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ALTTO(Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation)Study; BIG 2-06/N063D

Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase
 Type
 Status
 Age
 Sponsor
 Protocol IDs

Phase III
Treatment
Active
18 and over
NCI, Pharmaceutical / Industry
EGF106708
BIG 2-06/N063D/MAC13, NCT00490139

Trial Description

Summary

This is a randomised, open label multi-centre phase III study comparing the activity of lapatinib alone versus trastuzumab alone versus trastuzumab followed by lapatinib versus lapatinib concomitantly with trastuzumab in the adjuvant treatment of patients with ErbB2 overexpressing and/or amplified breast cancer.

Eligibility Criteria

INCLUSION CRITERIA:

  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status ≥1;
  • Non-metastatic operable primary invasive adenocarcinoma of the breast fulfilling the following:

1. Histologically confirmed;

2. Adequately excised (exceptions: patients who have 'non-resectable' deep margin invasion are eligible provided they have had or will receive radiotherapy encompassing the region concerned; patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumour bed);

3. Axilla dissected; sentinel node sampling is allowed provided that axillary dissection follows confirmation of a positive sentinel node; sentinel node sampling alone is NOT acceptable after neoadjuvant chemotherapy (in patients receiving neoadjuvant chemotherapy lymph node status will be considered unknown, regardless of the results of post-chemotherapy axillary dissection);

4. Axillary node positive patient OR node negative patient with a tumour greater than or equal to 1.0 cm in greatest diameter (≥ T1c) according to TNM.

  • Known hormone receptor status (ER/PgR or ER alone);
  • Must have received at least four cycles of an approved anthracycline-based (neo-) adjuvant chemotherapy regimen.

For design 1: Randomisation must be performed no longer than 12 weeks from day 1 of the last chemotherapy cycle after obtaining a post-chemotherapy LVEF ≥ 50. Study treatment should start no more than 14 days after randomisation.

For design 2: Randomisation must be performed no longer than 6 weeks from day 1 of the last anthracycline-containing chemotherapy cycle after obtaining a post-anthracycline chemotherapy LVEF ≥ 50. Study treatment should start no more than 14 days after randomization and must be concurrent with paclitaxel.

  • Baseline LVEF ≥50% measured by echocardiography or MUGA scan after completion of all anthracycline-based (neo-) adjuvant chemotherapy and prior to the targeted therapy(ies).
  • Over expression and/or amplification of HER2 in the invasive component of the primary tumour (in case of neoadjuvant treatment, tissue sample used for HER2 testing should be collected before neoadjuvant treatment starts), according to one of the following definitions [Wolff et al 2007] and confirmed by central laboratory prior to randomisation:
  • 3+ over expression by IHC (> 30% of invasive tumour cells);
  • 2+ or 3+ (in 30% or less neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification;
  • HER2 gene amplification by FISH/CISH ( > 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of > than 2.2.) Patients with a negative or equivocal overall result (FISH test ratio of < 2.2, < 6.0 HER2 gene copies per nucleus) and staining scores of 0,1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible for participation in the trial.

Equivocal local results may be submitted for a final determination by the central laboratory.

  • Completion of all necessary baseline laboratory and radiological investigations
  • Signed written informed consent (approved by an Independent Ethics Committee (IEC) and obtained prior to any study specific screening procedures).

EXCLUSION CRITERIA:

  • History of any prior (ipsi- and/or contralateral) invasive breast carcinoma;
  • Past or current history of malignant neoplasms, except for curatively treated: - Basal and squamous cell carcinoma of the skin;- Carcinoma in situ of the cervix
  • Any clinically staged T4 tumour, including inflammatory breast cancer;
  • Bilateral tumours;
  • Multifocal tumours;
  • Maximum cumulative dose of doxorubicin >360mg/m² or maximum cumulative dose of epirubicin >720mg/m² or any prior anthracyclines unrelated to the present breast cancer;
  • (Neo-) or adjuvant chemotherapy using peripheral stem cell or bone marrow stem cell support;
  • Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer;
  • Patients with positive or suspicious internal mammary nodes identified by sentinel node technique which have not been irradiated or will not be irradiated, or patients with supraclavicular lymph node involvement (confirmed by fine needle aspirate or biopsy);
  • Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for breast cancer;
  • Concurrent anti-cancer treatment, except hormonal therapy;
  • Concurrent anti-cancer treatment in another investigational trial with hormone therapy or immunotherapy:
  • Serious cardiac illness or medical conditions including but not confined to:

History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%); High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled); Angina pectoris requiring antianginal medication; Clinically significant valvular heart disease; Evidence of transmural infarction on ECG; Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg);

  • Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness;
  • Any of the following abnormal laboratory tests immediately prior to randomisation:

serum total bilirubin >2.0 x upper limit of normal (ULN); alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) >2.5 x ULN; alkaline phosphatase (ALP) > 2.5 x ULN; serum creatinine >2.0 x ULN; total white blood cell count (WBC) <2.5 x 10^9/L; absolute neutrophil count <1.5 x 10^9/L; platelets <100 x 10^9/L.

  • Unresolved or unstable serious adverse events from prior adjuvant chemotherapy or radiotherapy;
  • Malabsorption syndrome, any disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or persons unable to swallow oral medication. Subjects with ulcerative colitis are also excluded;
  • Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test - urine or serum - within 7 days prior to randomisation);
  • Women of childbearing potential and male participants with partners of child bearing potential, including women whose last menstrual period was <1 year ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during study treatment (adequate contraceptive measures: intra-uterine device, barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not indicated in this patient population);
  • Concomitant use of CYP3A4 inhibitors or inducers.

Trial Contact Information

Trial Lead Organizations/Sponsors

GlaxoSmithkline

Breast International Group

North Central Cancer Treatment Group

National Cancer Institute

NCIC-Clinical Trials Group

GSK Clinical Trials, MDPrincipal Investigator

Trial Sites

U.S.A.
Arizona
  Scottsdale
 GSK Clinical Trials Call Center
 Edith Perez Ph: 877-379-3718
Arkansas
  Jonesboro
 GSK Clinical Trials Call Center
 Carroll Scroggin Ph: 877-379-3718
Florida
  Fort Myers
 GSK Clinical Trials Call Center
 Thomas Ervin Ph: 877-379-3718
  Jacksonville
 GSK Clinical Trials Call Center
 Edith Perez Ph: 877-379-3718
Iowa
  Ames
 GSK Clinical Trials Call Center
 Joseph Merchant Ph: 877-379-3718
  Cedar Rapids
 GSK Clinical Trials Call Center
 Martin Wiesenfeld Ph: 877-379-3718
  Mason City
 GSK Clinical Trials Call Center
 Walter Bate Ph: 877-379-3718
Minnesota
  Rochester
 GSK Clinical Trials Call Center
 Edith Perez Ph: 877-379-3718
North Carolina
  Kinston
 GSK Clinical Trials Call Center
 Peter Watson Ph: 877-379-3718
North Dakota
  Bismarck
 GSK Clinical Trials Call Center
 Edward Wos Ph: 877-379-3718
Ohio
  Cincinnati
 GSK Clinial Trials Call Center
 Patrick Ward Ph: 877-379-3718
Tennessee
  Chattanooga
 GSK Clinical Trials Call Center
 Brooke Daniel Ph: 877-379-3718
  Nashville
 GSK Clinical Trials Call Center
 Denise Yardley Ph: 877-379-3718
Virginia
  Richmond
 GSK Clinical Trials Call Center
 David Trent Ph: 877-379-3718
Argentina
  Landstuhl
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Roth
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
Australia
  Hobart
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
Belgium
  Antwerpen
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Bonheiden
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Brasschaat
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Brugge
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Brussel
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Bruxelles
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Charleroi
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Edegem
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Gent
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Haine Saint Paul
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Hasselt
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Huy
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Kortrijk
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Leuven
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Liege
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Mons
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Namur
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Roeselare
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Sint-Niklaas
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Tournai
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Turnhout
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Verviers
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Wilrijk
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Yvoir
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
Chile
  Valparaiso
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Viña del Mar
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
China
  Beijing
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
Czech Republic
  Brno
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Ceske Budejovice
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Chomutov
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Jihlava
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Novy Jicin
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Olomouc
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Pardubice
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Praha 10
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Praha 2
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Praha 4
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Praha 5
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Usti nad Labem
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
Denmark
  Aalborg
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Arhus C
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Esbjerg
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Herlev
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Hilleroed
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Koebenhavn
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Naestved
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Odense C
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Roskilde
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Vejle
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Viborg
 G
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
France
  Annecy
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Bayonne
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Bordeaux
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Caen
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Dijon Cedex
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Grenoble cedex 02
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Hyeres
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Le Chesnay
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  le Havre
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Le Mans
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Lyon
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Montbeliard
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Nice Cedex 2
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Perigueux
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Rouen Cedex 1
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Saint Gregoire
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Saint-Brieuc
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Saint-Priest en Jarez
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Toulouse
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Villejuif Cedex
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
Germany
  Aalen
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Aschaffenburg
 GSK Clinical Trials Call Centre
 GSK Clinical Trials Call Centre Ph: 1 877 379 3718
  Aschersleben