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HER2-positive Breast CancerPhase 2NCT01688609

Lapatinib Ditosylate, Trastuzumab, Paclitaxel, and Surgery in Treating Patients With Breast Cancer

A Phase 2 study testing lapatinib ditosylate, paclitaxel and trastuzumab in people with HER2-positive Breast Cancer and Stage II Breast Cancer, run by National Cancer Institute (NCI) at 3 sites in 2 countries.

Completed

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

Official record
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Trial summary

This phase II trial studies how well giving lapatinib ditosylate together with trastuzumab, paclitaxel, and surgery works in treating patients with breast cancer. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 20 years and older, women only
What is being tested?
lapatinib ditosylate, paclitaxel and trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
3 sitesin 2 countries
Study dates
Jul 2012to 15 Aug 2016
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 20 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed primary invasive breast cancer
  • Primary tumor is larger than 2 cm in diameter (T2) as measured by caliper or ultrasound
  • Overexpression and/or amplification of HER2 is confirmed by immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) + when IHC 2+
  • Patients have not received prior therapies for breast cancer
  • Patients have Karnofsky >= 70%
  • Leukocytes >= 3,000/mcL
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  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9.0 g/dL
  • Platelets >= 75,000/mcL
  • Total bilirubin =< 1.5 times institutional upper limit of normal
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase[SGPT]) =< 2.5 times institutional ULN
  • Creatinine =< 1.5 times institutional upper limit of normal (ULN)
  • Patients must have left ventricular ejection fraction (LVEF) >= 50% by multi-gated acquisition (MUGA) or echocardiography
  • Patients must be able to take oral medications (i.e., no uncontrolled vomiting, inability to swallow, or diagnosis of chronic malabsorption)
  • Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation as well as for at least 6 months after the last dose of trastuzumab
  • Ability to understand and willingness not only for treatment but also for undergoing serial biopsies and sign a written informed consent document
  • Only Japanese women are eligible for the trial

Who cannot join

  • Patients who have had chemotherapy or radiotherapy
  • Patients who are receiving any other investigational agents
  • Patients have distal metastasis (stage IV disease)
  • Patients with previous (within 10 years) or current history of malignant neoplasm except for curatively treated basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in study
  • Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) are ineligible
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  • Patients who have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women
  • Patients who have family or personal history of congenital long or short QT syndrome, Brugada syndrome, QT/QTc prolongation, or torsade de pointes
  • Patients who have chronic gastrointestinal disease presenting with diarrhea (inflammatory bowel disease, malabsorption, or >= grade 2 diarrhea of any etiology at baseline)
  • Patients who have neuropathy >= grade 2 of any cause
  • Patients are diagnosed with inflammatory breast cancer or bilateral breast cancer

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Japan2 sites

  • Saint Luke's International Hospital

    Chūōku, Toyko, 104-8560

  • Keio University

    Shinjuku-ku, Tokyo, 160-8582

Other trials in Japan

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Lapatinib and Trastuzumab Followed by Concurrent Lapatinib, Trastuzumab, and Paclitaxel Followed by Surgery for Primary HER2-positive (HER2+) Breast Cancer

This phase II trial studies how well giving lapatinib ditosylate together with trastuzumab, paclitaxel, and surgery works in treating patients with breast cancer. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the changes in cancer stem cell (CSC) markers; % CD44 variant (CD44v)-positive tumor cells and aldehyde dehydrogenase-1 (ALDH1) positivity before and after study drug exposure and after concurrent preoperative chemotherapy.

II. To determine the pathological complete response (pCR) rate produced by lapatinib (lapatinib ditosylate) + trastuzumab followed by concurrent preoperative lapatinib, trastuzumab, and paclitaxel chemotherapy for operable human epidermal growth factor receptor 2-positive (HER2+) breast cancer.

SECONDARY OBJECTIVES:

  1. To determine the cellular response rate produced by study drug exposure and/or concurrent preoperative chemotherapy.

II. To determine cutoff values of baseline ratios of phosphorylated HER2 (pHER2)/HER2, phosphorylated epidermal growth factor receptor (EGFR) (pEGFR)/EGFR, phosphorylated ERK (pERK)/ERK and phosphorylated protein kinase B (pAkt)/Akt that are associated with pCR.

III. To assess the safety and tolerability of study therapy in Japanese women.

OUTLINE:

Drug exposure: Patients receive lapatinib ditosylate orally (PO) once daily (QD) and trastuzumab intravenously (IV) over 30-90 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity.

Preoperative therapy: Patients receive lapatinib ditosylate PO QD, trastuzumab IV over 30 minutes once weekly, and paclitaxel IV over 90 minutes once weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo lumpectomy* or mastectomy*.

After completion of study treatment, patients are followed up for 12 weeks.

NOTE: * Patients considered to be candidates for breast-conservation therapy (BCT) are offered lumpectomy. Patients who are not considered to be candidates for BCT or who do not desire BCT undergo total mastectomy.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • lapatinib ditosylateDrug

    Also called GSK572016, GW-572016, GW2016, Lapatinib

    Given PO

  • paclitaxelDrug

    Also called Anzatax, Asotax, TAX, Taxol

    Given IV

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, MOAB HER2

    Given IV

  • therapeutic conventional surgeryProcedure or surgery

    Undergo lumpectomy or mastectomy

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01688609
Study groupRoleWhat they receive
Treatment (lapatinib, trastuzumab, paclitaxel, surgery)ExperimentalDrug exposure: Patients receive lapatinib ditosylate PO QD and trastuzumab IV over 30-90 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Preoperative therapy: Patients receive lapatinib ditosylate PO QD, trastuzumab IV over 30 minutes once weekly, and paclitaxel IV over 90 minutes once weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo lumpectomy or mastectomy.
Receives: Drug: lapatinib ditosylate; Drug: paclitaxel; Biological: trastuzumab; Procedure: therapeutic conventional surgery; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks

    For biomarkers ALDH1 and CD44v, the change in the proportions of CD44v-positive (CD44v+) tumor cells and ALDH1-positive (ALDH1+) tumor cells in tumor tissue from baseline to 6 weeks and 18 weeks time points were determined for each patient. For biomarker change, changes in the binary biomarkers between time points were assessed using McNemar's test in all patients and separately in patients with and without pCR.

    Measured: From baseline to 18 weeks

  2. Number of Participants With Pathological Complete Response (pCR)

    The point estimate of the pCR rate will be calculated for all patients. pCR is defined as the abscence of invasive cancer in the breast and regional lymph nodes following neoadjuvant chemotherapy.

    Measured: Up to 12 weeks

Secondary outcomes (3)

  1. Cellular Response Rate, Defined as Patients With an Epithelial Phenotype Having Eradication of CTCs; Patients With a Mesenchymal Phenotype Having Eradication of Tumor Cells; Patients With a Mesenchymal Phenotype Converting to an Epithelial Phenotype

    Cellular response will be documented and calculated for rate in all patients.

    Measured: Up to 18 weeks

  2. EGFR-mutation Status of Tumors and Changes in the Ratio of Phosphorylated to Nonphosphorylated HER2, EGFR, ERK, Akt, and the Ki67 and TUNEL Indices Before and After Treatment

    The EGFR mutation status will be a binary variable (yes vs. no), and the phosphorylation status of HER2 and EGFR will be a ratio variable (0-100%). The CART method to identify cut-off points for the phosphorylation ratio of molecules of interest will be used, such that ratios above the cut-off point will be considered "high phosphorylation" and ratios below the cut-off point will be considered "low phosphorylation."

    Measured: From baseline to 24 weeks

  3. Number of Participants With Treatment-Related Toxicities

    Measured: Up to 12 weeks after completion of study treatment

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 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionDec 2013
  4. Study completion15 Aug 2016

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01688609
Sponsor's protocol ID
NCI-2012-01970
Other IDs
NCI-2012-01970, CDR0000734375, ACE-001, 9020
Status last verified
Aug 2017
First submitted
16 Sep 2012
Last updated
11 Sep 2017

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lapatinib ditosylate, paclitaxel and trastuzumab in people with HER2-positive Breast Cancer and Stage II Breast Cancer, run by National Cancer Institute (NCI) at 3 sites in 2 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 17 inclusion and 12 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 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan, 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 Sep 2017). 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?

Expression of ALDH1 and CD44v Change in the Binary Biomarkers From Baseline to 6 Weeks and 18 Weeks (time frame: From baseline to 18 weeks). The study lists 2 primary outcomes in all. 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 NCT01688609.

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 Sep 2017.

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