PRIMARY OBJECTIVES:~I. To assess the safety and tolerability of the combination of weekly anetumab ravtansine (anetumab) and bi-weekly bevacizumab.~II. To determine whether the progression free survival (PFS) of the combination weekly anetumab and bi-weekly bevacizumab is superior to weekly paclitaxel and bi-weekly bevacizumab.~SECONDARY OBJECTIVES:~I. To determine the overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.~II. To evaluate the pharmacokinetic (PK) profiles of weekly anetumab in serum and in peripheral blood mononuclear cells (PBMCs).~III. To evaluate anti-drug antibody (ADA) titers (only for patients receiving anetumab).~IV. To evaluate mononuclear phagocyte system (MPS) function, Fc-gamma receptors (FcgammaRs), hormone and chemokine mediators.~V. To correlate the expression of CA125 (immunohistochemistry [IHC] & serum) with mesothelin expression in archival tissue and circulating megakaryocyte potentiating factor (MPF).~VI. To investigate blood-based angiome profiling as a potential biomarker. VII. To characterize the molecular profile of archival tumor tissue using the Oncomine panel, and explore whether genomic mutations such as BRCA1/2 and homologous repair deficiency status are associated with clinical outcome.~EXPLORATORY OBJECTIVE:~I. To assess tumor tissue-based VEGF-dependent gene expression signature as a biomarker of response.~OUTLINE:~PHASE I: Patients receive anetumab ravtansine intravenously (IV) over 1 hour on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~PHASE II: Patients are randomized to 1 of 2 groups.~GROUP I: Patients receive anetumab ravtansine and bevacizumab as in Phase I.~GROUP II: Patients receive paclitaxel on days 1, 8, 15, and 22 and bevacizumab over 30-90 minutes IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30-37 days and then every 8 weeks thereafter.
This phase II trial studies the side effects of bevacizumab and anetumab ravtansine or paclitaxel in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that does not respond to treatment (refractory). Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Anetumab ravtansine is a drug that targets a protein in the body called mesothelin, which can be found in some ovarian, pancreatic and other tumors. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving bevacizumab and anetumab ravtansine or paclitaxel may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.