Efficacy and Safety Study of Trastuzumab, Paclitaxel and Carboplatin on HER2+ Preoperative Breast Cancer (PCH)

A Randomized Study to Investigate the Efficacy and Safety of qw or q3w Trastuzumab, Paclitaxel and Carboplatin in Patients With IIB-IIIB HER2 Positive Breast Cancer

To compare the efficacy in terms of the pathological complete response rate (pCR) to preoperative administration of qw or q3w Paclitaxel, Carboplatin and Trastuzumab (PCH)

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab QW, Trastuzumab Q3W

Detailed Description

Currently Herceptin has moved to Neoadjuvant treatment combined with chemotherapy. Paclitaxel and Carboplatin are two of the best partners with high pCR. The significant efficacy and good safety profile of Herceptin® combination with taxane as adjuvant treatment on EBC are accepted; 1 year of Herceptin as adjuvant treatment is one standard therapy. This study is one small Phase II trial to explore the efficacy and safety of QW and Q3W of PCH as Neoadjuvant treatment, we only plan 60 pts and the trend of the two curves is anticipated

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhimin Shao, Post-Doctor; Phone Number: 8888 86 21 64175590; Email: zhimingshao@yahoo.com
• Study Contact Backup: Name: Canmin Chen, Bachelor; Phone Number: 8603 86 21 64175590; Email: cmchen@medmail.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Cancer Hospital Affiliated to Fudan University
      • Contact: Zhimin Shao, Post-Doctor; Phone Number: 8888 86 21 64175590; Email: zhimingshao@yahoo.com

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:

1. Women aged equals to or more than 18 years and no more than 70 years with life expectancy more than 12 months
2. Histologically confirmed invasive breast cancer (excluding inflammatory breast cancer) by core needle biopsy, T2N1 or local advanced breast cancer, with no evidence of metastasis
3. HER2 positive confirmed by FISH/CISH+ or IHC 3+
4. With no history of cancer other than in situ uterine cervix cancer or skin basal cell carcinoma
5. Adequate hematopoietic function: Neutrophil larger than 1.5*109/L; Hb larger than 100g/L; PLT larger than 100*109/L

6. Adequate hepatic and renal function

   • serum AST less than 60U/L
   • Total bilirubin less than 1.5 ULN
   • serum creatinine less than 110umol/L
   • BUN less than 7.1mmol/L
7. LVEF 55% by MUGA scan or echocardiography
8. Adequate coagulation function
9. ECOG PS 0-1
10. Willing to take biopsy before surgery and during chemotherapy and willing to take pre-operative chemotherapy and related treatment
11. Women of child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to take an adequate contraceptive measure
12. Signed written informed consent; Able to comply with the protocol

Exclusion Criteria:

1. Prior systemic or loco-regional treatment of breast cancer, including chemotherapy
2. Metastatic breast cancer
3. Patients with medical conditions that renders them intolerant to neoadjuvant therapy and related treatment, including uncontrolled pulmonary disease, Diabetes Mellitus, severe infection, active peptic ulcer, Coagulation disorder, connective tissue disease or myelo-suppressive disease
4. History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (Systolic BP more than 180mmHg or Diastolic BP more than 100mmHg）
5. grade 1 peripheral neuropathy from any cause
6. Patient is pregnant or nursing
7. Not willing to take pre-operative biopsy or neo-adjuvant therapy
8. Patients with psychiatric disorder or other disease leading to incompliance to the therapy
9. Known hypersensitivity to any ingredient of the regimen
10. Treatment with any investigational drug within 30 days before the beginning of treatment with study drug

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Trastuzumab QW; Arm A: Trastuzumab 2mg/kg, d1; qw (loading dose 4mg/kg wk1) Paclitaxel 80mg/m2,. d1; qw Carboplatin AUC 2 d1, qw	Drug: Trastuzumab QW, Trastuzumab Q3W; two arms using Trastuzumab QW vs Q3W; Other Names: Herceptin
Active Comparator: Trastuzumab Q3W; Arm B: Trastuzumab 6mg/kg, d1(loading dose 8mg/kg wk1) Paclitaxel 175mg/m2,. d1, q3w; Carboplatin AUC 6 ,. d1,q3w	Drug: Trastuzumab QW, Trastuzumab Q3W; two arms using Trastuzumab QW vs Q3W; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint is efficacy. To compare the efficacy in terms of the pathological complete response rate (pCR) to preoperative administration of qw or q3w Paclitaxel, Carboplatin and Trastuzumab (PCH).	Primary Endpoint is efficacy. To compare the efficacy in terms of the pathological complete response rate (pCR) to preoperative administration of qw or q3w Paclitaxel, Carboplatin and Trastuzumab (PCH). The primary efficacy variable is the rate of pathological complete response (pCR). Time to recurrence will be measured as the time from when the patient was randomized to the time the patient is first recorded as having disease recurrence or the date of death if the patient dies due to causes other than disease recurrence.	3 years from last patient randomized

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Zhimin Shao, Post-Doctor, Cancer Hospital Affiliated to Fudan University

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: July 21, 2010
• First Submitted That Met QC Criteria: July 26, 2010
• First Posted (Estimate): July 27, 2010

Study Record Updates

• Last Update Posted (Estimate): July 27, 2010
• Last Update Submitted That Met QC Criteria: July 26, 2010
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: IIB-IIIB Breast Cancer; Her2 positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: ML22700