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Phase Ib Study of Preoperative Chemotherapy With Paclitaxel, Gemcitabine, and Lapatinib (Tykerb®) (PGT) in Patients With HER2 Positive Operable Breast Cancer

Phase 1
18 Years
Not Enrolling
Breast Cancer

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Trial Information

Phase Ib Study of Preoperative Chemotherapy With Paclitaxel, Gemcitabine, and Lapatinib (Tykerb®) (PGT) in Patients With HER2 Positive Operable Breast Cancer

Unlike adjuvant chemotherapy, primary (preoperative) chemotherapy will shrink tumor and
allow some patients to become candidates for conservative surgery and avoid mastectomy. It
also is an in vivo chemosensitivity test and the result is a predictive marker for clinical
outcomes. Paclitaxel is a highly active antitumor agent that promotes microtubule assembly
by binding to tubulin and inhibiting depolymerization. Paclitaxel has been shown to be an
effective agent in the treatment of breast cancer. Gemcitabine is a cytosine arabinoside
prodrug analog and shows response rates of 15% to 46% as a single agent with very low
toxicity. The combination of gemcitabine and paclitaxel is valuable because of the different
mechanisms of action of each drug and their non-overlapping toxicities. Phase II studies of
paclitaxel plus gemcitabine in anthracycline-pretreated metastatic breast cancer showed good
tolerance and encouraging response rates (40%-55%). Paclitaxel plus gemcitabine combination
showed overall survival benefit compared to paclitaxel alone in patients with metastatic
breast cancer in an interim overall survival report. A phase II study with preoperative
paclitaxel and gemcitabine in stage II/III showed 18 % pCR rate at NCC (ASCO 2007 abstract
#11080) In HER2 positive breast cancer, HER2 targeted therapies with trastuzumab and
lapatinib have shown much improved clinical response in palliative setting. It also showed
that adding trastuzumab to sequential paclitaxel and FEC chemotherapy significantly
increased pCR (25% vs 66.7%) in preoperative setting for HER2 positive disease. Recently,
paclitaxel, gemcitabine, and trastuzumab combination (PGH) for 6 cycles in patients with
HER2 positive and node positive operable breast cancer observed a strikingly high pCR rate
in both tumor and LN in an interim analysis of multicenter phase II preoperative study in
Korea (28 of 47 (61%)). Lapatinib (Tykerb®), a dual tyrosine kinase inhibitor of ErbB1 and
HER2 signaling pathways and it has shown to inhibit the growth of HER2 overexpressing breast
cancer cells that do not respond to trastuzumab after long-term conditioning. We will
examine the hypothesis that paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT)
combination could improve the pathological complete response rate of HER2 positive breast
cancer when applied as a preoperative chemotherapy.

Inclusion Criteria:

- Histologically confirmed and newly diagnosed operable breast cancer

- Documented HER2 positive disease : 3+ overexpression by IHC or HER2 gene
amplification by FISH

- ECOG performance status 0-2

- Age ≥ 18 years

- Clinical stage II or III operable breast cancer

- Axillary node positivity determined by cytology

- No prior hormonal, chemotherapy, or radiotherapy is allowed

- No breast operation other than biopsy to make diagnosis is allowed

- Negative urine pregnancy test within 7 days prior to registration in premenopausal

- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet
≥100,000/mm3, hemoglobin ≥10g/mm3

- Adequate hepatic function: total bilirubin ≤1.5mg/dL, AST/ALT ≤2 x UNL, alkaline
phosphatase ≤2 x UNL

- Adequate renal function: Serum creatinine ≤1.5mg/dL

- Adequate cardiac function:

1. Normal or nonspecific EKG taken within 1 month of enrollment

2. LVEF ≥50% by MUGA or echocardiogram taken within 4 weeks of enrollment

- Ability to understand and comply with protocol during study period

- Patients should sign a written informed consent before study entry

Exclusion Criteria:

- Pregnant or lactating women

- Patients who received hormonal, chemotherapy or radiotherapy for breast cancer

- Patients with bilateral breast cancer

- Patients who underwent surgery for breast cancer

- Patients with node-negative stage IIA (T2N0) breast cancer

- Patients who have history of cancer other than in situ uterine cervix cancer or
nonmelanotic skin cancer

- 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 GI disease (e.g., Crohn's disease, ulcerative

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the recommended dose of the combination of paclitaxel, gemcitabine, and lapatinib (Tykerb®) (PGT) as preoperative chemotherapy in patients with HER2 positive operable breast cancer

Outcome Time Frame:

two years

Safety Issue:


Principal Investigator

Jungsil Ro, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cencer Center, Korea


Korea: Food and Drug Administration

Study ID:




Start Date:

March 2009

Completion Date:

October 2011

Related Keywords:

  • Breast Cancer
  • Patients with HER2 Positive Operable Breast Cancer
  • Breast Neoplasms