HER-2 Positive Breast CancerPhase 2NCT01428414
Efficacy and Safety Study of Trastuzumab and Paclitaxel Based Regimens to Treat HER2-positive Breast Cancer
A Phase 2 study testing Trastuzumab, Paclitaxel and Epirubicin in people with HER-2 Positive Breast Cancer, run by Zhimin Shao at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 69 years, women only
- Conditions the study is for
- HER-2 Positive Breast Cancer
- What is being tested?
- Trastuzumab, Paclitaxel and Epirubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Aug 2011to Feb 2015
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients, presenting for the first time with invasive breast cancer, who have not received any previous treatment for an invasive malignancy
- Aged ≥18 years and < 70 years with life expectancy > 12 months
- 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
- HER2 positive confirmed by IHC 2+ and FISH positivity or IHC 3+
- At least one measurable lesion according to RECIST criteria 1.1
- Patients with a left ventricular ejection fraction(LVEF)≥55% by MUGA scan or echocardiography
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- ECOG PS 0-1
- Willing to take biopsy before surgery and during chemotherapy and willing to take pre-operative chemotherapy and related treatment
- Signed written informed consent; Able to comply with the protocol
Who cannot join
- Patient is pregnant or lactating.
- 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
- Previous treatment with chemotherapy or hormonal therapy or any prior therapy with an anti-HER2 therapy for any malignancy.
- History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction
- 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
- Inadequate bone marrow, hepatic and renal functions as evidenced by the following:
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- 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.
- 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.
- Not willing to take pre-operative biopsy or neo-adjuvant therapy
- Patients with psychiatric disorder or other disease leading to incompliance to the therapy
- Known hypersensitivity to any ingredient of the regimen
- Treatment with any investigational drug within 30 days before the beginning of treatment with study drug.
Trial locations and contacts
1 site in 1 country.
China1 site
Breast cancer institute of Fudan University Cancer Hospital
Shanghai, Shanghai Municipality, 200032
About this study
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
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.
Read the detailed 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.
- Conditions
- HER-2 Positive Breast Cancer
- Being tested
- Trastuzumab, Paclitaxel, Epirubicin, Carboplatin
- Keywords
- HER2, Breast cancer, neoadjuvant chemotherapy, efficacy, safety
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
2 mg/kg, iv, d1,8,15(loading dose 4mg/kg wk1), qw
PaclitaxelDrug
Also called Taxol
75mg/m2, iv d1, 8,15. qw; 4-6 cycles
EpirubicinDrug
Also called Epirubicin Hydrochloride for Injection
75mg/m2, iv d1, q3w, 4-6 cycles
CarboplatinDrug
Also called CARBOPLATIN FOR INJECTION
AUC 2, qw, iv d1, 8,15. 4-6 cycles
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab+ Carboplatin+Paclitaxel | Active comparator | Neoadjuvant treatment regimen:Trastuzumab,Carboplatin,Paclitaxel Receives: Drug: Trastuzumab; Drug: Paclitaxel; Drug: Carboplatin |
| Trastuzumab+Epirubicin+Paclitaxel | Active comparator | Neoadjuvant treatment regimen:Trastuzumab,Epirubicin,Paclitaxel Receives: Drug: Trastuzumab; Drug: Paclitaxel; Drug: Epirubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (4)
Disease free survival
Percentage of recurrence-free survival using Kaplan-Meier method, including subgroup analysis of DFS who complete 1-year trastuzumab treatment
Measured: 3 years at most
Overall response rate
Percentage of clinical objective response using the RECIST scale
Measured: 3 years
Percentage of conserving breast surgery
Percentage of conserving breast surgery
Measured: 3 years
Safety
Incidence and severity of adverse events using the NCI-CTC scale 4.0
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2011 (estimated)
- Study startAug 2011
- Primary completionAug 2014 (estimated)
- Study completionFeb 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HER-2 Positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhimin Shao
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor-investigator, Zhimin Shao, Fudan University
- Investigators
- Zhi-Ming Shao, MD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01428414
- Sponsor's protocol ID
- ML27770
- Status last verified
- Aug 2012
- First submitted
- 28 Aug 2011
- Last updated
- 23 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19720916Chang 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.
PubMed 20564392Piccart-Gebhart MJ, Burzykowski T, Buyse M, Sledge G, Carmichael J, Luck 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.
PubMed 18421049Nistico 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. doi: 10.1097/CAD.0b013e328035f863.
PubMed 17762397Gianni 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.
PubMed 20113825Han 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.
PubMed 19195817