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Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer

This study is currently recruiting participants.
Verified July 2011 by National Cancer Institute (NCI)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01104571
First received: April 13, 2010
Last updated: July 29, 2011
Last verified: July 2011
History of Changes
  Purpose

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trastuzumab or lapatinib ditosylate is more effective in treating women with early breast cancer.

PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works compared with lapatinib ditosylate in treating women with early breast cancer.


Condition Intervention Phase
Breast Cancer
 Biological: trastuzumab
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Perioperative AntiHER-2 Therapy on Early Breast Cancer Study - Biological Phase (EPHOS-B)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Increase in apoptosis, by change in the tumor (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery (biological phase) [ Designated as safety issue: No ]
  • Fall in proliferation between diagnosis and surgery by change in proliferation measured by Ki67 immunohistochemical assessment (%) at diagnosis and at surgery (biological phase) [ Designated as safety issue: No ]
  • Relapse-free survival (clinical phase) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in the angiogenic serum markers VEGF-A, VEGF R1, and CD105, measured at diagnosis, surgery (plus also tumor CD31) and 28-30 days post surgery (biological phase) [ Designated as safety issue: No ]
  • Pre-treatment and/or surgical expression of molecular markers (EGFR, Her-3, IGF1R, c-myc, AKT, p-ERK, pS6 inase, activated src, or truncated p95HER-2 expression) [ Designated as safety issue: No ]
  • Time to local recurrence (clinical phase) [ Designated as safety issue: No ]
  • Time to distant recurrence (clinical phase) [ Designated as safety issue: No ]
  • Overall survival (clinical phase) [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: April 2010
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine whether pre-operative treatment of HER-2 positive breast cancer patients with anti-HER2 therapy consisting of trastuzumab (Herceptin®) vs lapatinib ditosylate inhibits proliferation or increases apoptosis.
  • To compare trastuzumab (Herceptin®) and lapatinib ditosylate effects on inhibition of proliferation or increase of apoptosis.

Secondary

  • To determine whether pre-operative anti-HER2 treatment reduces serum angiogenic factors.

OUTLINE: This is a multicenter study. Patients are stratified according to center. Patients are randomized to 1 of 3 treatment arms.

  • Arm I (control): Patients receive no neoadjuvant or adjuvant therapy. Approximately 14 days after randomization, patients undergo either breast-conservation surgery or mastectomy.
  • Arm II (trastuzumab [Herceptin®]): Patients receive neoadjuvant trastuzumab IV over 90 minutes on days 1 and 8. Approximately 11 days after beginning of neoadjuvant therapy, patients undergo either breast-conservation surgery or mastectomy, and receive adjuvant trastuzumab on day 15.
  • Arm III (lapatinib ditosylate): Patients receive neoadjuvant oral lapatinib ditosylate once daily on days 1-11. Within 24 hours after completion of neoadjuvant therapy, patients undergo either breast-conservation surgery or mastectomy, and receive adjuvant lapatinib ditosylate once daily on days 12-28.

Patients also receive standard adjuvant systemic therapy, including endocrine therapy (for hormone-sensitive disease) and/or chemotherapy and radiotherapy.

All patients undergo blood and tissue sample collection periodically for biomarker research studies comprising biomarkers of proliferation, apoptosis, and angiogenesis.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 10 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed (by core biopsy) invasive breast cancer

    • Newly diagnosed disease
    • Resectable disease
  • HER2-positive disease, defined as 3+ measured by IHC or gene amplification by fluorescent in situ hybridization (FISH)
  • No evidence of metastatic disease (T4 category) or suspicion of distant metastases
  • No inflammatory breast cancer
  • Planned surgery within 1 month of diagnosis, and willing to undergo adjuvant chemotherapy and trastuzumab post-surgery
  • Must consent to donation of tissue and blood samples

  • Hormone receptor status known

    • Estrogen receptor-positive patients on hormone replacement therapy (HRT) must either continue HRT or must not have taken HRT within the past 4 weeks
    • Estrogen receptor-negative patients may enter the trial whether or not they have taken HRT within the past 4 weeks

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Serum creatinine < 2 times upper limit of normal (ULN) OR creatinine clearance > 30 mg/dL
  • Bilirubin < 2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective non-hormonal contraception
  • LVEF ≥ 55% by echocardiography or MUGA
  • No clinically significant cardiac abnormalities or uncontrolled hypertension
  • No prior myocardial infarction, heart failure, or significant angina
  • No prior cancer at any other site that has been treated within the past 6 months (except basal cell carcinoma or cervical carcinoma in situ)
  • No current active hepatic or biliary disease (except Gilbert syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per investigator assessment)
  • No impaired gastrointestinal function that would sufficiently reduce lapatinib ditosylate absorption
  • No known immediate or delayed hypersensitivity or reaction to drugs chemically related to trastuzumab or lapatinib ditosylate
  • No altered mental state that would preclude obtaining written informed consent

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior trastuzumab (Herceptin®) therapy within the past 3 months
  • No prior local cancer treatment (e.g., radiotherapy)
  • No other concurrent investigational agent or anticancer therapy
  • No use of herbal (alternative) therapies within 2 weeks of study entry (vitamin and/or mineral supplements allowed)
  • No regular use of systemic steroids or other agents that could influence study endpoints (inhaled steroids allowed)
  • No grapefruit and grapefruit juice for the duration of the study
  • At least 14 days since prior and no concurrent CYP3A4 inducers
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors
  • At least 6 months since prior and no concurrent amiodarone
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01104571

Locations
United Kingdom
Wythenshawe Hospital Recruiting
Manchester, England, United Kingdom, M23 9LJ
Contact: Contact Person     44-208-722-4154     Nigel.j.bundred@manchester.ac.uk    
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Investigators
Principal Investigator: Nigel Bundred Wythenshawe Hospital
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier: NCT01104571     History of Changes
Other Study ID Numbers: CDR0000669882, ICR-CTSU-2008-10017, UM-EPHOS-B, CRUK-08-002, MREC-09-H1208-52, ISRCTN-15004993, EUDRACT-2008-005466-30, EU-21029, GSK-ICR-CTSU-2008-10017
Study First Received: April 13, 2010
Last Updated: July 29, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
HER2-positive breast cancer
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
 stage IIIA breast cancer
estrogen receptor-negative breast cancer
estrogen receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Lapatinib
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 17, 2013