Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer (EPHOS-B)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Institute of Cancer Research, United Kingdom
Sponsor:
Collaborators:
University of Manchester
University Hospital of South Manchester NHS Foundation Trust
Cancer Research UK
GlaxoSmithKline
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier:
NCT01104571
First received: April 13, 2010
Last updated: May 27, 2014
Last verified: May 2014
  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.

Update June 2013:

Since the initial development of EPHOS-B in 2007 more evidence in relation to safety and efficacy of anti-HER2 therapies are now available, and in particular, a growing body of evidence that combinations of two anti-HER2 therapies are more effective than monotherapies. Therefore this study has been amended (PART 2) to a 1:1:2 ratio to control, perioperative trastuzumab or the combination of lapatinib and trastuzumab.

PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works compared with lapatinib ditosylate (and in since June 2013 - Part 2 - compared with a combination of lapatinib and trastuzumab) 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
Intervention Model: Parallel Assignment
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:


Further study details as provided by Institute of Cancer Research, United Kingdom:

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) [ Time Frame: 10-13 days ] [ 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) [ Time Frame: 10-13 days ] [ Designated as safety issue: No ]
  • Relapse-free survival (clinical phase) [ Time Frame: TBC ] [ 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) [ Time Frame: TBC ] [ 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) [ Time Frame: TBC ] [ Designated as safety issue: No ]
  • Time to local recurrence (clinical phase) [ Time Frame: TBC ] [ Designated as safety issue: No ]
  • Time to distant recurrence (clinical phase) [ Time Frame: TBC ] [ Designated as safety issue: No ]
  • Overall survival (clinical phase) [ Time Frame: TBC ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: April 2010
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Part 1: Control
No peri-operative therapy given
Other: laboratory biomarker analysis Procedure: therapeutic conventional surgery
therapeutic conventional surgery
Experimental: Part 1: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
Biological: trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery
Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: neoadjuvant therapy
Experimental: Part 1: lapatinib
Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery
Drug: lapatinib ditosylate

Part 1: Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery.

Part 2: Lapatinib 1000mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery.

Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: neoadjuvant therapy
Part 2: Control
No peri-operative therapy
Other: laboratory biomarker analysis Procedure: therapeutic conventional surgery
therapeutic conventional surgery
Experimental: Part 2: Trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery.
Biological: trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery
Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: neoadjuvant therapy
Experimental: Part 2: lapatinib- trastuzumab combination
Lapatinib 1000mg/day p.o. continuously for 28 days, in combination with trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery. Both drugs should start 11 days (+2 or -1 day) before the scheduled surgery.
Biological: trastuzumab
Trastuzumab 6mg/kg iv given on days 1 & 8 pre-surgery & one dose of 2mg/kg iv between days 15-19 post surgery
Drug: lapatinib ditosylate

Part 1: Lapatinib 1500mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery.

Part 2: Lapatinib 1000mg/day p.o. continuously for 28 days. Should start 11 days (+2 or -1 day) before the scheduled surgery.

Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: neoadjuvant therapy

  Show Detailed Description

  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 3 weeks
    • Estrogen receptor-negative patients may enter the trial whether or not they have taken HRT within the past 3 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 1 day 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104571

Contacts
Contact: Mark Webster-Smith (+44)2087224315 ephos-b-icrctsu@icr.ac.uk

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
University of Manchester
University Hospital of South Manchester NHS Foundation Trust
Cancer Research UK
GlaxoSmithKline
Investigators
Principal Investigator: Nigel Bundred Wythenshawe Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Institute of Cancer Research, United Kingdom
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: May 27, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Institute of Cancer Research, United Kingdom:
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
Lapatinib
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014