ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D (ALTTO)
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ClinicalTrials.gov Identifier: NCT00490139 |
Recruitment Status :
Completed
First Posted : June 22, 2007
Results First Posted : August 18, 2014
Last Update Posted : July 23, 2021
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Tracking Information | |||||
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First Submitted Date ICMJE | June 20, 2007 | ||||
First Posted Date ICMJE | June 22, 2007 | ||||
Results First Submitted Date ICMJE | July 30, 2014 | ||||
Results First Posted Date ICMJE | August 18, 2014 | ||||
Last Update Posted Date | July 23, 2021 | ||||
Actual Study Start Date ICMJE | May 16, 2007 | ||||
Actual Primary Completion Date | December 6, 2013 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Disease-free Survival (DFS) [ Time Frame: From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years) ] Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer (SPC), or death from any cause. DFS was estimated using the Kaplan Meier method.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who had disease free survival for the indicated years.
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Original Primary Outcome Measures ICMJE |
Disease-free survival will be analysed after 1386 events, using a two-sided stratified log-rank test. | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
Overall survival, Time to recurrence, Time to distant recurrence will be analysed using Kaplan Meirer plots. | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D | ||||
Official Title ICMJE | A Randomised, Multi-centre, Open-label, Phase III Study of Adjuvant Lapatinib, Trastuzumab, Their Sequence and Their Combination in Patients With HER2/ErbB2 Positive Primary Breast Cancer | ||||
Brief 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. Patients will be enrolled according to one of two design schemas, with Design 2 having two chemotherapy options (Design 2 and 2B), and will be randomised to one of four treatment regimens within each design schema. The primary objective of this study is to compare disease-free survival (DFS) in patients with HER2 overexpressing and/or amplified breast cancer randomised to trastuzumab for one year versus lapatinib for one year versus trastuzumab (12 or 18 weeks, according to assigned design) followed by a six-week treatment-free interval followed by lapatinib (28 or 34 weeks, according to assigned design) versus trastuzumab in combination with lapatinib for one year (52 weeks). Secondary objectives include treatment comparisons with respect to overall survival, time to recurrence, time to distant recurrence, safety and tolerability, incidence of brain metastasis, and analyses conducted separately for cohorts of patients defined by presence or absence of cMyc oncogene amplification, expression level of PTEN and presence or absence of the p95HER2 receptor. On August 18, 2011, the ALTTO Independent Data Monitoring Committee (IDMC) met to review the first planned interim analysis. The IDMC reported that the comparison of lapatinib alone versus trastuzumab alone crossed the futility boundary, indicating that the lapatinib alone arm was unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival (DFS). The IDMC also stated that the other three arms (trastuzumab alone, sequential trastuzumab/lapatinib arm and the combination arm) should continue as planned with no changes. |
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Detailed Description | Not Provided | ||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 3 | ||||
Study Design ICMJE | Allocation: Randomized Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Neoplasms, Breast | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
8382 | ||||
Original Enrollment ICMJE |
8000 | ||||
Actual Study Completion Date ICMJE | July 1, 2021 | ||||
Actual Primary Completion Date | December 6, 2013 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
For Design 1: Randomization 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 must start no more than 14 days after randomization For Design 2: Randomization 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 must start no more than 14 days after randomization and must be concurrent with taxanes. For Design 2B: Randomisation must be performed no longer than 8 weeks from definitive surgery. Non-anthracycline platinum containing regimen (docetaxel and carboplatin) and study treatment must start concomitantly and no more than 14 days after randomisation.
Equivocal local results may be submitted for a final determination by the central laboratory.
Exclusion Criteria:
NOTE: Patients with a prior malignancy diagnosed greater than 10 years in the past who have been curatively treated with surgery ONLY, WITHOUT radiation therapy or systemic therapy (chemotherapy or endocrine) are eligible for the study. Patients with any prior diagnosis of breast cancer or melanoma, at any time, are excluded from this study.
NOTE: multifocal/multicentric tumours are permitted:
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);
serum total bilirubin >1.5 x upper limit of normal (ULN), in the case of known Gilbert's syndrome, a higher serum total bilirubin (<2 X ULN) is allowed; 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.
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Czechia, Denmark, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Norway, Pakistan, Peru, Philippines, Poland, Romania, Russian Federation, Singapore, Slovakia, Slovenia, South Africa, Spain, Switzerland, Taiwan, Thailand, Ukraine, United Kingdom, United States | ||||
Removed Location Countries | Czech Republic, Luxembourg, Portugal, Sweden, Turkey | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT00490139 | ||||
Other Study ID Numbers ICMJE | EGF106708 CLAP016B2301 ( Other Identifier: Novartis ) 2006-000562-36 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Novartis ( Novartis Pharmaceuticals ) | ||||
Original Responsible Party | Not Provided | ||||
Current Study Sponsor ICMJE | Novartis Pharmaceuticals | ||||
Original Study Sponsor ICMJE | GlaxoSmithKline | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Novartis | ||||
Verification Date | July 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |