Randomized Discontinuation Study of Lapatinib Versus Placebo in Subjects With Documented Tumor Progression After Chemotherapy, or Where no Approved Therapy Exists
Condition: Cancer
Intervention: Oral lapatinib tablets or placebo tablets
Intervention description: Subjects administered open label lapatinib, 1500 mg to be taken orally once a day, for 12 weeks. After 12 weeks, subjects with a partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) will continue to receive open label lapatinib (1500 mg/day orally) until disease progression. Subjects who maintain stable disease will be randomized in a 1:1 ratio to enter stage 2 of the study and receive double blind therapy of either lapatinib 1500 mg/day orally or placebo. Subjects who progress on placebo will have the option to receive lapatinib 1500 mg/day orally until further progression. Those who progress on lapatinib will be withdrawn from the study.
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer; Bladder Cancer; ErbB2 positive; Lapatinib; Gastric/Esophageal Cancer; Uterine Serous Papillary Cancer

Summary:

      This study will examine the efficacy and safety of lapatinib in patients with ErbB2 positive
      ovarian, gastric/esophageal adenocarcinoma, uterine serous papillary, or bladder cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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)
             assay.

          -  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
             therapy.

          -  Have a gastrointestinal tract intact enough to swallow and assure absorption of the
             drug.

          -  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
             treatment.

          -  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:

        Hematologic:

        absolute neutrophil count >1.5 x 109/L hemoglobin >9 g/dL platelets >75 x 109/L

        Hepatic:

        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
        metastases

        Renal:

        serum creatinine <2.0 mg/dL

          -  OR - calculated creatinine clearance1 >40 mL/min

        Exclusion Criteria:

          -  Have New York Heart Association Class III or IV, cardiac disease, myocardial
             infarction within past 6 months, unstable arrhythmia or evidence of ischemia on
             electrocardiogram.

          -  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
             ulcerative colitis.

          -  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.