An Open-Label Expanded Access Study of Lapatinib and Capecitabine Therapy in Subjects with ErbB2 Over-expressing Locally Advanced or Metastatic Breast Cancer

Study Objective

Primary

To offer pre-approval drug access to Lapatinib, in combination with Capecitabine, in order to provide potential clinical benefit to subject with ErbB2 overexpressing breast cancer, who have previously received anthracyclines, taxanes and trastuzumab, and who are not eligible for another ongoing Lapatinib clinical trial.

Secondary

To evaluate the serious adverse events (SAEs) associated with this combination therapy in this population of patients with locally advanced or metastatic breast cancer.

Participation conditions

Inclusion criteria

• Signed informed consent.
• Subjects must not be eligible for another ongoing Lapatinib clinical trial.
• Subjects may have received prior Lapatinib therapy in another clinical trial. Previous Capecitabine therapy (as previous agent or a non-Lapatinib-containing regimen) is also permitted.
• Prior treatment with hormonal therapy is allowed.
• Subjects must have advanced or metastatic breast cancer with progression (as assessed by modified RECIST) after prior therapy, which must include all of the following: prior treatment with an anthracycline, a taxane, and trastuzumab alone or in combination with other therapy. Trastuzumab must have been administered in the adjuvant, or locally advanced or metastatic setting.
• Subjects must have tumors that overexpress ErbB2 defined as +3 by IHC or FISH positive for ErbB2 gene amplification. The status of ErbB2 expression must be documented prior to study entry.
• Subjects (male or female) must be >18 years of age.
• Subjects must have an ECOG Performance Status of 0 to 2.
• Life expectancy >8 weeks.
• Subjects must have recovered or stabilized sufficiently from side effects associated with prior treatments before beginning treatment with Lapatinib and Capecitabine.
• Subjects with central nervous system (CNS) metastases are eligible, providing treatment with prohibited medications, listed under Section 13.4 Appendix 4, are not required.
• Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram (ECHO). Measurements with MUGA scans are allowed if echocardiograms cannot be performed. Subjects with symptomatic angina, arrhythmias, or congestive heart failure are not eligible
• Subjects must not be taking any medication listed in the 'Prohibited Medications' listing (Section 13.4).
• Able to swallow and retain oral medications.
• Subjects must complete all screening assessments as outlined in the protocol.
• Subjects must have adequate hematologic, hepatic and renal function, as defined below:
   

Exclusion criteria

• Pregnant or lactating females at anytime during the study.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are also excluded.
• Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety.
• Unresolved or unstable serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
• Uncontrolled infection.
• Dementia, altered mental status or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• 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, with the exception of asymptomatic atrial fibrillation requiring anticoagulation.
  • 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.
     
• Subjects receiving concurrent chemotherapy {other than Capecitabine), radiation therapy, immunotherapy, biologic therapy (including a ErbB1 and/or ErbB2 inhibitor) or hormonal therapy for treatment of their cancer. Hormone therapy for ovarian suppression is allowed. Concurrent treatment with bisphosphonates is allowed.
• History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to Lapatinib or to any excipients.
• History of allergic reactions attributed to compounds of similar chemical composition to Capecitabine, fluorouracil or to any excipients.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Subjects meeting any of the following criteria must not be enrolled in the study: Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

Oncologists at Centre Hospitalier de Luxembourg