Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase II Randomized Trial of the Polo-like Kinase 1 Inhibitor BI 6727 Monotherapy Versus Investigator´s Choice Chemotherapy in Ovarian Cancer Patients Resistant or Refractory to Platinum-based Cytotoxic Therapy
Brief Summary: This is an international, randomized phase II trial. The aim is to assess the efficacy and the safety of BI 6727 Versus investigator's best choice single agent cytotoxic in recurrent third and fourth lines platinum resistant/refractory ovarian cancer.

100 patients will be randomised at the study entry to receive either BI 6727 (Arm A: 50 patients) or non-platinum single agent cytotoxic (Arm B: 50 patients) Treatment will be continued until disease progression or unacceptable toxicity. Primary endpoint: disease control rate at week 24 according to Response Evaluation Criteria In Solid Tumours version 1.1.

Secondary endpoints: efficacy (progression free survival, overall survival, biological tumour response, biological progression free survival assessed by serum CA 125 according to Gynecologic Cancer Intergroup criteria, safety according to the NCI CTCAE v.3, disease symptoms control assessed by the EORTC QLQ-C30, QLQ-OV28 and individual symptoms questionnaires, pharmacokinetics of BI 6727.

Others endpoints: biomarkers and pharmacogenetics analysis (optional)


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:

* Measurable disease by CT or MRI.
* At least 1 "target lesion" to be used to assess response as defined by GOG RECIST criteria.
* ECOG performance status of 0 or 1.
* Patient provides voluntary written informed consent.
* At least 18 years of age.
* Negative serum pregnancy test.
* Recovered from any recent surgery for at least 30 days and is free of active infection.
* Received the following prior therapy at time of enrollment:
* Must have had 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin or organoplatinum. Initial therapy may have included high-dose therapy, consolidation, or extended therapy. Patient should be defined as recurrent or progression of disease within 6 months of last platinum chemotherapy.
* May have had 1 additional cytotoxic or non-cytotoxic chemotherapy regimen.
* Must have adequate hematologic and hepatic function.

Exclusion Criteria:

* Previously received bevacizumab.
* History of other invasive malignancy with the exception of nonmelanoma skin cancer.
* ECOG performance status of 2, 3, or 4.
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study. Patient must be bevacizumab naïve.
* Blood pressure of \>150/100 mm Hg on antihypertensive medications.
* Prior history of hypertensive crisis or hypertensive encephalopathy.
* Diagnosed with unstable angina per NYHA or Grade 2 or greater congestive heart failure.
* History of myocardial infarction within 6 months of enrollment.
* History of stroke or transient ischemic attack within 6 months prior to study enrollment.
* Clinically significant vascular disease (e.g., aortic aneurysm, aortic dissection)or symptomatic peripheral vascular disease.
* Bleeding diathesis or coagulopathy.
* Presence of CNS or brain metastases.
* Pre-existing peripheral neuropathy of Grade ≥ 2.
* A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.
* A partial or complete small or large bowel obstruction demonstrated radiologically within 3 months prior to study enrollment.
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
* Positive pregnancy test or is lactating.
* History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
* Serious, non-healing wound, ulcer, or bone fracture.
* Serious intercurrent medical or psychiatric illness, including serious active infection.
* Inability to comply with study and/or follow-up procedures.
* Life expectancy of less than 12 weeks.
* Proteinuria at screening as demonstrated by either:
* Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR
* Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
* Known hypersensitivity to any component of bevacizumab.
C: Inclusion criteria:

1. Confirmed recurrent epithelial ovarian carcinoma, peritoneal carcinoma or fallopian tube carcinoma.
2. Platinum resistant or platinum refractory disease.
3. Eastern Collaborative Oncology Group performance status \< = 2.
4. Life expectancy \> = 3 months.
5. At least one measurable lesion (Response Evaluation Criteria In Solid Tumours version 1.1).
6. Adequate hepatic, renal and bone marrow functions.
7. signed written informed consent prior to admission to the study.

Exclusion criteria:

1. Contre-indications for cytotoxic treatment according to the Summary of Product Characteristics (Arm B).
2. Clinical evidence of active brain metastasis or leptomeningeal involvement.
3. Other malignancy currently requiring active therapy.
4. QTc prolongation according to Fridericia formula deemed clinically relevant by the investigator (e.g., congenital long QT syndrome, QTc according to Fridericia formula \> 470 ms).
5. Hypersensitivity to one of the trial drugs or the excipients.
6. Serious illness or concomitant non- oncological disease.
7. Systemic anticancer therapy within 4 weeks before the start of the study.
8. Evidence of ileus sor sub ileus.
D: Inclusion Criteria:

* Histologically proven epithelial ovarian cancer, epithelial fallopian tube cancer, or primary peritoneal cancer
* Prior treatment with only 1 platinum based chemotherapy regimen
* Eastern Cooperative Oncology Group status of not more than 2
* Progression more than 6 months after the start of initial chemotherapy treatment

Exclusion Criteria:

* Treatment with more than 1 prior chemotherapy regimen
* Progression within 6 months after starting initial chemotherapy
* Prior exposure to anthracyclines
* Unwilling or unable to have central venous catheter
* Known clinically relevant central nervous system metastasis

Answer: C