Weekly Paclitaxel and Cisplatin to Treat Hormone Receptor Positive and Triple Negative Breast Cancer Patients (SHPD002)

A Prospective, Randomized, Open-label Comparison of Preoperative Weekly Paclitaxel and Cisplatin With or Without Endocrine Therapy in Patients With Operable Hormone Receptor Positive and Triple Negative Locally Advanced Breast Cancer

The investigators hypothesize that paclitaxel combined with cisplatin in a weekly-based regimen as neoadjuvant chemotherapy is effective and tolerable for locally advanced breast cancer.

In patients with some sub-type advanced breast cancer, neo-adjuvant chemotherapy combined with endocrine therapy may improve the pathological remission rate.

Premenopausal patients with triple negative breast caner and hormonal receptor positve breast cancer patients will be randominzed to have neoadjuvant chemotherapy combined with endocrine therapy or not.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Breast Cancer; Invasive Ductal Breast Cancer; Tubular Breast Cancer; Mucinous Breast Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Letrozole; Drug: Paclitaxel; Drug: Gonadotropin-releasing hormone agonist

Detailed Description

In this trial, patients with ER and or PR positive breast cancer will be separately randomized to have chemotherapy or chemotherapy combined with endocrine therapy according to their menstrual status. Letrozole for the postmenopausal women and ovarian function suppression for the premenopausal women. Patients with triple negative breast cancer will be randomized to have neoadjuvant chemotherapy combined with ovarian function suppression if she is premenopausal. Postermenopausal patients with triple negative breast caner will only have neoadjuvant chemotherapy.

Patients with Her2 overexpression can obtain anti-Her2 target therapy. This study has been amended to a 1:2 ratio to control and neoadjuvant chemotherapy combination of endocrine therapy.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Department of Thyroid and Breast Gland Surgery,Shenzhen Longgang Central Hospital
  • Hebei
    • Handan, Hebei, China, 056001
      • Handan Central Hospital
  • Hunan
    • Hengyang, Hunan, China, 421001
      • The First Affiliated Hospital of University of South China
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China
      • Department of Thyroid and Breast Surgery, The Affiliated Hospital of Inner Mongolia Medical Collage
  • Jiangsu
    • Kunshan, Jiangsu, China, 215300
      • The second people's hospital of Kunshan city
  • Ningxia
    • Yinchuan, Ningxia, China
      • Department of Medical Oncology, General Hospital of Ningxia Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan hospital
    • Shanghai, Shanghai, China, 200127
      • Shanghai Jiaotong University School of Medicine, Renji Hospital
    • Shanghai, Shanghai, China, 200437
      • Yueyang hospital of integrated traditional Chinese and Western medine
    • Shanghai, Shanghai, China, 201103
      • Armed Police Corps Hospital of Shanghai
    • Shanghai, Shanghai, China
      • Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University
  • Zhejiang
    • Zhoushan, Zhejiang, China, 316021
      • Zhoushan Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Women aged ≥18years and ≤70 years;
2. At least on measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Histologically confirmed invasive breast cancer, tumor size ≥2 cm, T2-4 N0-3M0;
3. ER/PR/HER-2 and Ki-67 status detected on core biopsy. ER and/or PR positive was defined as >1% stained cells.HER2-positive is defined as immuno-histochemistry (IHC) 3+ or the ratio of HER2 gene signals to chromosome 17 signals >2.0 or HER2 gene copy >6.0.
4. No prior systemic or loco-regional treatment of breast cancer;
5. Adequate bone marrow function:WBC≥4.0×109/L, Absolute neutrophil count（ANC）≥1.5×109/L, Platelets（PLT）≥100×109/L, Hemoglobin（Hb）≥90g/L;aspartate aminotransferase(AST),Alanine aminotransferase (ALT)≤1.5 upper normal limit (UNL), creatinine≤1.5 UNL, bilirubin≤1.5UNL;
6. No obvious main organs dysfunction.

Exclusion Criteria:

1. Unwilling or unable to use an acceptable method of contraception in 8 weeks (including 8 weeks) after final dose of test drug;
2. Patient is pregnant or breast feeding;
3. Inflammatory breast cancer and metastatic breast cancer;
4. Any evidence of sense or motor nerve disorders;
5. Patients with medical conditions taht indicate intolerant to neoadjuvant therapy, including uncontrolled cardiovascular disease, severe infection;
6. Any concurrent malignancy other than breast cancer;
7. Know severe hypersensitivity to any drugs in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemotherapy only; Paclitaxel injection 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle；Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle； for 4 cycles	Drug: Cisplatin; Drug: Paclitaxel; Other Names: Taxol
Experimental: GnRHa; Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Gonadotropin-releasing hormone agonist （GnRHa）11.25 mg every 3 months or 3.6mg every month subcutaneously	Drug: Cisplatin; Drug: Paclitaxel; Other Names: Taxol; Drug: Gonadotropin-releasing hormone agonist; Goserelin 3.6 mg q28d or Leuprolide 11.25 mg q3m
Experimental: letrozole; Paclitaxel 80mg/m2,given on days1,8,15 and 22 of a 28-day cycle; Cisplatin 25mg/m2, given on days 1,8,and 15 of a 28-day cycle; for 4 cycles Letrozole 2.5mg/day	Drug: Cisplatin; Drug: Letrozole; Drug: Paclitaxel; Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete remission rate	Pathological complete remission is defined as no invasive cancer in breast and axillary nodes.	after 4 months preoperative treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and imaging response	To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment	4 months during treatment
regional recurrence free survival (RRFS)	RRFS is defined as the time period between registration and first event	5 years
local recurrence free survival (LRFS)	LRFS is defined as the time period between registration and first event	5 years
overall survival (OS)	OS is defined as the time period between registration and first event	5 years
Number of Participants With Drug Related Treatment Adverse Events	Adverse events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state.	4 months during neoadjuvant therapy
distant-disease- free survival (DDFS)	DDFS is defined as the time period between registration and first event	5 years
rate of tumor remission （RTR）	RTR is defined as the proportion of tumor remission per unit time	after 2 cycles and 4 cycles during neoadjuvant therapy
serum markers	Changes in the angiogenic serum markers(mirRNA, lncRNA, cirRNA), measured at diagnosis and surgery	Pre-treatment and/or surgical
molecular markers	Pre-treatment and surgical expression of molecular markers （LHRHa receptor, EGFR，PD-L1)	Pre-treatment and/or surgical
disease free survival (DFS)	DFS is defined as the time in months from randomization until first occurrence of locoregional recurrence, distant metastasis, contralateral breast cancer, second primary tumor, or death from any cause.	5 years

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Jinsong Lu, Renji Hospital

Publications and helpful links

General Publications

• Bayarmaa B, Wu Z, Peng J, Wang Y, Xu S, Yan T, Yin W, Lu J, Zhou L. Association of LncRNA MEG3 polymorphisms with efficacy of neoadjuvant chemotherapy in breast cancer. BMC Cancer. 2019 Sep 5;19(1):877. doi: 10.1186/s12885-019-6077-3.
• Wu Z, Zhang L, Xu S, Lin Y, Yin W, Lu J, Sha R, Sheng X, Zhou L, Lu J. Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy. Cancer Cell Int. 2019 Mar 29;19:78. doi: 10.1186/s12935-019-0793-2. eCollection 2019.
• Sun L, Yin W, Wu Z, Wang Y, Lu J. The Predictive Value of Pre-therapeutic Serum Gamma-glutamyl transferase in Efficacy and Adverse Reactions to Neoadjuvant Chemotherapy among Breast Cancer Patients. J Breast Cancer. 2020 Oct;23(5):509-520. doi: 10.4048/jbc.2020.23.e59.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): January 1, 2019
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: July 14, 2014
• First Submitted That Met QC Criteria: August 20, 2014
• First Posted (Estimated): August 21, 2014

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma, Ductal; Breast Neoplasms; Inflammatory Breast Neoplasms; Carcinoma, Ductal, Breast; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Phytogenic; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Paclitaxel; Letrozole; Hormones
• Other Study ID Numbers: RenJiH-BC-002