phase Ⅱ trial (NCT00604435), the combination of rh-endostatin with docetaxel and epirubicin chemotherapy resulted in a higher objective response rate without increased toxicity in breast cancer patients, as compared with chemotherapy alone. Our results have been accepted to report as General Poster in ASCO's 47th Annual Meeting in 2011. Wang L, Chen JH, Yao Q, et al. Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: efficacy and safety in a prospective, randomized, phase II study. 2011 ASCO Annual Meeting Proceedings, J Clin Oncol 2011; 29(15s): 112s.
• Chen J, Yao Q, Huang M, Wang B, Zhang J, Wang T, Ming Y, Zhou X, Jia Q, Huan Y, Wang J, Wang L. A randomized Phase III trial of neoadjuvant recombinant human endostatin, docetaxel and epirubicin as first-line therapy for patients with breast cancer (CBCRT01). Int J Cancer. 2018 May 15;142(10):2130-2138. doi: 10.1002/ijc.31217. Epub 2017 Dec 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: October 26, 2011
• First Submitted That Met QC Criteria: November 21, 2011
• First Posted (Estimate): November 24, 2011

Study Record Updates

• Last Update Posted (Estimate): November 24, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant chemotherapy; docetaxel; epirubicin; recombinant human endostatin (endostar)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Epirubicin; Endostatins
• Other Study ID Numbers: Endostar B-02; CBCRT01 (Other Grant/Funding Number: NNSF of China (No. 81172510, 30872514))