Trastuzumab or Lapatinib Ditosylate in Treating Women With Early Breast Cancer

NCT01104571 | Unknown Phase 3 DMC

• 8 other identifiers: CDR0000669882ICR-CTSU-2008-10017UM-EPHOS-BCRUK-08-002MREC-09-H1208-52ISRCTN-150049932008-005466-30EU-21029
• Study Type: interventional
• Target: 257
• Locations: 1 country
• Sites: 1

Brief Summary

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 - compared with a combination of lapatinib and trastuzumab) in treating women with early breast cancer.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Increase in apoptosis, by change in the tumor (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery (biological phase)

  10-13 days

• Fall in proliferation between diagnosis and surgery by change in proliferation measured by Ki67 immunohistochemical assessment (%) at diagnosis and at surgery (biological phase)

  10-13 days

• Relapse-free survival (clinical phase)

  TBC

Secondary Outcomes (5)

• 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)

  TBC

• 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)

  TBC

• Time to local recurrence (clinical phase)

  TBC

• Time to distant recurrence (clinical phase)

  TBC

• Overall survival (clinical phase)

  TBC

Study Arms (6)

Part 1: Control

OTHER

No peri-operative therapy given

Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery

Part 1: Trastuzumab

EXPERIMENTAL

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

Part 1: lapatinib

EXPERIMENTAL

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

Drug: lapatinib ditosylate; Other: laboratory biomarker analysis; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy

Part 2: Control

OTHER

No peri-operative therapy

Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery

Part 2: Trastuzumab

EXPERIMENTAL

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

Part 2: lapatinib-trastuzumab combination

EXPERIMENTAL

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; Drug: lapatinib ditosylate; Other: laboratory biomarker analysis; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy

Interventions

trastuzumab BIOLOGICAL

Trastuzumab 6mg/kg iv given on days 1 \& 8 pre-surgery \& one dose of 2mg/kg iv between days 15-19 post surgery

Part 1: Trastuzumab; Part 2: Trastuzumab; Part 2: lapatinib-trastuzumab combination

lapatinib ditosylate DRUG

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.

Part 1: lapatinib; Part 2: lapatinib-trastuzumab combination

laboratory biomarker analysis OTHER

Part 1: Control; Part 1: Trastuzumab; Part 1: lapatinib; Part 2: Control; Part 2: Trastuzumab; Part 2: lapatinib-trastuzumab combination

adjuvant therapy PROCEDURE

Part 1: Trastuzumab; Part 1: lapatinib; Part 2: Trastuzumab; Part 2: lapatinib-trastuzumab combination

neoadjuvant therapy PROCEDURE

Part 1: Trastuzumab; Part 1: lapatinib; Part 2: Trastuzumab; Part 2: lapatinib-trastuzumab combination

therapeutic conventional surgery PROCEDURE

therapeutic conventional surgery

Part 1: Control; Part 2: Control

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• University of Manchester: collaborator
• Manchester University NHS Foundation Trust: collaborator
• Cancer Research UK: collaborator
• Novartis: collaborator

Study Sites (1)

Wythenshawe Hospital

Manchester, England, M23 9LJ, United Kingdom

Location

Related Publications (2)

• Bundred N, Cameron D, Armstrong A, Brunt AM, Cramer A, Dodwell D, Evans A, Hanby A, Hartup S, Hong A., Horgan K, Khattak I, Morden J, Naik J, Narayanan S, Ooi J, Shaaban A, Smith R, Webster-Smith M, Bliss J; on behalf of the EPHOS-B investigators. Effects of perioperative lapatinib and trastuzumab alone in combination in early HER2+ breast cancer - results from the EPHOS-B trial (CRUK/08/002). Eur J Cancer Supplements. 2016; 57 (Suppl 2): S5 #6LBA.

  BACKGROUND

• Bliss JM, Robison LE, Webster-Smith MF, Emson MA, Kilburn LS, Smith IE, Robertson J, Dowsett M, Bundred NJ, Cameron DA, Vidya R, Horgan K, Evans AA, Kokan JS, Pinhel I, A'Hern R; on behalf of the POETIC and EPHOS-B Trialists. A trial model for the future in the search for personalised medicine - the UK POETIC and EPHOS-B perioperative trials experience. Cancer Res. 2011; 71(24 Suppl): Abstract number OT2-03-04.

  BACKGROUND

Related Links

• Cancer Research UK - lay summary of EPHOS-B
• ISRCTN Registry

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Lapatinib; Chemotherapy, Adjuvant; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Nigel Bundred

  Wythenshawe Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: April 15, 2010
• Study Start: April 1, 2010
• Primary Completion: August 30, 2017
• Study Completion: September 1, 2025
• Last Updated: September 17, 2018

Record last verified: 2018-02

Locations

GB (1)