Metastatic Breast CancerPhase 3TH V THLNCT01526369
A Randomized Study of TH Versus THL in First Line Treatment of HER2-positive Metastatic Breast Cancer
A Phase 3 study testing Trastuzumab, Paclitaxel and Lapatinib in people with Metastatic Breast Cancer, run by Cancer Trials Ireland at 35 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Trastuzumab, Paclitaxel and Lapatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 35 sitesin 8 countries
- Study dates
- 13 Feb 2012to 17 Feb 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 19Show fewer
- 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
- Serum creatinine ≤1.5 ULN or calculated creatinine clearance (CrCl) ≥ 30mL/min according to the Cockcroft and Gault formula (Appendix K)
- Able to swallow and retain oral medication.
- 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.
- Estimated life expectancy greater than 12 weeks
Who cannot join
- 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
Show all 16Show fewer
- 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)
- Concurrent treatment with ovarian hormone replacement therapy. Prior treatment must be stopped prior to registration.
Trial locations and contacts
35 sites in 8 countries.
35 sites in 8 countries
Spain17 sites
Centro Oncologico de Galicia
A Coruña
Hospital Nuestra Senora de Sonsoles
Ávila
Hospital Infanta Cristina
Badajoz
Hospital Virgen de la Luz
Cuenca
Hospital General de Grannollers
Granollers
Complejo Hospitalario de Jaen
Jaén
Hospital Universitari Arnau de Vilanova de Lleida
Lleida
Complejo Hospitalario Xeral Calde / Hospital Lucus Augusti
Lugo
H. Puerta de Hierro
Madrid
Hospital General Universitario Gregorio Maranon
Madrid
Hospital de Mataro
Mataró
Hospital Infanta Cristina
Parla
Hospital Donostia
San Sebastián
Hospital Universitario de Canarias
Santa Cruz de Tenerife
Hospital General Universitario de Elche
Valencia
Hospital General Universitario de Valencia
Valencia
Hospital Clinico Universitario 'Lozano Blesa'
Zaragoza
Ireland10 sites
Cork University Hospital
Cork
St Vincent's University Hospital
Dublin, Leinster
Beaumont Hospital
Dublin
Mater Misericordiae University Hospital
Dublin
Mater Private Hospital
Dublin
St James's Hospital
Dublin
University Hospital Galway
Galway
Midwestern Regional Hospital
Limerick
Sligo General Hospital
Sligo
Waterford Regional Hospital
Waterford
Finland2 sites
Helsinki University Hopsital
Helsinki
Kuopio University hospital
Kuopio
Israel2 sites
Rabin Medical Center
Petah Tikva
The Chaim Sheba Medical Center
Tel HaShomer
Germany1 site
Interdisziplinäre Onkologische Zentrum München (IOZ München)
Munich
About this study
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
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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Trastuzumab, Paclitaxel, Lapatinib
- Keywords
- HER2-positive metastatic breast cancer.
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
PaclitaxelDrug
LapatinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Paclitaxel and Trastuzumab | Active comparator | 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. Receives: Drug: Trastuzumab; Drug: Paclitaxel |
| Paclitaxel, Trastuzumab and Lapatinib | Experimental | 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. Receives: Drug: Trastuzumab; Drug: Paclitaxel; Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Measured: 9 months
Secondary outcomes (1)
Overall Survival
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2012 (estimated)
- Study start13 Feb 2012
- Primary completionNov 2015
- Study completion17 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Trials Ireland
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01526369
- Sponsor's protocol ID
- CTRIAL-IE (ICORG) 11-10
- Acronym
- TH V THL
- Status last verified
- May 2025
- First submitted
- 1 Feb 2012
- Last updated
- 9 May 2025
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01526369
- Acronym / sponsor ID
- TH V THL / CTRIAL-IE (ICORG) 11-10
- Conditions
- Metastatic Breast Cancer
- Keywords
- HER2-positive metastatic breast cancer.
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Cancer Trials IrelandResearch network
- Study start
- 13 Feb 2012 (actual)
- Primary completion
- Nov 2015 (actual)
- Study completion
- 17 Feb 2023 (actual)
- First posted
- 3 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paclitaxel and Trastuzumab | Active comparator | Drug: Trastuzumab, Drug: PaclitaxelWeekly 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 | Experimental | Drug: Trastuzumab, Drug: Paclitaxel, Drug: LapatinibWeekly 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab | Drug | Paclitaxel and Trastuzumab, Paclitaxel, Trastuzumab and Lapatinib |
| Paclitaxel | Drug | Paclitaxel and Trastuzumab, Paclitaxel, Trastuzumab and Lapatinib |
| Lapatinib | Drug | Paclitaxel, Trastuzumab and Lapatinib |
Primary outcome
Progression Free Survival
Time frame: 9 months
1 secondary outcome
Overall Survival
Time frame: 30 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2025.
Related trials for Metastatic Breast Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 3
ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer
Breast Neoplasms
Active, not recruitingPhase 2
Phase II Study of Dato-DXd in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases
Breast Cancer Stage IV
RecruitingPhase 2
Functional Precision Oncology to Predict, Prevent, and Treat Early Metastatic Recurrence of TNBC
Breast Cancer Recurrent
RecruitingPhase 1
Study of XB010 in Subjects With Solid Tumors
Locally Advanced or Metastatic Solid Tumors, Esophageal Squamous Cell Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trastuzumab, Paclitaxel and Lapatinib in people with Metastatic Breast Cancer, run by Cancer Trials Ireland at 35 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in Spain, Ireland, Finland, Israel, France and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2025.