Please select the eligibility criteria that correspond to the clinical trial below.
Title: 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
Brief 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.


Options:
A: Inclusion Criteria:

* Histologically or pathologically confirmed diagnosis of epithelial carcinoma of the ovary or primary peritoneal carcinoma.
* Relapsed after prior therapy with taxane and platinum-based therapy, within 6 months of completing, or had a best response of stable disease during no more than two prior chemotherapy treatments with a platinum (either cisplatin or carboplatin) and a taxane (paclitaxel or docetaxel). These agents may have been administered concurrently or sequentially. Besides the primary chemotherapy, two additional chemotherapy regimens are allowed. Hormonal therapy is allowed and will not be counted as a chemotherapy regimen.
* Up to one year of consolidation treatment with intraperitoneal and intravenous administered chemotherapy drugs to consolidate a clinical complete remission is allowed.
* Patients must have elevated CA-125 or measurable disease.
* For patients who do not have RECIST measurable disease, an elevated CA-125 (greater than two times the institutional upper limit of normal) will be required for enrollment.
* Debulking surgery for relapsed disease is allowed but must be completed at least 28 days prior to the first day of study therapy. Patient must have recovered from all side effects of surgery including a completely healed surgical incision.
* Patient must have a Zubrod performance status of 0-1.
* Patient must have adequate hepatic function as defined by:

  * a serum bilirubin ≤1.5 x the institutional upper limit of normal (IULN),
  * SGOT or SGPT ≤2.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy
* Patient must have an adequate renal function as defined by:

  * a serum creatinine ≤1.5 x the institutional upper limit of normal obtained within 14 days prior to start of therapy and a urine protein:creatinine (UPC) ratio of ≤ 1.0.
* Patients must be able to take oral medications
* Patients may not have ongoing problems with bowel obstruction or short bowel syndrome characterized by grade 2 or greater diarrhea or malabsorptive disorders.
* Patients must have the following hematological criteria:

  * Hemoglobin of \>10gm/dL,
  * White blood cell count \>2500,
  * Platelets \>80,000
* Patients must be ≥ 18 years of age.

Exclusion Criteria:

* Subjects with mixed mullerian tumors and borderline ovarian tumors are excluded. Patients with a history of borderline ovarian tumors that have evolved into higher grade tumors will be eligible.
* The patient must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to start of therapy and must have recovered from toxicities of prior therapy to grade 1 or less with the exception of alopecia.
* Patient must not be pregnant or nursing because bevacizumab or erlotinib maybe harmful to the developing fetus and newborn. Women of reproductive potential must have a negative serum pregnancy test within 7 days prior to study consent. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
* Patients should not have psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol.
* Except for cancer-related abnormalities, patients should not have unstable or preexisting major medical conditions.
* Patients should not have any medical life-threatening complications of their malignancies
* Patients should not have a known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV)
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
* Baseline blood pressure of \< or equal to 150/100 mmHg. Patients with a blood pressure reading above this level should be initiated on anti-hypertensive therapy and may be considered for protocol treatment when their blood pressure is adequately controlled.
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* History of myocardial infarction, cerebrovascular accident, transient ischemic attack, or unstable angina within 6 months
* Clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Presence of central nervous system or brain metastases
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
* Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
* Pregnant (positive pregnancy test) or lactating
* Urine protein:creatinine ratio \> equal to 1.0 at screening
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
* Serious, non-healing wound, ulcer, or bone fracture
* Diagnosis of any other malignancy except non-melanomatous skin cancer in the past 5 years.
* Inability to comply with study and/or follow-up procedures
B: DISEASE CHARACTERISTICS:

* Histologically proven stage IIIC or IV ovarian epithelial carcinoma, peritoneal carcinoma, or fallopian tube carcinoma

  * If biopsy is not available, evidence of adenocarcinoma by fine needle aspiration allowed if all of the following are true:

    * Presence of pelvic ovarian mass
    * Omental cake or other metastasis larger than 2 cm in the upper abdomen and/or regional lymph node metastasis
    * CA 125/carcinoembryonic antigen ratio greater than 25 (if ratio less than 25, barium enema or colonoscopy AND gastroscopy or radiological examination of the stomach must be negative for primary tumor)
    * Normal mammography (if CA 125/carcinoembryonic antigen ratio less than 25)
* Tumor greater than 2 cm, excluding ovaries, on laparoscopy or CT scan
* No brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

* Not specified

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 3,000/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Bilirubin less than 1.25 times upper limit of normal (ULN)

Renal:

* Creatinine less than 1.25 times ULN

Other:

* No other serious disabling diseases contraindicating primary cytoreductive surgery or primary platin-based chemotherapy
* No other prior primary malignancies except carcinoma in situ of the cervix or basal cell carcinoma of the skin
* No psychological, familial, sociological, or geographical condition potentially preventing protocol compliance or follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* No other prior procedures except diagnostic biopsy by laparotomy or laparoscopy
C: 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.
D: Inclusion Criteria:

* Histopathologically documented invasive epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory to platinum-based chemotherapy or with partially platinum sensitive disease.
* Planned therapy with pegylated liposomal doxorubicin 50 mg/m² for recurrent platinum-refractory ovarian cancer.
* Patients with a progression-free-interval of 6 to 12 months after platinum-based chemotherapy are only eligible if a further course of platinum-based combination chemotherapy is not possible as judged by the investigator(s).
* Patients must have received at least one previous platinum- and taxane-based chemotherapy regimen.

Exclusion Criteria:

* Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days
* Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes or induce CYP3A4 function
* Treatment with mouse-antibodies in patients with evaluable disease and CA-125 progressive disease in the last 3 months. These patients are only eligible in case of measurable disease according to RECIST or cytological/histological proven relapse
* More than two prior lines of chemotherapy.
* Any chemotherapy or other systemic anti-cancer therapy within four weeks prior to randomization.
* Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy

Answer: C