FOCUS: PCC + Bevacizumab + CA4P Versus PCC + Bevacizumab + Placebo for Subjects With Platinum Resistant Ovarian Cancer

Inclusion:

1. Signed informed consent form (ICF)
2. Age ≥ 18 years (Age ≥ 19 years if required by local regulatory authorities)
3. ECOG PS of 0-1
4. Histologically or cytologically-confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer in recurrent stage
5. prOC (platinum-resistant ovarian cancers) defined as progression within \> 1 to \< 6 months (+ 2 weeks) of completing previous cycle of primary platinum-based therapy, or during or within \< 6 months (+ 2 weeks) of starting additional platinum based therapies
6. Received ≥ 1 but ≤ 3 prior platinum-based regimens
7. Measurable disease according to RECIST 1.1
8. Left ventricular ejection fraction (LVEF) greater than or equal to at least 45% at baseline assessment if subject is receiving PLD, and/or anthracycline is a concomitant medication
9. No evidence of active (progressing) brain metastasis. (Treated brain metastasis allowed with a posttreatment magnetic resonance imaging (MRI) or Computed Tomography (CT) of brain showing no active (progressing) brain metastasis). Treatment of brain metastasis may include surgery, radiosurgery (linear accelerator (LINAC), gamma knife), or whole brain irradiation. Surgery for brain metastasis must be \> 8 weeks from study entry
10. Hemoglobin \> 9 g/dl. Erythroid growth factors should not have been used in the 2 weeks prior to study entry. Red blood cell transfusions are permitted to maintain the hemoglobin level \> 9 g/dl
11. Adequate bone marrow function in the investigator's opinion
12. Adequate hepatic function defined by the following:

    * Total bilirubin \< 2 x Upper Limit of Normal (ULN)
    * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 X ULN for the referenced lab (\< 5 X ULN for subjects with liver metastases)
13. Adequate renal function defined by the following:

    \- Serum creatinine \< 2 X ULN for the referenced lab
14. Subjects of childbearing potential must have a negative serum pregnancy test prior to study entry and must be practicing a highly effective form of contraception
15. At least 2 weeks since prior radiotherapy and has recovered from any Grade 3 toxicities
16. Life expectancy ≥ 12 weeks

Exclusion:

1. Subjects who have received prior CA4P therapy
2. Previously having failed treatment with bevacizumab combined with the intended PCC.

   \- For clarity: Investigators should not select a bevacizumab + PCC combination for the FOCUS trial if the patient has previously failed that same regimen, however they may select a new PCC regimen to combine with bevacizumab. For example, a patient who failed bevacizumab + weekly paclitaxel would be allowed to enroll in FOCUS only if they are assigned to bevacizumab + PLD for the study.
3. Previous treatment with greater than three traditional chemotherapy treatment regimens
4. Untreated brain metastasis or leptomeningeal brain metastasis
5. Solid organ or bone marrow transplant
6. Primary platinum-refractory disease (defined as progression during dosing or within one (1) month of completing the last cycle of patients first platinum-containing regimen)
7. \> Grade 2 peripheral neuropathy
8. Current thrombotic or hemorrhagic disorder/event or history of prior event within 6 months of start of Screening
9. History of prior cerebrovascular event, (including transient ischemic attack) within 6 months of start of Screening
10. Recent history (within 6 months of start of Screening) of angina pectoris, myocardial infarction (including non-Q wave MI), or NYHA Class III and IV congestive heart failure
11. History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\<60 bpm), heart block (excluding 1st degree block, benign PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG
12. Known uncontrolled HIV infection
13. Uncontrolled, clinically significant active infection
14. Serious non-healing wound, ulcer or bone fracture
15. Subjects with known hypersensitivity to any of the components of CA4P, paclitaxel, PLD, or bevacizumab (paclitaxel and PLD dependent on whether PI plans they will be dosed with that PCC)
16. Subjects who are currently or planning on receiving concurrent investigational therapy or who have received investigational therapy for any indication within 30 days of the first scheduled day of dosing
17. Subjects with any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to provide informed consent, cooperate and participate in the study, or to interfere with the interpretation of the study results
18. Subjects with other invasive malignancies, with the exception of non-melanoma skin cancer, or with previous cancer treatment that contraindicates this protocol therapy within last 3 years
19. Prior radiation therapy to the pelvis or abdomen within 4 weeks of entry into the study
20. History of fistula, gastrointestinal (GI) perforation or intra-abdominal abscess, or invasive disease/metastases of the bowel which in the investigators opinion may increase the risk of GI perforation with bevacizumab treatment.
21. Uncontrolled hypertension (HTN)

    \- Sustained BP greater than 150 mmHG SBP / 100 mmHG DBP
22. Uncontrolled elevated proteinuria levels in the investigator's opinion
23. Corrected QT interval (\[QTc\] Fridericia) \> 480 ms
24. Significant vascular disease or recent peripheral arterial thrombosis
25. Subjects with active bleeding or pathologic conditions that carry high risk of bleeding
26. Subjects who are pregnant or lactating