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Neoplasms, BreastPhase 2NCT00524303

Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.

A Phase 2 study testing Trastuzumab, Paclitaxel and FEC75 in people with Neoplasms, Breast, run by GlaxoSmithKline at 23 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will examine safety and efficacy of Lapatinib in combination with a standard neoadjuvant chemotherapy including 5FU, Epirubicin, Cyclophosphamide and Paclitaxel. Tumor tissue will be obtained at 3 timepoints (optional 4th) to evaluate tumor response to treatment. 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?
Trastuzumab, Paclitaxel and FEC75
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
23 sitesUnited States
Study dates
Aug 2007to Aug 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Have signed an informed consent form (ICF) and a Patient Authorization Form (HIPAA).
  • Have histologically or cytologically confirmed ErbB2- (HER2/neu-) overexpressing invasive breast cancer (T2-4, N0-2).
  • ErbB2 overexpressing breast cancer, defined as one of the following definitions:
  • 3+ staining by immunohistochemistry (IHC),
  • a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus
  • a FISH ratio of more than 2.2.
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  • Have either measurable or evaluable disease.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 (Refer to Section 11.4).
  • Have LVEF within the institutional range of normal as measured by either echocardiogram (ECHO) or MUGA scans. The same modality must be used consistently throughout the study.
  • Be deemed able to tolerate 8 cycles of preoperative chemotherapy, including 4 cycles with an anthracycline (epirubicin).
  • Must be willing to undergo 2 mandatory core biopsies (4 passes each) after diagnosis to obtain tissue for biologic expression profiling. Any subject with clinically palpable residual disease may undergo an optional third biopsy to allow identification of presumed pathways of resistance to therapy. This information might be useful in providing the subject with options for other targeted therapies if definitive surgery confirms residual disease. Definitive local therapy with surgery and radiation therapy as indicated will be performed after completion of 12 weeks of paclitaxel-based chemotherapy.
  • Are able to swallow and retain oral medication (intact pill).
  • Are able to complete all screening assessments as outlined in the protocol.
  • Have adequate organ function as defined in Table 4:
  • Table 1 Baseline Laboratory Values
  • Hematologic:
  • ANC (absolute neutrophil count) >1.5 x 109/L hemoglobin >9 g/dL platelets >75 x 109/L
  • Hepatic:
  • albumin >2.5 g/dL serum bilirubin <1.25 x ULN AST / ALT <3 x ULN if no documented liver metastases AST / ALT <3 x ULN with documented liver metastases
  • Renal:
  • serum creatinine <2.0 mg/dL
  • OR - calculated creatinine clearance >40 mL/min
  • Are subjects aged >18 years with any menopausal status:
  • Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal)
  • Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
  • Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or Consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only) where not contraindicated for this subject population or per local practice.; or barrier methods, including diaphragm or condom with a spermicide.
  • Please note that breast cancer subjects on this trial cannot receive injectable levonorgestrel or injectable progestogen due to the potential for an adverse effect of anti-hormonal therapies on chemotherapy administered for breast cancer [Albain, 2002]. Progestogen may also affect the proliferative rate of endocrine-responsive tumors.

Who cannot join

  • Have received any prior chemotherapy.
  • Had prior therapy with an ErbB1 and/or ErbB2 inhibitor.
  • Are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication.
  • Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded.
  • Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety.
  • Have an active or uncontrolled infection.
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  • Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Have active cardiac disease, defined as one or more of the following:
  • History of uncontrolled or symptomatic angina History of arrhythmias requiring medications, or clinically significant Myocardial infarction <6 months from study entry Uncontrolled or symptomatic congestive heart failure Ejection fraction below the institutional normal limit Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Are pregnant or breastfeeding.
  • Have received concurrent treatment with an investigational agent or participate in another clinical trial.
  • Have received concurrent treatment with prohibited medications (refer to Section 5.8.2 for details on prohibited medications).
  • Have used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients.
  • Are receiving therapeutic anti-coagulation therapy (i.e. warfarin, heparin).

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • GSK Investigational Site

    Austin, Texas, 78731

  • GSK Investigational Site

    Beaumont, Texas, 77702-1449

  • GSK Investigational Site

    Bedford, Texas, 76022

  • GSK Investigational Site

    Dallas, Texas, 75231

  • GSK Investigational Site

    Dallas, Texas, 75246

  • GSK Investigational Site

    Dallas, Texas, 75320-2510

  • GSK Investigational Site

    Denver, Colorado, 80220

  • GSK Investigational Site

    El Paso, Texas, 79915

  • GSK Investigational Site

    Fountain Valley, California, 92708

  • GSK Investigational Site

    Henderson, Nevada, 89052

  • GSK Investigational Site

    Houston, Texas, 77024

  • GSK Investigational Site

    Hudson, Florida, 34667

  • GSK Investigational Site

    Indianapolis, Indiana, 46219

  • GSK Investigational Site

    Lewisville, Texas, 75067

  • GSK Investigational Site

    Los Angeles, California, 90057

  • GSK Investigational Site

    Miami, Florida, 33176

  • GSK Investigational Site

    Norfolk, Virginia, 23502

  • GSK Investigational Site

    Pembroke Pines, Florida, 33028

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19107

  • GSK Investigational Site

    Seattle, Washington, 98117

  • GSK Investigational Site

    Sugar Land, Texas, 77479

  • GSK Investigational Site

    Tyler, Texas, 75702

  • GSK Investigational Site

    Yakima, Washington, 98902

Other trials in United States

About this study

Official title: Phase II Randomized Trial of Neoadjuvant Trastuzumab and/or Lapatinib Plus Chemotherapy (Sequential FEC75 and Paclitaxel) in Women With ErbB2- (HER2/Neu-) Overexpressing Invasive Breast Cancer

This study will examine safety and efficacy of Lapatinib in combination with a standard neoadjuvant chemotherapy including 5FU, Epirubicin, Cyclophosphamide and Paclitaxel. Tumor tissue will be obtained at 3 timepoints (optional 4th) to evaluate tumor response to treatment.

Being tested
Trastuzumab, Paclitaxel, FEC75, Lapatinib
Keywords
ErbB2 Overexpressing, ErbB2 Positive, Lapatinib, Invasive 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

    4mg/kg IV loading dose followed by 2mg/kg IV weekly

  • PaclitaxelDrug

    80mg/m2 IV weekly for 4 (21 day) cycles

  • FEC75Drug

    5FU 500mg/m2 + Epirubicin 75 mg/m2 + cyclophosphamide 500 mg/m2 IV on day 1 of 4 (21 day) cycles

  • LapatinibDrug

    1250 mg oral daily dose in arm 2, 750 mg oral daily dose for FEC cycles and then 1000 mg oral daily dose during the Paclitaxel cycles in arm 3

Study groups in NCT00524303
Study groupRoleWhat they receive
Arm 1Active comparatorTrastuzumab alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles and Paclitaxel for 4 (21 day) cycles then continued trastuzumab until time of definitive surgery
Receives: Drug: Trastuzumab; Drug: Paclitaxel; Drug: FEC75
Arm 2ExperimentalLapatinib alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued lapatinib until time of definitive surgery
Receives: Drug: Paclitaxel; Drug: FEC75; Drug: Lapatinib
Arm 3ExperimentalTrastuzumab + Lapatinib for 2 weeks then added FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued trastuzumab + lapatinib until time of definitive surgery
Receives: Drug: Trastuzumab; Drug: Paclitaxel; Drug: FEC75; Drug: Lapatinib

What is being measured

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

  1. Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy

    A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.

    Measured: Week 26

Secondary outcomes (4)

  1. Percentage of Participants With Clinical Complete Response (cCR) at 26 Weeks or at End of Treatment (EOT) or Early Withdrawal

    cCR was defined as the percentage of participants achieving either a Complete Response (CR) or a Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

    Measured: Week 26 or EOT or Early withdrawal

  2. Percentage of Participants (Par.) With Disease-free Survival (DFS) at the End of 5 Years From Randomization

    Percentage is the Kaplan Meier estimate of DFS. DFS is time from randomization until disease recurrence (contralateral breast cancer; second primary cancer; progression during neo-adjuvant treatment; or death from any cause). Par. who experienced progression during treatment and were withdrawn were considered to have a DFS event at withdrawal.

    Measured: From first dose date until disease progression, assessed up to a maximum of 5 years

  3. Number of Participants With the Indicated Electrocardiogram (ECG) Status at Baseline and at EOT or Early Withdrawal

    12-lead ECGs were performed, and participants were classified as having normal ECG, abnormal- not clinically significant (NCS) ECG, and abnormal-clinically significant (CS) ECG per investigator opinion and reported result.

    Measured: Baseline and EOT (up to Week 26) or Early withdrawal

  4. Cumulative Number of Participants With at Least One Decrease of More Than or Equal to 20% in Left Ventricular Ejection Fraction (LVEF) at the Indicated Time Points Compared to LVEF at Baseline

    LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction and is used to determine cardiac function. LVEF was measured by performing echocardiogram (ECHO). If ECHO could not be performed or if the investigator believed that it was not conclusive to evaluate LVEF, then a multigated acquisition (MUGA) scan was performed.

    Measured: Weeks 3, 9, and 15; EOT or early withdrawal; and 3- and 6-month survival follow-up after last chemotherapy course

Timeline

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

  1. First posted3 Sep 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionOct 2010
  4. Study completionAug 2015

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
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00524303
Sponsor's protocol ID
LPT109096
Status last verified
Mar 2016
First submitted
31 Aug 2007
Last updated
11 Nov 2016
Data monitoring committee
No

Publications

  • O'Shea J, Cremona M, Morgan C, Milewska M, Holmes F, Espina V, Liotta L, O'Shaughnessy J, Toomey S, Madden SF, Carr A, Elster N, Hennessy BT, Eustace AJ. A preclinical evaluation of the MEK inhibitor refametinib in HER2-positive breast cancer cell lines including those with acquired resistance to trastuzumab or lapatinib. Oncotarget. 2017 Jul 22;8(49):85120-85135. doi: 10.18632/oncotarget.19461. eCollection 2017 Oct 17.

    PubMed 29156708

  • Holmes FA, Espina V, Liotta LA, Nagarwala YM, Danso M, McIntyre KJ, Osborne CR, Anderson T, Krekow L, Blum JL, Pippen J, Florance A, Mahoney J, O'Shaughnessy JA. Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling. BMC Res Notes. 2013 Dec 5;6:507. doi: 10.1186/1756-0500-6-507.

    PubMed 24304724

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab, Paclitaxel and FEC75 in people with Neoplasms, Breast, run by GlaxoSmithKline at 23 sites in United States.

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 27 inclusion and 15 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 11 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. 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?

Yes. Results are posted in the registry (first posted 11 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy (time frame: Week 26). 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 NCT00524303, which also lists 2 linked publications.

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 11 Nov 2016.

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