A Randomized Study of TH Versus THL in First Line Treatment of HER2-positive Metastatic Breast Cancer (TH V THL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01526369
Recruitment Status : Terminated
First Posted : February 3, 2012
Last Update Posted : May 31, 2017
Information provided by (Responsible Party):
Cancer Trials Ireland

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Trastuzumab Drug: Paclitaxel Drug: Lapatinib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2012
Actual Primary Completion Date : November 2015
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Paclitaxel and Trastuzumab
Weekly 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.
Drug: Trastuzumab Drug: Paclitaxel
Experimental: Paclitaxel, Trastuzumab and Lapatinib

Weekly 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.

Drug: Trastuzumab Drug: Paclitaxel Drug: Lapatinib

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 9 months ]

Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 30 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent obtained prior to any study-related procedures
  2. Female age 18 years or greater.
  3. ECOG Performance Status of 0 or 1.
  4. Histologically or cytologically-confirmed invasive metastatic breast cancer.
  5. 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.
  6. Tumour shows HER2 over-expression (3+ by IHC and/or FISH + ) by testing of the primary tumour and if available the biopsied metastatic lesion
  7. Patients who received prior radiotherapy must have completed it at least 4 weeks before registration and recovered from all treatment-related toxicities.
  8. 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.
  9. 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
    • Serum creatinine ≤1.5 ULN or calculated creatinine clearance (CrCl) ≥ 30mL/min according to the Cockcroft and Gault formula (Appendix K)
  10. Able to swallow and retain oral medication.
  11. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Female patients of childbearing potential must have pregnancy excluded by urine or serum beta-HCG testing within 7 days prior to registration.
  12. Estimated life expectancy greater than 12 weeks

Exclusion Criteria:

  1. Prior systemic therapy for metastatic disease (except one line of hormonal therapy for metastatic disease without trastuzumab).
  2. Recurrence within 12 months from completion of adjuvant chemotherapy to the development of metastatic disease.
  3. Recurrence within 6 months from completion of adjuvant trastuzumab to the development of metastatic disease.
  4. Prior lapatinib treatment.
  5. Peripheral neuropathy ≥ grade 2
  6. Patients with known CNS metastasis should be excluded from this clinical trial
  7. Prior radiotherapy to more than half of the bony pelvis.
  8. 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 .
  9. 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).
  10. Pregnant or breastfeeding women are excluded from this study.
  11. Patients should not be receiving any other investigational agents (within 30 days prior to registration) or receiving concurrent anticancer therapy.
  12. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors (Table 9).
  13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  14. 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).
  15. 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)
  16. Concurrent treatment with ovarian hormone replacement therapy. Prior treatment must be stopped prior to registration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01526369

  Hide Study Locations
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 Hashomer, Israel
Oslo University Hopsital
Oslo, Norway
Hospital Santa Maria
Lisbon, Portugal
Complejo Hospitalario de Jaen
Andalucia, Spain
Hospital Nuestra Senora de Sonsoles
Avila, Spain
Hospital Infanta Cristina
Badajoz, Spain
Hospital Universitario de Canarias
Canarias, Spain
Hospital Universitari Arnau de Vilanova de Lleida
Cataluna, Spain
Hospital Virgen de la Luz
Cuenca, Spain
Centro Oncologico de Galicia
Galicia, Spain
Hospital General de Grannollers
Granollers, 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
Mataro, Spain
Hospital Donostia
Pais Vasco, Spain
Hospital Infanta Cristina
Parla, Spain
Hospital General Universitario de Elche
Valencia, Spain
Hospital General Universitario de Valencia
Valencia, Spain
Hospital Clinico Universitario 'Lozano Blesa'
Zaragoza, Spain
Sponsors and Collaborators
Cancer Trials Ireland

Responsible Party: Cancer Trials Ireland Identifier: NCT01526369     History of Changes
Other Study ID Numbers: CTRIAL-IE (ICORG) 11-10
First Posted: February 3, 2012    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017

Keywords provided by Cancer Trials Ireland:
HER2-positive metastatic breast cancer.

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors