Please select the eligibility criteria that correspond to the clinical trial below.
Title: Two-Arm, Randomized (2:1), Open-Label Phase II/III Study in EpCAM Positive Cancer Patients With Symptomatic Malignant Ascites Using the Trifuncitonal Bispecific Antibody Removab (Anti-EpCAM x Anti-CD3) Versus an Untreated Control Group
Brief Summary: The study will be performed to obtain further efficacy and safety data in order to obtain a marketing authorization (pivotal study). In addition, health economic data are to be collected.


Options:
A: Inclusion Criteria:

1. Written informed consent
2. Female subjects ≥18 years of age
3. Histologically or cytologically confirmed diagnosis of: epithelial ovarian cancer which is platinum resistant or platinum refractory,cancer of the fallopian tube, peritoneal cancer
4. Patients must have failed available standard chemotherapy regimen
5. Prior treatment with at least 2 chemotherapy regimens in advanced tumor setting
6. Performance status ECOG 0 - 2
7. Adequate contraception
8. Adequate organ function
9. Measurable disease according to RECIST criteria.
10. Able to swallow and retain oral medication.
11. Life expectancy of at least 12 weeks.

Exclusion Criteria:

1. Any second malignancy within the last 5 years, with the exception of basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
2. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug.
3. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing
4. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).
5. Prolongation of corrected QT interval (QTc) \>480 msecs.
6. History of any one or more of the following cardiovascular conditions within the past 6 months:

   * Cardiac angioplasty or stenting
   * Myocardial infarction
   * Unstable angina
   * Symptomatic peripheral vascular disease
   * Coronary artery by-pass graft surgery
   * Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
   * History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
7. Macroscopic hematuria
8. Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug
9. Evidence of active bleeding or bleeding diathesis
10. Known endobronchial lesions or involvement of large pulmonary vessels by tumor
11. Prior major surgery or trauma within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
12. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug.
13. Biological therapy, hormonal therapy or treatment with an investigational agent within 28 days or 5 half-lives
14. Prior antiangiogenic therapy.
15. Is unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study
16. Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 and/or that is progressing in severity.
17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
18. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
19. Pregnancy
20. More than 3 different chemotherapy regimens in advanced tumor setting
21. Uncontrolled hypertension
22. History of ischemic event (stroke, myocardial infarction, unstable angina, TIA, symptomatic peripheral vascular disease)
23. History or clinical evidence of thrombo-embolic event
24. History of haemoptysis, cerebral, or clinically significant gastrointestinal haemorrhage in the past 6 months
25. Active bleeding
26. Signs/Suspicion of intestinal obstruction
B: Inclusion Criteria:

* histological confirmed diagnosis cancer
* symptomatic malignant ascites
* EpCAM positive tumor
* EOCG 0-2
* negative pregnancy

Exclusion Criteria:

* acute or chronic infection
* exposure to investigational product, cancer chemo- or radiotherapy within the last 28 days
* previous treatment with mouse monoclonal antibodies
* known or suspected hypersensitivity to Removab or similar antibodies
* inadequate renal function
* inadequate hepatic function (AST, ALt, GTP,\< x ULN; bilirubin \<1.5xULN)
* Platelets \> 80000 cells/mm3; absolute neutrophil count (ANC) \< 1500 cells/mm3
* BMI \< 17
* Patients with reduced nutritional status
* Ileus within the last 30 days
* Brain metastases in cancer history
* Pregnant and nursing women
* history of myocardial infarction, congestive heart failure or relevant cardiac arrhythmia within previous 3 months
* inadequate respiratory function in option of investigator
C: Inclusion Criteria:

* Female aged ≥ 18 years at inclusion
* Histologically confirmed diagnosis of ovarian Sex cord-stromal tumors including the following cell types: granulosa cell tumours (adults and juveniles types), granulosa cell-theca cell tumour, Sertoli-Leydig cell tumours, malignant steroid cell tumours, gynandroblastoma, unclassified SCST and mixed tumours
* Documented relapse of SCST defined by progression of disease (radiologic, clinic or biological progression)
* At least one measurable site of disease as defined by RECIST 1.1

  * Tumours within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence \> 90 days following completion of radiotherapy.
* Patients must have been pre-treated with at least 1 prior line of platinum-based chemotherapy
* Adequate bone marrow, liver and renal functions including the following:

  * Absolute neutrophil count ≥ 1.5 G/L, platelet count ≥ 100 G/L, and hemoglobin ≥ 9 g/dL. Prior transfusion is authorized to keep haemoglobin level to ≥9g/dL
  * AST/ALT ≤ 3 x upper limit of normal (ULN) (or ≤ 5.0 ULN if liver metastasis) and total bilirubin ≤ 1.5 ULN
  * Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance ≥ 50 mL/min according to Cockcroft formula (or to MDRD formula for patients older than 65 years-old).
* Adequate coagulation panel:

  * PT ≤ 1.2 ULN
  * aPTT ≤ 1.5 ULN
  * INR ≤ 1.5 ULN
* Adequate neurologic function: only neuropathy (sensory and motor) grade ≤ 1 (CTCAE v4.3) are allowed
* ECOG Performance status of 0, 1, or 2 (Appendix 5)
* Life expectancy ≥ 4 months
* Satisfactory cardiac function
* Ability to understand and sign informed consent and willingness to comply with the study procedures before study entry
* Women of childbearing potential\* are required to have a negative serum pregnancy test within 7 days prior to study treatment initiation (i.e. Cycle 1 Day 1) and are willing to use adequate contraceptive method during the whole study period and for up to 6 months after the last treatment intake

  \*: Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
  * ≥ 50 years old and naturally amenorrheic for ≥ 1 year
  * Permanent premature ovarian failure confirmed by a specialist gynaecologist

    * Previous bilateral salpingo-oophorectomy or hysterectomy
    * XY genotype, Turner's syndrome, or uterine agenesis
    * Female patient who do not meet at least of the above criteria are defined as women of childbearing potential
* Covered by a medical insurance (in country where applicable)

Exclusion Criteria:

* Prior systemic therapy with bevacizumab
* Active peripheral neuropathy ≥ grade 3 (NCI-CTCAE v4.3)
* Prior history of other malignancies other than ovarian SCST (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the subjects has been free of the disease for at least 3 years or 5 years for breast cancer
* No resolution of specific toxicities related to any prior anti-cancer therapy to grade ≤1, excluding alopecia, according to the NCI-CTCAE v.4.3
* History or evidence of thrombotic or hemorrhagic disorders, including cerebro-vascular accident/stroke or transient ischemic attack or sub-arachnoids' haemorrhage within 6 months prior to first dose of study drugs
* Uncontrolled arterial hypertension (systolic ≥ 150 mmHg or diastolic ≥ 100 mmHg) despite optimal antihypertensive therapy or clinically significant cardiovascular disease including one of the following:

  * Myocardial infarction or instable angina within 6 months prior to first dose of study drugs
  * NYHA grade ≥ II congestive heart failure
  * Serious cardiac arrhythmia requiring medication
  * Peripheral vascular disease ≥ grade 3
* History of bowel obstruction, including sub-occlusive syndrome and history of abdominal fistula, gastro-intestinal perforation or intra-abdominal abscess during the year prior to inclusion
* Prior treatments:

  * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study inclusion or anticipation of need for major surgical procedure during the course of the study
  * Current or recent treatment with another investigational drug within 30 days of first study treatment dosing or within 6 weeks in case of prior nitrozo-urea and or mitomycin C treatment. In case of hormonotherapy , patients will be eligible if hormonotherapy is discontinued within at least 1 week before treatment initiation
  * Current or recent (within 10 days prior to randomization) chronic use of aspirin\> 325 mg/day or use of any other inhibitor of platelet aggregation
  * Chronic treatment (i.e. \> 15 days) with non steroids anti-inflammatory agents unless a washout period of 15 days was observed before the inclusion.
  * Intake of granulocyte growth factor within 3 weeks before study entry
* Presence of hematuria and proteinuria ≥ 2+ (urine dipstick). Patients with ≥ 2+ proteinuria on dipstick at screening should undergo a 24-hour urine collection and will be eligible only if 24-h proteinuria ≤ 1 g
* Untreated evolutive brain metastases
* Active bacteria or fungal infection (grade ≥2, CTC AE V4.3)
* Known HIV1, HIV2 or chronic hepatitis B or C infection
* Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies
* Any contraindications to paclitaxel treatment: for example severe hypersensitivity reactions to paclitaxel, macrogolglycerol ricinoleate (polyoxyl castor oil) or to any of the excipients (Ethanol Citric acid) (refer to Taxol® SPC for further details)
D: Inclusion Criteria:

* Patients with epithelial Ovarian cancer in late relapse

Answer: B