Efficacy and Safety Study of Trastuzumab and Paclitaxel Based Regimens to Treat HER2-positive Breast Cancer

HER-2 Positive Breast Cancer Clinical Trial

Official title:

Multicenter, Randomized, Open-label Phase II Study to Compare the Efficacy and Safety of Trastuzumab and Paclitaxel Based Regimen Plus Carboplatin or Epirubicin as Neoadjuvant Therapy in HER2-positive Breast Cancer Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01428414
• Other study ID #: ML27770
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 28, 2011
• Last updated: August 21, 2012
• Start date: August 2011
• Est. completion date: February 2015

Study information

• Verified date: August 2012
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of the investigators study is to compare the efficacy and safety of combining trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy in Chinese HER2-positive breast cancer patients. 100 patients from multicenter would be randomly assigned into two treatment arms and receive neoadjuvant chemotherapy followed by operation and adjuvant treatment. The main end point of this study would be the efficacy and safety of the two treatment arms, and the trend of the two curves is anticipated.

Description:

With the increased awareness and development of the diagnosis of breast cancer, more and more breast cancer is diagnosed at early. Amplification or overexpression, or both, of human epidermal growth factor receptor-2 (HER2, also known as ERBB2), a transmembrane receptor tyrosine kinase, is present in around 22% of early breast cancers, 35% of locally advanced and metastatic tumors, and 40% of inflammatory breast cancers, and is associated with aggressive disease and poor prognosis. The significant efficacy and good safety profile of Trastuzumab targeting HER 2 combination with chemotherapy as adjuvant treatment on EBC are accepted. Currently Trastuzumab has moved to Neoadjuvant treatment combined with chemotherapy based on many publications, among them pCR is accepted as primary endpoint to evaluate the efficacy of neoadjuvant therapy.

In the investigators study, Trastuzumab was concomitantly administered with different chemotherapies after randomization to determine the effect of this approach on the pathologic CR rates. 100 patients from multicenter would be randomly assigned into two treatment arms and receive neoadjuvant chemotherapy followed by operation and adjuvant treatment. Pathological complete response rate (pCR), disease free survival (DFS), response rates (RR), percentage of conserving breast surgery and adverse events including Serious AEs and non-serious AEs would be compared. The follow up time for each patients would be 3 years at most.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: February 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

1. Female patients, presenting for the first time with invasive breast cancer, who have not received any previous treatment for an invasive malignancy

2. Aged =18 years and < 70 years with life expectancy > 12 months

3. Histologically confirmed invasive breast cancer (excluding inflammatory breast cancer) by core needle biopsy, staged II-III according to TNM Classification System, with no evidence of metastasis and tumor size =3 cm

4. HER2 positive confirmed by IHC 2+ and FISH positivity or IHC 3+

5. At least one measurable lesion according to RECIST criteria 1.1

6. Patients with a left ventricular ejection fraction(LVEF)=55% by MUGA scan or echocardiography

7. ECOG PS 0-1

8. Willing to take biopsy before surgery and during chemotherapy and willing to take pre-operative chemotherapy and related treatment

9. Signed written informed consent; Able to comply with the protocol

Exclusion Criteria:

1. Patient is pregnant or lactating.

2. 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

3. Previous treatment with chemotherapy or hormonal therapy or any prior therapy with an anti-HER2 therapy for any malignancy.

4. History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction

5. Other invasive malignancy (including second primary breast cancer) which could affect compliance with the protocol or interpretation of results. Patients who have been curatively treated and free of malignant disease for greater than 5 years are generally eligible

6. Inadequate bone marrow, hepatic and renal functions as evidenced by the following:

• Neutrophil count of <1500/uL,

• Platelet count of <100,000/uL.

• Haemoglobin <10 g/dL.

• Serum total bilirubin > 1.5*ULN (upper limit of normal),

• ALT or AST > 2.5*ULN,

• Alkaline phosphatase > 2.5*ULN,

• Serum creatinine > 1.5*ULN.

7. Other serious illness or medical condition including:

• Congestive heart failure (NYHA class II, III, IV) or history of documented congestive heart failure, unstable angina pectoris, myocardial infarction in the last 6 months, clinically significant valvular heart disease, or high-risk uncontrolled arrhythmias.

• Patients with dyspnoea at rest due to malignant or other disease (e.g. pulmonary metastases with lymphangitis) or who require supportive oxygen therapy.

• Active serious uncontrolled infections.

• Poorly controlled diabetes mellitus.

8. Not willing to take pre-operative biopsy or neo-adjuvant therapy

9. Patients with psychiatric disorder or other disease leading to incompliance to the therapy

10. Known hypersensitivity to any ingredient of the regimen

11. Treatment with any investigational drug within 30 days before the beginning of treatment with study drug.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• HER-2 Positive Breast Cancer

Intervention

Drug:
• Trastuzumab
2 mg/kg, iv, d1,8,15(loading dose 4mg/kg wk1), qw
• Paclitaxel
75mg/m2, iv d1, 8,15. qw; 4-6 cycles
• Epirubicin
75mg/m2, iv d1, q3w, 4-6 cycles
• Carboplatin
AUC 2, qw, iv d1, 8,15. 4-6 cycles

Locations

Country	Name	City	State
China	Breast cancer institute of Fudan University Cancer Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Zhimin Shao	Roche Pharma AG

Country where clinical trial is conducted

China, 

References & Publications (6)

Chang HR. Trastuzumab-based neoadjuvant therapy in patients with HER2-positive breast cancer. Cancer. 2010 Jun 15;116(12):2856-67. doi: 10.1002/cncr.25120. Review. — View Citation

Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. doi: 10.1016/S0140-6736(09)61964-4. — View Citation

Han S, Kim J, Lee J, Chang E, Gwak G, Cho H, Yang KH, Park S, Park K. Comparison of 6 cycles versus 4 cycles of neoadjuvant epirubicin plus docetaxel chemotherapy in stages II and III breast cancer. Eur J Surg Oncol. 2009 Jun;35(6):583-7. doi: 10.1016/j.ejso.2009.01.002. Epub 2009 Feb 5. — View Citation

Nisticò C, Bria E, Cuppone F, Fornier M, Sperduti I, Carpino A, Pace A, Cognetti F, Terzoli E. Weekly epirubicin and paclitaxel with granulocyte colony-stimulating factor support in previously untreated metastatic breast cancer patients: a phase II study. Anticancer Drugs. 2007 Jul;18(6):687-92. — View Citation

Piccart-Gebhart MJ, Burzykowski T, Buyse M, Sledge G, Carmichael J, Lück HJ, Mackey JR, Nabholtz JM, Paridaens R, Biganzoli L, Jassem J, Bontenbal M, Bonneterre J, Chan S, Basaran GA, Therasse P. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer. J Clin Oncol. 2008 Apr 20;26(12):1980-6. doi: 10.1200/JCO.2007.10.8399. — View Citation

Sikov WM, Dizon DS, Strenger R, Legare RD, Theall KP, Graves TA, Gass JS, Kennedy TA, Fenton MA. Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. J Clin Oncol. 2009 Oct 1;27(28):4693-700. doi: 10.1200/JCO.2008.21.4163. Epub 2009 Aug 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pathologic complete response rate	Percentage of complete pathological response, e.g. no microscopic evidence of residual invasive tumor cells in any resected specimens of the breast and/or axillary nodes.	3 years	No
Secondary	Disease free survival	Percentage of recurrence-free survival using Kaplan-Meier method, including subgroup analysis of DFS who complete 1-year trastuzumab treatment	3 years at most	No
Secondary	Overall response rate	Percentage of clinical objective response using the RECIST scale	3 years	No
Secondary	Percentage of conserving breast surgery	Percentage of conserving breast surgery	3 years	No
Secondary	Safety	Incidence and severity of adverse events using the NCI-CTC scale 4.0	3 years	Yes