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Phase II Study of a Novel Capecitabine Dosing Schedule in Combination With Lapatinib, Based on the Norton-Simon Mathematical Method in Patients With HER2 Overexpressed/Amplified, Trastuzumab (Herceptin) -Refractory, Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase II Study of a Novel Capecitabine Dosing Schedule in Combination With Lapatinib, Based on the Norton-Simon Mathematical Method in Patients With HER2 Overexpressed/Amplified, Trastuzumab (Herceptin) -Refractory, Metastatic Breast Cancer

Inclusion Criteria:

- Patients with a diagnosis of invasive adenocarcinoma of the breast confirmed by
histology or cytology at MSKCC.

- Clinical evidence of metastatic breast cancer.

- HER2 overexpression and/or amplification as determined by immunohistochemistry (3+)
or FISH (≥2.0).

- Progressive disease following treatment with trastuzumab for metastatic breast cancer
or as adjuvant therapy (either single-agent or combination therapy)

- Prior therapy inclusion:

- No more than two prior chemotherapy regimens allowed for advanced stage disease

- No prior fluoropyrimidine in the metastatic setting. Adjuvant fluoropyrimidine
is permitted if >6 months prior to treatment on study.

- No restriction for prior hormonal therapy. No concurrent use of endocrine
therapy is permitted.

- No more than 450mg/m2 cumulative dose of prior doxorubicin

- At least 3 weeks since prior chemotherapy or radiation therapy

- Age ≥ or = to 18. Because no dosing or adverse event data are currently available on
the use of lapatinib in patients <18 years of age, children are excluded from this

- Patients must be willing to discontinue sex hormonal therapy e.g., birth control
pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of
childbearing potential must be willing to consent to using effective contraception
while on treatment and for a reasonable period thereafter.

- Negative HCG pregnancy test for premenopausal women of reproductive capacity and for
women less than 12 months after the menopause.

- Asymptomatic, central nervous system metastases are permitted if patients remain
clinically stable after discontinuation of corticosteroids and anticonvulsants.

- ECOG performance status < or = to 2

- Life expectancy of greater than 12 weeks

Patients must have normal organ and marrow function as defined below:

- leukocytes ≥ or = to 3,000/μL

- absolute neutrophil count ≥ or = 1,500/μL

- platelets ≥ or = 100,000/μL

- total bilirubin within normal institutional limits AST (SGOT)/ALT(SGPT) ≤ or = 2.5x
institutional upper limit of normal serum creatinine within normal institutional

- Cardiac ejection fraction at or above the lower limit of normal of 50% as
measured by multigated radionuclide angiography (MUGA) scan. If LVEF is greater
than 70%, and ECHO should be performed as well. Baseline and on treatment scans
should be performed using the same modality and preferably at the same

- Ability to understand and the willingness to sign a written informed. consent

- Able to swallow and retain oral medication.

Exclusion Criteria:

- Patients may not be receiving any concurrent anticancer therapy or investigational
agents with the intention of treating breast cancer.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lapatinib or capecitabine.

- Known DPD deficiency.

- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial
infarction within 6 months of study entry, uncontrolled cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study

- Pregnant women are excluded from this study because lapatinib is member of the 4-
anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with lapatinib,
breastfeeding should be discontinued if the mother is treated with lapatinib.

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with lapatinib.
Appropriate studies will be undertaken in patients receiving combination
anti-retroviral therapy when indicated.

- 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

- Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors:

- Medications that inhibit or induce CYP3A4 are prohibited. Eligibility of patients
receiving medications or substances known to affect, or with the potential to affect
the activity or pharmacokinetics of lapatinib will be determined following review of
their use by the Principal Investigator.

- Renal function as measured by creatinine clearance < 30ml/min

- Patients are permitted to participate in other non-therapeutic clinical trials while
receiving treatment on this study (ie, experimental imaging, minor procedures
necessary for tissue acquisition on study)

Type of Study:


Study Design:

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

Outcome Measure:

Estimate efficacy of capecitabine 7/7 in combination with lapatinib in patients with HER2 overexpressed/amplified, trastuzumab-refractory, metastatic breast cancer as determined by overall response rate (complete response (CR) + partial response (PR))

Outcome Time Frame:

conclusion of the study

Safety Issue:


Principal Investigator

Tiffany Traina, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

July 2008

Completion Date:

July 2013

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
Memorial Sloan-Kettering Cancer Center at Commack Commack, New York  11725
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Rockville Centre, New York  11570
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Sleepy Hollow, New York  10591
Memorial Sloan-Kettering at Basking Ridge Basking Ridge, New Jersey  07920