Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicenter, Randomised, Double-blind Phase III Trial to Investigate the Efficacy and Safety of BIBF 1120 in Combination With Carboplatin and Paclitaxel Compared to Placebo Plus Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer
Brief Summary: The trial will be performed to evaluate if BIBF 1120 in combination with paclitaxel and carboplatin is more effective than placebo in combination with paclitaxel and carboplatin in first-line treatment of patients with advanced ovarian cancer. Safety information about BIBF1120/paclitaxel/carboplatin will be obtained.


Options:
A: Inclusion Criteria:

* Advanced ovarian cancer with positive BRCA1 or BRCA2 status
* Progressive or recurrent disease after platinum-based chemotherapy
* Measurable disease by RECIST

Exclusion Criteria:

* Previous anthracycline treatment
* Brain metastases
* Less than 28 days since last treatment used to treat the disease
* Considered a poor medical risk due to a serious uncontrolled disorder
B: Inclusion Criteria:

* Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
* Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial.
* Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen.
* Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response.
* For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response.
* Have sufficient archival tumor tissue for analysis.

Exclusion Criteria:

* History of prior cancer except for non-melanoma skin cancer, breast cancer curatively \> 3 years ago, curatively treated solid tumor (\>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer.
* Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.
* Untreated or symptomatic central nervous system metastases.
* Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug.
* Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.
C: Inclusion criteria:

* first diagnosis of histologically confirmed epithelial ovarian cancer, fallopian tube or primary peritoneal cancer
* International Federation of Gynecology and Obstetrics (FIGO) Stages IIB - IV
* females, age 18 years or older
* life expectancy of at least 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* prior surgery, defined as either (a) debulking surgery with maximum surgical effort at cytoreduction with the goal of no residual disease or (b) biopsy or limited surgery in patients with stage IV disease for whom surgical debulking was not considered appropriate, if diagnosis is confirmed by histology and no surgery is planned prior to disease progression (including interval debulking surgery)
* patient has given written informed consent which must be consistent with the International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local legislation
* planned application of first dose of chemotherapy after wound healing, but no later than 10 weeks after surgery

Exclusion criteria:

* histologic diagnosis of a benign or borderline tumour or of a malignant tumour of non-epithelial origin of the ovary, the fallopian tube or the peritoneum
* planned surgery within 124 weeks after randomisation in this trial, including interval debulking surgery
* clinically relevant non-healing wound, ulcer or bone fracture
* clinical symptoms or signs of gastrointestinal obstruction that require parenteral nutrition or hydration
* brain metastases
* pre-existing sensory or motor neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher, except due to trauma
* history of major thromboembolic event
* known inherited or acquired bleeding disorder
* significant cardiovascular diseases
* clinically relevant pericardial effusion
* history of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months
* inadequate safety laboratory values
* serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy, including Hepatitis B, Hepatitis C, Human Immunodeficiency Virus (HIV)
* poorly controlled diabetes mellitus or other contraindication to high dose corticosteroid therapy
* gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
* other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included if adequately treated: non-melanomatous skin cancer, cervical carcinoma in situ, carcinoma in situ of the breast, low risk endometrial cancer
* prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy)
* prior systemic cytotoxic chemotherapy
* prior treatment with BIBF 1120 or any other angiogenesis inhibitor
* prior radiotherapy
* serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease or a laboratory abnormality that may increase the risk associated with study participation or study drug administration
* Women of childbearing potential who are sexually active and not using a highly effective method of birth control during the trial and for at least twelve months after the end of active therapy.
* pregnancy or breast feeding
* psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
* active alcohol or drug abuse
* patients unable to comply with the protocol
* any contraindications for therapy with paclitaxel or carboplatin
* treatment with other investigational drugs or participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial
D: Inclusion Criteria:

* Advanced, progressive, recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, which has recurred following at least one platinum-containing regimen.
* Progressive disease according to RECIST 1.1 or GCIG criteria within 3-12 months of completing platinum containing therapy, although this need not be the immediately preceding regimen.
* World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1).
* Measurable disease (RECIST 1.1 (Appendix 2) or Progressive Disease (PD) according to CA125 GCIG criteria with non-measurable disease on CT scan.
* Life expectancy of at least 12 weeks.
* Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient receives the first dose of Investigational Medicinal Product (IMP):

  * Haemoglobin (Hb) ≥ 90 g/L
  * Absolute neutrophil count ≥ 1.5 x 109/L
  * Platelet count ≥ 100 x 109/L
  * Serum potassium within normal range
  * Bilirubin ≤ 1.5 x upper limit of normal (ULN)
  * Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 2.5 x ULN unless raised due to hepatic metastatic disease in which case up to 5 x ULN is permissible
  * Either: Calculated creatinine clearance ≥ 40 mL/min (uncorrected value) Or: Isotope clearance measurement ≥ 40 mL/min (corrected)
  * Activated partial thromboplastin time (aPTT) ≤ 1.2 x ULN
  * Prothrombin Time (PT) or International normalised ratio (INR) ≤ 1.3 x ULN
  * Urine protein dipstick of less than or equal to 2+, or if 2+ or greater the patient must have a 24 hour urinary protein value of less than 2 g.
  * Clinically euthyroid.
  * Aged 18 years or over at the time of consent.
  * Written (signed and dated) informed consent and capable of co-operating with treatment and follow-up.
  * Patients can have received bevacizumab prior to trial entry providing that the last dose was administered at least 6 months before the first dose of IMP.

Exclusion Criteria:

* Radiotherapy, surgery or tumour embolisation within 28 days before the first dose of IMP
* Endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C and six weeks for investigational medicinal products) before the first dose of IMP.
* Ongoing grade ≥ 2 toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Chief and Principal Investigators should not exclude the patient; and grade 1 or 2 neurotoxicity considered to be due to paclitaxel.
* Female patients who are able to become pregnant (or are already pregnant or lactating). Those who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.
* Major thoracic or abdominal surgery from which the patient has not yet recovered.
* At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
* Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
* History of any of the following cardiovascular conditions within the last six months:

  * Coronary revascularisation (percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG))
  * Acute coronary syndrome (myocardial infarction (MI), unstable angina)
  * Symptomatic peripheral vascular disease
  * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (Appendix 4)
* Patients who have sustained hypertension, defined as a systolic blood pressure (SBP) of \> 140 mm Hg or diastolic blood pressure (DBP) of \> 90 mm Hg, on three occasions.
* ECG with evidence of clinically significant abnormalities.
* Patients with a QTc\> 480ms or taking any drug known to prolong the QTc interval that cannot be stopped for the duration of the trial (Appendix 4).
* Patients with pathologic bradycardia (\<60 b/m in non-athletes), heart block (excluding first-degree block, being PR interval prolongation only).
* History of cerebrovascular accident (including transient ischaemic attack (TIA)), pulmonary embolism or untreated deep vein thrombosis (DVT) within the past six months. Patients with recent DVT or pulmonary embolism who have been treated with therapeutic anti-coagulant agents for at least six weeks will be eligible, provided their INR (if taking oral anti-coagulants) has been stable for this period of time.
* 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-convulsant medication for six months prior to the first dose of IMP.
* Clinically significant abnormalities that may increase the risk of gastrointestinal bleeding or perforation, including but not limited to:

  * Bleeding: Active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, Inflammatory bowel disease (Crohn's disease, ulcerative colitis);
  * Perforation: History of abdominal fistula or large pelvic mass; gastrointestinal perforation or intra-abdominal abscess within four weeks prior to first dose of IMP; previous bowel surgery which is judged by the investigator to increase significantly the risk of gastrointestinal complications from trial treatment
* Evidence of active bleeding or bleeding diathesis.
* Transfusion within one week prior to first dose of IMP.
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
* Clinically significant haemoptysis, within eight weeks before the first dose of IMP.
* Previous treatment with pazopanib.
* Any participant that is participating in (or plans to participate in) another interventional clinical trial, whilst taking part in this Phase Ib/II study of fosbretabulin and pazopanib. Participation in an observational trial would be acceptable.
* Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
* Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and no evidence of recurrence of other malignancy for at least 2 years.
* Hypersensitivity to Pazopanib or any of it's excipients

Answer: C