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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.
 
ClinicalTrials.gov Identifier: NCT01526369
Recruitment Status : Active, not recruiting
First Posted : February 3, 2012
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Cancer Trials Ireland

Tracking Information
First Submitted Date  ICMJE February 1, 2012
First Posted Date  ICMJE February 3, 2012
Last Update Posted Date January 21, 2020
Study Start Date  ICMJE January 2012
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2012)
Progression Free Survival [ Time Frame: 9 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2012)
Overall Survival [ Time Frame: 30 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomized Study of TH Versus THL in First Line Treatment of HER2-positive Metastatic Breast Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Breast Cancer
Intervention  ICMJE
  • Drug: Trastuzumab
  • Drug: Paclitaxel
  • Drug: Lapatinib
Study Arms  ICMJE
  • 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.
    Interventions:
    • 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.

    Interventions:
    • Drug: Trastuzumab
    • Drug: Paclitaxel
    • Drug: Lapatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 20, 2015)
75
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2012)
600
Estimated Study Completion Date  ICMJE December 2021
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
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 Finland,   France,   Germany,   Ireland,   Israel,   Norway,   Portugal,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01526369
Other Study ID Numbers  ICMJE CTRIAL-IE (ICORG) 11-10
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cancer Trials Ireland
Study Sponsor  ICMJE Cancer Trials Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Cancer Trials Ireland
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP