A Randomized Study of TH Versus THL in First Line Treatment of HER2-positive Metastatic Breast Cancer
TH V THL
A Phase III Randomized Study of TH (Paclitaxel and Trastuzumab) Versus THL (Paclitaxel, Trastuzumab and Lapatinib) in First Line Treatment of HER2-positive Metastatic Breast Cancer
1 other identifier
interventional
75
8 countries
35
Brief Summary
The proposed phase III randomised trial will compare the efficacy of trastuzumab and paclitaxel with trastuzumab, paclitaxel and lapatinib in first line treatment of HER2 positive metastatic breast cancer. The investigators will also examine potential predictive biomarkers of response to trastuzumab and lapatinib in pre-treatment biopsy samples and serum samples.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Feb 2012
Longer than P75 for phase_3
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2012
CompletedFirst Posted
Study publicly available on registry
February 3, 2012
CompletedStudy Start
First participant enrolled
February 13, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
February 17, 2023
CompletedMay 9, 2025
May 1, 2025
3.7 years
February 1, 2012
May 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival
9 months
Secondary Outcomes (1)
Overall Survival
30 months
Study Arms (2)
Paclitaxel and Trastuzumab
ACTIVE COMPARATORWeekly paclitaxel (80mg/m², for 3 weeks of a 4 week cycle) + trastuzumab (8mg/kg loading dose on cycle 1 day 1 and 4mg/kg every 2 weeks) until disease progression, unacceptable toxicity or consent withdrawal.
Paclitaxel, Trastuzumab and Lapatinib
EXPERIMENTALWeekly paclitaxel (80 mg/m², for 3 weeks of a 4 week cycle) + trastuzumab (8 mg/kg loading dose on cycle 1 day 1 and 4 mg/kg every 2 weeks) \+ lapatinib (1,000 mg daily), until disease progression, unacceptable toxicity or consent withdrawal.
Interventions
Eligibility Criteria
You may qualify if:
- Written informed consent obtained prior to any study-related procedures
- Female age 18 years or greater.
- ECOG Performance Status of 0 or 1.
- Histologically or cytologically-confirmed invasive metastatic breast cancer.
- Patients must have measurable disease according to RECIST criteria Version 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan,MRI, or calipers by clinical exam.
- Tumour shows HER2 over-expression (3+ by IHC and/or FISH + ) by testing of the primary tumour and if available the biopsied metastatic lesion
- Patients who received prior radiotherapy must have completed it at least 4 weeks before registration and recovered from all treatment-related toxicities.
- Cardiac ejection fraction within the institutional range of normal as measured by MUGA or ECHO within 14 days prior to registration. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution.
- Adequate haematological, hepatic, and renal function.
- Haemoglobin ≥ 9g/dL
- Neutrophils (ANC/AGC) ≥1500/mm³ (1.5 x 10\^9/L)
- Platelets ≥ (100 x 10\^9/L)
- Total bilirubin ≤ 1.5mg/dL (25.65 μmol/L)
- Both ALT (SGPT) and AST (SGOT) ≤ 3 x ULN with or without liver Metastasis
- Alkaline phosphatase ≤ 2.5 x ULN
- +4 more criteria
You may not qualify if:
- Prior systemic therapy for metastatic disease (except one line of hormonal therapy for metastatic disease without trastuzumab).
- Recurrence within 12 months from completion of adjuvant chemotherapy to the development of metastatic disease.
- Recurrence within 6 months from completion of adjuvant trastuzumab to the development of metastatic disease.
- Prior lapatinib treatment.
- Peripheral neuropathy ≥ grade 2
- Patients with known CNS metastasis should be excluded from this clinical trial
- Prior radiotherapy to more than half of the bony pelvis.
- Uncontrolled or symptomatic angina, uncontrolled arrhythmias, congestive heart failure, a documented MI within 6 months prior to registration or any other cardiac disorders, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient .
- Immediate or delayed hypersensitivity or untoward reaction to paclitaxel, trastuzumab, or other related compounds, or to drugs chemically related to lapatinib (including other anilinoquinazolines, e.g. gefitinib (Iressa®) and erlotinib (Tarceva®), or other chemically-related compounds).
- Pregnant or breastfeeding women are excluded from this study.
- Patients should not be receiving any other investigational agents (within 30 days prior to registration) or receiving concurrent anticancer therapy.
- Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors (Table 9).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
- Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (35)
Helsinki University Hopsital
Helsinki, Finland
Kuopio University hospital
Kuopio, Finland
CRLC Val d'Aurelle
Montpellier, France
Interdisziplinäre Onkologische Zentrum München (IOZ München)
Munich, Germany
St Vincent's University Hospital
Dublin, Leinster, Ireland
Cork University Hospital
Cork, Ireland
Beaumont Hospital
Dublin, Ireland
Mater Misericordiae University Hospital
Dublin, Ireland
Mater Private Hospital
Dublin, Ireland
St James's Hospital
Dublin, Ireland
University Hospital Galway
Galway, Ireland
Midwestern Regional Hospital
Limerick, Ireland
Sligo General Hospital
Sligo, Ireland
Waterford Regional Hospital
Waterford, Ireland
Rabin Medical Center
Petah Tikva, Israel
The Chaim Sheba Medical Center
Tel Litwinsky, Israel
Oslo University Hopsital
Oslo, Norway
Hospital Santa Maria
Lisbon, Portugal
Centro Oncologico de Galicia
A Coruña, Spain
Hospital Nuestra Senora de Sonsoles
Ávila, Spain
Hospital Infanta Cristina
Badajoz, Spain
Hospital Virgen de la Luz
Cuenca, Spain
Hospital General de Grannollers
Granollers, Spain
Complejo Hospitalario de Jaen
Jaén, Spain
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, Spain
Complejo Hospitalario Xeral Calde / Hospital Lucus Augusti
Lugo, Spain
H. Puerta de Hierro
Madrid, Spain
Hospital General Universitario Gregorio Maranon
Madrid, Spain
Hospital de Mataro
Mataró, Spain
Hospital Infanta Cristina
Parla, Spain
Hospital Donostia
San Sebastián, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain
Hospital General Universitario de Elche
Valencia, Spain
Hospital General Universitario de Valencia
Valencia, Spain
Hospital Clinico Universitario 'Lozano Blesa'
Zaragoza, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2012
First Posted
February 3, 2012
Study Start
February 13, 2012
Primary Completion
November 1, 2015
Study Completion
February 17, 2023
Last Updated
May 9, 2025
Record last verified: 2025-05