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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by ICORG- All Ireland Cooperative Oncology Research Group
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group Identifier:
First received: February 1, 2012
Last updated: August 11, 2014
Last verified: August 2014

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 Intervention Phase
Metastatic Breast Cancer
Drug: Trastuzumab
Drug: Paclitaxel
Drug: Lapatinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: January 2012
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Ages Eligible for Study:   18 Years and older
Genders 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01526369

  Hide Study Locations
Helsinki University Hopsital Recruiting
Helsinki, Finland
Contact: Contact Person    + 358 04711 2010      
Principal Investigator: Johanna Mattson, Prof         
Kuopio University hospital Recruiting
Kuopio, Finland
Contact: Contact person    01-6677211      
Principal Investigator: Vesa Kataja, Prof         
CRLC Val d'Aurelle Recruiting
Montpellier, France
Contact: Contact Person    +33 4 6741 0859      
Principal Investigator: Gilles Romieu, Prof         
Interdisziplinäre Onkologische Zentrum München (IOZ München) Recruiting
Munich, Germany
Contact: Contact person    +49 (0)89-599 8888 40      
Principal Investigator: Wolfgang Eiermann, Prof         
St Vincent's University Hospital Recruiting
Dublin, Leinster, Ireland
Contact: John Crown, Prof    01 2094839      
Principal Investigator: John Crown, Prof         
Cork University Hospital Recruiting
Cork, Ireland
Contact: Seamus O'Reilly, Dr    021 4921301      
Principal Investigator: Seamus O'Reilly, Dr         
Beaumont Hospital Recruiting
Dublin, Ireland
Contact: Bryan Hennessy, Dr    01 8092010      
Principal Investigator: Bryan Hennessy, Dr         
Mater Misericordiae University Hospital Recruiting
Dublin, Ireland
Contact: Cathy Kelly, Dr    01 8034835      
Mater Private Hospital Recruiting
Dublin, Ireland
Contact: Catherine Kelly, Dr    01 8034835      
Principal Investigator: Catherine Kelly, Dr         
St James's Hospital Recruiting
Dublin, Ireland
Contact: John Kennedy, Dr    01 4103546      
Principal Investigator: John Kennedy, Dr         
University Hospital Galway Recruiting
Galway, Ireland
Contact: Maccon Keane, Dr    091 544735      
Principal Investigator: Maccon Keane, Dr         
Midwestern Regional Hospital Recruiting
Limerick, Ireland
Contact: Linda Coate, Dr    061482013      
Principal Investigator: Linda Coate, Dr         
Sligo General Hospital Recruiting
Sligo, Ireland
Contact: Michael Martin, Dr    071-9171111      
Principal Investigator: Michael Martin, Dr         
Waterford Regional Hospital Recruiting
Waterford, Ireland
Contact: Miriam O'Connor    051-842000      
Principal Investigator: Miriam O'Connor, Dr         
Rabin Medical Center Recruiting
Petah Tikva, Israel
Contact: Contact Person    03-9376363      
Principal Investigator: Salomon M Stemmer, Dr         
The Chaim Sheba Medical Center Recruiting
Tel Hashomer, Israel
Contact: Contact person    +972-3-530-3030      
Principal Investigator: Shani Simon Paluch, Dr         
Oslo University Hopsital Recruiting
Oslo, Norway
Contact: Contact Person    01-6677211      
Principal Investigator: Anna Barbro Saetersdal, Dr         
Hospital Santa Maria Recruiting
Lisbon, Portugal
Contact: Contact Person    021-7805000      
Principal Investigator: Luis Costa, Prof         
Complejo Hospitalario de Jaen Recruiting
Andalucia, Spain
Contact: Contact Person    0953008000      
Principal Investigator: Pedro S Rovira, Dr         
Hospital Nuestra Senora de Sonsoles Recruiting
Avila, Spain
Contact: Contact Person    0920223367      
Principal Investigator: Jose E Ales, Dr         
Hospital Infanta Cristina Recruiting
Badajoz, Spain
Contact: Contact Person    0924218111      
Principal Investigator: Esperanza Blanco, Dr         
Hospital Universitario de Canarias Recruiting
Canarias, Spain
Contact: Contact Person    0922678000      
Principal Investigator: Jose N.B. Lopez, Dr         
Hospital Universitari Arnau de Vilanova de Lleida Recruiting
Cataluna, Spain
Contact: Contact Person    0973248100      
Principal Investigator: Serafin M Murillo, Dr         
Hospital Virgen de la Luz Recruiting
Cuenca, Spain
Contact: Contact Person    0969179900      
Principal Investigator: Medel Mar Munoz, Dr         
Centro Oncologico de Galicia Recruiting
Galicia, Spain
Contact: Contact Person    0981287499      
Principal Investigator: Manuel R Vazquez, Dr         
Hospital General de Grannollers Recruiting
Granollers, Spain
Contact: Contact Person    0938425000      
Principal Investigator: Laura J Lopez, Dr         
Complejo Hospitalario Xeral Calde / Hospital Lucus Augusti Recruiting
Lugo, Spain
Contact: Contact Person    0982296000      
Principal Investigator: Elena Alvarez, Dr         
H. Puerta de Hierro Recruiting
Madrid, Spain
Contact: Contact Person    0911916000      
Principal Investigator: Blanca Cantos, Dr         
Hospital General Universitario Gregorio Maranon Recruiting
Madrid, Spain
Contact: Contact Person    0915868000      
Principal Investigator: Miguel Martin, Dr         
Hospital de Mataro Recruiting
Mataro, Spain
Contact: Contact Person    0937417700      
Principal Investigator: Montserrat V Capellas, Dr         
Hospital Donostia Not yet recruiting
Pais Vasco, Spain
Contact: Contact Person    0943007000      
Principal Investigator: Isabel A Lopez, Dr         
Hospital Infanta Cristina Recruiting
Parla, Spain
Contact: Contact Person    0924218111      
Principal Investigator: Coralia Bueno, Dr         
Hospital General Universitario de Elche Not yet recruiting
Valencia, Spain
Contact: Contact Person    0966616900      
Principal Investigator: Alvaro R Lescure, Dr         
Hospital General Universitario de Valencia Recruiting
Valencia, Spain
Contact: Contact Person    0961972000      
Principal Investigator: Vega Iranzo, Dr         
Hospital Clinico Universitario 'Lozano Blesa' Recruiting
Zaragoza, Spain
Contact: Contact Person    0976765700      
Principal Investigator: Raquel Andres, Dr         
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
  More Information

No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group Identifier: NCT01526369     History of Changes
Other Study ID Numbers: ICORG 11-10
Study First Received: February 1, 2012
Last Updated: August 11, 2014
Health Authority: Ireland: Irish Medicines Board

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
HER2-positive metastatic breast cancer.

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators processed this record on November 27, 2014