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An Open-Label Phase I Study of Fixed Dose Lapatinib in Combination With an Escalating Dose of Epirubicin in Metastatic Breast Cancer

Phase 1
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

An Open-Label Phase I Study of Fixed Dose Lapatinib in Combination With an Escalating Dose of Epirubicin in Metastatic Breast Cancer



- To assess the safety and tolerability of fixed-dose lapatinib ditosylate in combination
with epirubicin hydrochloride in patients with metastatic breast cancer.

- To determine the optimally-tolerated regimen in these patients.


- To determine the clinical efficacy of this regimen in these patients.

- To analyze pharmacokinetic data of this regimen.

- To determine biomarkers that correlate with clinical benefit or response to lapatinib
ditosylate in these patients.


- To identify tumor-derived or blood-derived biomarkers that correlate with or are
predictive of clinical response or benefit to lapatinib ditosylate in these patients.

- To determine the levels of IGF-IR and phosphorylated IGF-IR in tumor tissue.

- To determine the expression pattern of the proteins associated with drug resistance
that may be clinically active in these patients.

OUTLINE: This is a multicenter, dose-escalation study of epirubicin hydrochloride.

Patients receive oral lapatinib ditosylate followed by epirubicin hydrochloride IV over
15-30 minutes on day 1. Treatment repeats every 3 weeks for up to 7 courses in the absence
of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic analysis via liquid
chromatography-mass spectometry (LC-MS).

After completion of study therapy, patients are followed at 28 days and then every 3 months

Inclusion Criteria


- Confirmed diagnosis of breast cancer

- Metastatic disease

- No de novo metastasis

- Hormone receptor status not specified


- ECOG performance status 0-1

- Life expectancy > 3 months

- Menopausal status not specified

- ANC ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin ≥ 9 g/dL

- Creatinine clearance ≥ 50 mL/min

- AST/ALT < 3 times upper limit of the normal (ULN)

- Total bilirubin normal (unless documented history of congenital hypobilirubinemia)

- LVEF normal by ECHO or MUGA scan

- Not pregnant or breastfeeding

- Negative pregnancy test

- Fertile patients must use effective contraception from the time of their negative
pregnancy test before treatment, during treatment, and 28 days following treatment

- Able to swallow and retain oral medication

- History of other malignancies (e.g., cervical carcinoma in situ, melanoma in situ, or
basal cell or squamous cell carcinoma of the skin) allowed provided patient has been
treated and disease free ≥ 5 years and deemed by the investigator to be at low risk
for recurrence

- No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to lapatinib ditosylate or excipients

- No malabsorption syndrome, disease significantly affecting gastrointestinal function,
resection of the stomach or small bowel, or ulcerative colitis

- No active or uncontrolled infection

- No known history of uncontrolled or symptomatic angina, arrhythmias, congestive heart
failure, or other cardiac disorders

- No history of prolonged QT interval

- No active hepatic or biliary disease (except for Gilbert's syndrome, asymptomatic
gallstones, liver metastases or stable chronic liver disease per investigator

- No concurrent disease or condition that would render the patient inappropriate for
study participation, or serious medical disorder that would interfere with the
patient's safety

- No dementia, altered mental status, or psychiatric condition that would prohibit the
understanding or rendering of informed consent


- Prior radiotherapy for treatment of primary tumor allowed

- Prior non-anthracycline based regimens in neoadjuvant, adjuvant, or metastatic
setting allowed

- Prior adjuvant Herceptin® or ErbB inhibitors allowed provided disease progression was
> 6 months after completion of treatment

- More than 3 months since prior Herceptin®, ErbB1, or ErbB2

- No prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or
anthracenedione-containing regimens

- More than 3 weeks since prior and no concurrent medications that would prolong QT

- More than 1 month or 5 half-lives (whichever is longer) since prior, no concurrent
investigational drugs

- No unresolved or unstable, serious toxicity from prior investigational drug and/or
cancer treatment

- At least 3 weeks since prior and no concurrent prohibited medications (i.e., CYP3A4
inducers or inhibitors)

- No concurrent non-study anticancer therapy (i.e., chemotherapy, immunotherapy, or
biologic therapy)

- No concurrent participation in another clinical trial

- No concurrent grapefruit or grapefruit juice

- Concurrent bisphosphonates allowed

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride

Safety Issue:


Principal Investigator

John Crown, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

St. Vincent's University Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

October 2007

Completion Date:

March 2012

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms