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Neoplasms, BreastPhase 2ELATENCT01205217

Lapatinib or Trastuzumab Given Prior to Surgery With Chemotherapy in Patients With Early Breast Cancer

A Phase 2 study testing Lapatinib, Trastuzumab and Epirubicin in people with Neoplasms, Breast, run by GlaxoSmithKline at 6 sites in 4 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This study will test the safety of a drug called lapatinib and how well it works. Lapatinib (also called Tyverb or Tykerb) will be compared with another drug trastuzumab (also called Herceptin). Trastuzumab is an antibody against the HER2 protein. It binds to part of the HER2 protein to stop it working. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Neoplasms, Breast
What is being tested?
Lapatinib, Trastuzumab and Epirubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
6 sitesin 4 countries
Study dates
Dec 2010to Dec 2010
Phase
Phase 2
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

  • Signed written informed consent approved by an Independent Ethics Committee (IEC) and obtained prior to any study specific screening procedures.
  • Female patients aged ≥18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 -1.
  • Histologically confirmed, previously untreated, operable Stage I-IIIA invasive breast cancer:
  • Primary tumour greater than 1 cm in diameter measured by clinical examination and confirmed by at least one imaging study (mammography, breast ultrasound or MRI).
  • In the case of a multifocal tumour (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be >1 cm and is designated as the "target" lesion for all subsequent tumour evaluations.
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  • Over expression and/or amplification of ErbB2 in the invasive component of the primary tumour according to one of the following definitions. Central laboratory confirmation is not required prior to randomization, but tumour samples must be available for banking and retrospective confirmation.
  • 3+ over expression by IHC (>30% of invasive tumour cells);
  • 2+ or 3+ (in 30% or less neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating ErbB2 gene amplification;
  • ErbB2 gene amplification by FISH/CISH (>6 ErbB2 gene copies per nucleus, or a FISH ratio [ErbB2 gene copies to chromosome 17 signals] of >2.2.) Patients with a negative or equivocal overall result (FISH test ratio of ≤2.2, ≤6.0 ErbB2 gene copies per nucleus) and staining scores of 0,1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are NOT eligible for participation in the trial.
  • Known ER and PgR hormone receptor status.
  • LVEF within institutional normal range (evaluated by multiple-gated acquisition [MUGA] or echocardiography).
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days (preferably 7 days) of first dose of study treatment and agree to use effective contraception, as defined in Section 7.3.2, during the study and for 28 days following the last dose of study drug.
  • Adequate baseline organ function defined by:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,
  • Hemoglobin ≥ 9 g/dL,
  • Platelet count ≥ 100 x 109/L,
  • Serum bilirubin ≤1.5 x ULN. In the case of known Gilbert´s syndrome, < 2x ULN is allowed,
  • ALT and AST ≤ 2.5 x ULN,
  • Alkaline phosphatase ≤ 2.5 x ULN,
  • Serum creatinine ≤ 1.6 mg/dL or calculated creatinine (Cockcroft and Gault ) clearance ≥50mL/m.
  • Patient agrees to make available tumour tissue samples for submission to the central laboratory for planned as well as future translational research.
  • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
  • -

Who cannot join

  • Metastatic, locally advanced, or inflammatory breast cancer as defined by the AJCC (7th Edition).
  • Bilateral breast cancer.
  • Multicentric breast cancer (defined as the presence of two or more foci of cancer in different quadrants of the same breast).
  • Any prior treatment for primary breast cancer (other than excision of tumour in the contralateral breast, and provided that the patient did not previously receive adjuvant radiotherapy or chemotherapy, all of which exclude the patient).
  • Concurrent participation in another clinical trial involving anti-cancer investigational drug or administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
  • History of any prior malignancy in previous 5 years (patients with a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ of the cervix are eligible).
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  • History of significant comorbidities that interfere with the conduct of the study, or evaluation of the results, or with informed consent.
  • Active infection.
  • Peptic ulcer or unstable diabetes mellitus within 8 weeks prior to study enrolment.
  • Clinically significant (i.e. active) cardiovascular disease, including cerebrovascular accident (≤6 months before enrolment), myocardial infarction (≤6 months before enrolment), unstable angina, New York Heart Association (NYHA) ≥ grade 2 congestive heart failure, serious cardiac arrhythmia requiring medication during the study and that might interfere with regularity of the study treatment, or not controlled by medication.
  • Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
  • Lactating women.
  • Subjects unable to swallow and retain orally administered medication or with any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome, major resection of the stomach or bowels, or ulcerative colitis are also excluded.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to any of the study drugs, active ingredients, or excipients that contraindicates their participation.
  • Concomitant use of CYP3A4 inhibitors or inducers.
  • -

Trial locations and contacts

6 sites in 4 countries.

6 sites in 4 countries

Hungary2 sites

  • GSK Investigational Site

    Budapest, 1122

  • GSK Investigational Site

    Gyula, 5700

Other trials in Hungary

Norway2 sites

  • GSK Investigational Site

    Oslo, 0310

  • GSK Investigational Site

    Oslo, 0407

Other trials in Norway

Austria1 site

  • GSK Investigational Site

    Graz, A-8036

Other trials in Austria

Spain1 site

  • GSK Investigational Site

    Castellon, 12002

Other trials in Spain

About this study

Official title: Randomized Study of Efficacy & Safety of Lapatinib & Epirubicin & Cyclophosphamide (EC90) Followed by Paclitaxel & Lapatinib Compared With EC90 Followed by Paclitaxel & Trastuzumab, as Neoadjuvant Therapy in Patients With Previously Untreated ErbB2-overexpressing Stage I - IIIA Breast Cancer.

This study will test the safety of a drug called lapatinib and how well it works. Lapatinib (also called Tyverb or Tykerb) will be compared with another drug trastuzumab (also called Herceptin).

Trastuzumab is an antibody against the HER2 protein. It binds to part of the HER2 protein to stop it working. Clinical trials have found that adding trastuzumab to chemotherapy lowers the rate of cancer recurrence and improves survival in women with HER2 positive breast cancer.

Read more

Lapatinib also stops the HER2 protein working and may slow or stop cancer cells from growing and may prevent cancer from returning. Lapatinib has been approved in some countries to treat patients with certain types of breast cancer. However lapatinib has not been approved to treat early breast cancer. This study is one of many being carried out involving lapatinib in early breast cancer and these studies are showing that it is a promising treatment.

This study will compare lapatinib and trastuzumab. One group of people will take lapatinib and another group will take trastuzumab. The effects of the drugs, both good and bad, will be compared. This study will compare two different durations of HER2 treatment to see if earlier introduction of HER2 treatment is beneficial. The lapatinib group will receive HER2 treatment from the very beginning for 24 weeks prior to surgery and the trastuzumab group will only receive HER2 therapy for 12 weeks prior to surgery.

Read the detailed description

This is a randomized, parallel-arm, open-label, multicentre, Phase II study to determine the efficacy and safety of lapatinib in combination with epirubicin and cyclophosphamide (EC90-L) followed by paclitaxel and lapatinib (PX-L) compared with EC90 followed by paclitaxel and trastuzumab (PX-T) as systemic neoadjuvant therapy for patients with previously untreated, operable, ErbB2-overexpressing, Stage I- IIIA breast cancer.

Approximately 164 subjects will be enrolled in the study. Subjects will be randomised in a 1:1 ratio and stratified according to the following factors, each of which must be established prior to commencing randomisation:

  • Tumour size (≤ 2 cm versus >2 cm in diameter).
  • Locally determined ER status (either ER positive or negative).

Patients will be randomised to one of two treatment arms and will receive the following study treatments:

Arm A: Experimental Arm (n=82) Part I (Week 1-12) Epirubicin 90 mg/m2 by IV infusion on Day 1 every 21 days Cyclophosphamide 600 mg/m2 by IV infusion on Day 1 every 21 days Lapatinib 1000 mg orally once daily continuously Loperamide as required for the proactive management of diarrhoea (see Section 5.13.6)

Part II (Week 13-24) Paclitaxel 80 mg/m2 by IV infusion on Day 1 of each week Lapatinib 1000 mg orally once daily continuously Loperamide as required for the proactive management of diarrhoea (see Section 5.13.6)

Arm B: Reference Arm (n=82):

Part I (Week 1-12) Epirubicin 90 mg/m2 by IV infusion on Day 1 every 21 days Cyclophosphamide 600 mg/m2 by IV infusion on Day 1 every 21 days Part II (Week 13-24) Paclitaxel 80 mg/m2 by IV infusion on Day 1 of each week Trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV Day 1 of each week

The primary study period includes the screening phase, administration of randomized neo-adjuvant study treatment, and assessments up to the primary endpoint assessment at the time of definitive breast cancer surgery.

Keywords
lapatinib, epirubicin, cyclophosphamide, trastuzumab, paclitaxel, neoadjuvant therapy, 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.

  • LapatinibDrug

    Lapatinib 1000 mg orally once daily continuously

  • TrastuzumabDrug

    Part II (Week 13-24) Trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV Day 1 of each week

  • EpirubicinDrug

    Part I (Week 1-12) Epirubicin 90 mg/m2 by IV infusion on Day 1 every 21 days

  • CyclophosphamideDrug

    Part I (Week 1-12) Cyclophosphamide 600 mg/m2 by IV infusion on Day 1 every 21 days

  • PaclitaxelDrug

    Part II (Week 13-24) Paclitaxel 80 mg/m2 by IV infusion on Day 1 of each week

Study groups in NCT01205217
Study groupRoleWhat they receive
Arm AExperimentalLapatinib in combination with epirubicin and cyclophosphamide followed by paclitaxel and lapatinib. Part I (Week 1-12) Epirubicin 90 mg/m2 by IV infusion on Day 1 every 21 days Cyclophosphamide 600 mg/m2 by IV infusion on Day 1 every 21 days Lapatinib 1000 mg orally once daily continuously Loperamide as required for the proactive management of diarrhoea Part II (Week 13-24) Paclitaxel 80 mg/m2 by IV infusion on Day 1 of each week Lapatinib 1000 mg orally once daily continuously Loperamide as required for the proactive management of diarrhoea
Receives: Drug: Lapatinib; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel
Arm BActive comparatorEpirubicin and cyclophosphamide followed by paclitaxel and trastuzumab. Part I (Week 1-12) Epirubicin 90 mg/m2 by IV infusion on Day 1 every 21 days Cyclophosphamide 600 mg/m2 by IV infusion on Day 1 every 21 days Part II (Week 13-24) Paclitaxel 80 mg/m2 by IV infusion on Day 1 of each week Trastuzumab 4 mg/kg IV load followed by 2 mg/kg IV Day 1 of each week
Receives: Drug: Trastuzumab; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic complete response (pCR) in the breast

    Measured: At the time of definitive surgery

Secondary outcomes (3)

  1. pCR rate in the breast and axilla

    Measured: At the time of definitive surgery

  2. Overall response rate (complete plus partial response) in the breast and axilla according to RECIST 1.1 criteria

    Measured: This will be measured at week 13 and post treatment prior to surgery

  3. The breast conservation rate

    Measured: At the time of definitive surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2010 (estimated)
  2. Study startDec 2010
  3. Primary completionDec 2010
  4. Study completionDec 2010 (estimated)

Why it stopped: Data presented at SABCS 2010 showing that dual blockade is superior to monotherapy

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01205217
Sponsor's protocol ID
113957
Acronym
ELATE
Status last verified
Jun 2017
First submitted
17 Sep 2010
Last updated
7 Jun 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib, Trastuzumab and Epirubicin in people with Neoplasms, Breast, run by GlaxoSmithKline at 6 sites in 4 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 24 inclusion and 17 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: withdrawn, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Hungary, Norway, Austria, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Pathologic complete response (pCR) in the breast (time frame: At the time of definitive surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01205217.

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 7 Jun 2017.

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