Clinical trial NCT01526369: A Randomized Study of TH Versus THL in First Line Treatment of HER2-positive Metastatic Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Keywords: HER2-positive metastatic breast cancer.
Lead sponsor: Cancer Trials Ireland
Sponsor class: NETWORK
First posted: 2012-02-03
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 9 months
Secondary outcomes:
measure: Overall Survival
timeFrame: 30 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hopsital
city: Kuopio
country: Finland
facility: Kuopio University hospital
city: Montpellier
country: France
facility: CRLC Val d'Aurelle
city: Munich
country: Germany
facility: Interdisziplinäre Onkologische Zentrum München (IOZ München)
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
state: Leinster
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Limerick
country: Ireland
facility: Midwestern Regional Hospital
city: Sligo
country: Ireland
facility: Sligo General Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Oslo
country: Norway
facility: Oslo University Hopsital
city: Lisbon
country: Portugal
facility: Hospital Santa Maria
city: A Coruña
country: Spain
facility: Centro Oncologico de Galicia
city: Avila
country: Spain
facility: Hospital Nuestra Senora de Sonsoles
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Cuenca
country: Spain
facility: Hospital Virgen de la Luz
city: Granollers
country: Spain
facility: Hospital General de Grannollers
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaen
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Lugo
country: Spain
facility: Complejo Hospitalario Xeral Calde / Hospital Lucus Augusti
city: Madrid
country: Spain
facility: H. Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Mataro
country: Spain
facility: Hospital de Mataro
city: Parla
country: Spain
facility: Hospital Infanta Cristina
city: San Sebastián
country: Spain
facility: Hospital Donostia
city: Santa Cruz De Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Valencia
country: Spain
facility: Hospital General Universitario de Elche
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario 'Lozano Blesa'
Study officials:
References: