A Phase II, Placebo Controlled, Double-Blind, Randomized, Discontinuation Study of Lapatinib Administered Orally to Subjects With ErbB2 Positive Ovarian, Gastric/Esophageal Adenocarcinoma, Uterine Serous Papillary, or Bladder Cancer
- Signed written informed consent.
- Age >= 18 years old.
- Life expectancy of at least 12 weeks.
- Have histologically confirmed ovarian, gastric/esophageal adenocarcinoma, uterine
serous papillary, or bladder cancer.
- Have ErbB2-positive cancer as determined by Fluorescence In Situ Hybridization (FISH)
- Have documented tumor progression after receiving all standard/approved
chemotherapies per National Comprehensive Cancer Network (NCCN) guidelines (V1) for
their specific cancer and no approved therapy exists.
- Have one or more tumors measurable by medical imaging and assessed using the Response
Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Have archived tumor tissue available for biomarker analysis.
- Have a negative serum pregnancy test if female of childbearing potential.
- Any chemotherapy, major surgery, or irradiation must have been completed at least 3
weeks prior to receiving study drug (6 weeks for mitomycin-C or nitrosourea) and
subject must have recovered from all toxicities incurred as a result of previous
- Have a gastrointestinal tract intact enough to swallow and assure absorption of the
- Women of childbearing potential must have a negative serum pregnancy test at
screening and must use an approved contraceptive method, if appropriate (for example,
intrauterine device, birth control pills, or barrier device) beginning 2 weeks before
the first dose of investigational product and for 28 days after the final dose of
investigational product. Males able to father a child must practice adequate methods
of birth control or practice complete abstinence from intercourse from the first dose
of investigational treatment until one week after the final dose of investigational
- Have a cardiac ejection fraction within institutional range of normal as measured by
either echocardiogram or multigated acquisition scans. The same method of cardiac
evaluation must be used consistently throughout the study.
- Subjects must have adequate organ function:
absolute neutrophil count >1.5 x 109/L hemoglobin >9 g/dL platelets >75 x 109/L
albumin >2.5 g/dL serum bilirubin <1.25 x upper limit of normal aspartate
aminotransferase/alanine aminotransferase <3 x ULN if no documented liver metastases
aspartate aminotransferase/alanine aminotransferase <5 x ULN with documented liver
serum creatinine <2.0 mg/dL
- OR - calculated creatinine clearance1 >40 mL/min
- Have New York Heart Association Class III or IV, cardiac disease, myocardial
infarction within past 6 months, unstable arrhythmia or evidence of ischemia on
- Subjects who have had chemotherapy or radiotherapy within 3 weeks prior to entering
the study or who have unresolved or unstable, serious toxicity from prior
administration of another investigational drug and/or of prior cancer treatment.
- Concurrent treatment with an investigational agent or participation in another
treatment clinical trial.
- Prior lapatinib therapy.
- ECOG Performance Status 2 or greater.
- Subjects receiving concurrent chemotherapy, radiation therapy, immunotherapy,
biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for
treatment of their cancer. Concurrent treatment with bisphosphonates is allowed.
- History of allergic reactions attributed to compounds of similar chemical composition
(quinazolines) to lapatinib.
- Concurrent treatment with prohibited medications.
- Malabsorption syndrome, resection of the small bowel or active, uncontrolled
- Concurrent disease or condition that would make the subject inappropriate for study
participation or any serious medical or psychiatric disorder that would interfere
with the subject's safety.
- Uncontrolled infection.
- Pregnant or lactating females.