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

Sponsor

RenJi Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02221999

Collaborator

(none)

250

Enrollment

Locations

Arms

105

Anticipated Duration (Months)

31.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tubular Breast Cancer Mucinous Breast Cancer Invasive Ductal Breast Cancer Inflammatory Breast Cancer	Drug: Paclitaxel Drug: Cisplatin Drug: Gonadotropin-releasing hormone agonist Drug: Letrozole	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2014

Actual Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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: Paclitaxel Other Names: Taxol Drug: Cisplatin
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: Paclitaxel Other Names: Taxol Drug: Cisplatin 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: Paclitaxel Other Names: Taxol Drug: Cisplatin Drug: Letrozole

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: Paclitaxel

Other Names:

Taxol

Drug: Cisplatin

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: Paclitaxel

Other Names:

Taxol

Drug: Cisplatin

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: Paclitaxel

Other Names:

Taxol

Drug: Cisplatin

Drug: Letrozole

Outcome Measures

Primary Outcome Measures

pathological complete remission rate [after 4 months preoperative treatment]
Pathological complete remission is defined as no invasive cancer in breast and axillary nodes.

Secondary Outcome Measures

Number of Participants With Drug Related Treatment Adverse Events [4 months during neoadjuvant therapy]
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.
Clinical and imaging response [4 months during treatment]
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
regional recurrence free survival (RRFS) [5 years]
RRFS is defined as the time period between registration and first event
local recurrence free survival (LRFS) [5 years]
LRFS is defined as the time period between registration and first event
overall survival (OS) [5 years]
OS is defined as the time period between registration and first event
distant-disease- free survival (DDFS) [5 years]
DDFS is defined as the time period between registration and first event
rate of tumor remission （RTR） [after 2 cycles and 4 cycles during neoadjuvant therapy]
RTR is defined as the proportion of tumor remission per unit time
serum markers [Pre-treatment and/or surgical]
Changes in the angiogenic serum markers(mirRNA, lncRNA, cirRNA), measured at diagnosis and surgery
molecular markers [Pre-treatment and/or surgical]
Pre-treatment and surgical expression of molecular markers （LHRHa receptor, EGFR，PD-L1)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women aged ≥18years and ≤70 years;
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;
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.

No prior systemic or loco-regional treatment of breast cancer;
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;
No obvious main organs dysfunction.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HanDan Central Hospital	Handan	Hebei	China	056001
2	The First Affiliated Hospital of University of South China	Hengyang	Hunan	China	421001
3	The second people's hospital of Kunshan city	Kunshan	Jiangsu	China	215300
4	Zhongshan Hospital	Shanghai	Shanghai	China	200032
5	Shanghai Jiaotong University School of Medicine, Renji Hospital	Shanghai	Shanghai	China	200127
6	Yueyang hospital of integrated traditional Chinese and Western medine	Shanghai	Shanghai	China	200437
7	Armed Police Corps Hospital of Shanghai	Shanghai	Shanghai	China	201103
8	Zhoushan hospital	Zhoushan	Zhejiang	China	316021