Cyclodextrin-Based Polymer-Camptothecin CRLX101 with or without Bevacizumab in Treating Patients with Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

Inclusion Criteria

• GROUP A MONOTHERAPY
• Participants must have histologically or cytologically confirmed invasive epithelial ovarian, tubal or primary peritoneal cancer; all histologies (including serous, mucinous, endometrioid, clear cell, malignant mixed mesodermal tumors [MMMTs] and mixed histologies) are eligible
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
• Patients may be platinum-sensitive or resistant; group A (monotherapy cohort); participants may have received up to 3 prior cytotoxic chemotherapies, i.e., second or third line; there is no limit to the number of lines of prior biologic or hormonal therapies they may have had; patients may be platinum-sensitive or resistant or refractory
• Participants may not have received any prior camptothecin, including but not limited to: topotecan, irinotecan
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
• Participants with gross hematuria are not eligible; patients with microscopic hematuria are eligible
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• ONLY APPLIES TO PATIENTS IN GROUP B (COMBINATION THERAPY)
• Participants may not have received any prior anti-vascular endothelial growth factor (VEGF) antibody or inhibitor including but not limited to bevacizumab
• Participants must have platinum-resistant disease, (defined as progression within < 6 months from completion of a minimum of 4 platinum therapy cycles; the date should be calculated from the last administered dose of platinum therapy)
• Participants may have received up to 2 prior cytotoxic chemotherapies; there is no limit to the number of lines of prior biologic or hormonal therapies they may have had; patients must be platinum resistant
• Hemoglobin < 9 g/dl; patients may be transfused to maintain hemoglobin values > 9 g/dl
• Activated partial thromboplastin time (aPTT) > 1.5 x ULN (patients on heparin treatment must have an aPTT between 1.5 - 2.5 x ULN), or
• International normalized ratio (INR) > 1.5; (in patients receiving anticoagulants [such as warfarin] INR must be between 2.0 and 3.0 in two consecutive measurements 1-4 days apart)
• Urine dipstick for proteinuria < 2+; patients with < 2+ proteinuria on baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in the 24-hour urine; alternatively, proteinuria testing can be performed according to local standards
• ONLY APPLIES TO PATIENTS IN GROUP C (CORRELATIVE COHORT)
• Participants are not required to have measurable disease but must have an accessible tumor to biopsy
• Participants may have received any number of prior cytotoxic chemotherapies; there is no limit to the number of lines of prior biologic or hormonal therapies they may have had; patients may be platinum-sensitive or resistant or refractory
• Life expectancy of greater than 1 month
• Participants may have brain metastasis
• Participants must consent to collection of blood, ascites fluid and tumor tissue samples prior to first dose of CRLX101 and at least one additional sample collection after the second dose (archived material is acceptable for collection prior to first dose of CRLX101)

Exclusion Criteria

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Participants may not be receiving any other study agents
• Participants with known brain metastases should be excluded from this clinical trial; does not apply to group C
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan or irinotecan
• Participants with gross hematuria are ineligible
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with CRLX101
• Individuals with a history of a different malignancy are ineligible except for the patients with concurrent non-invasive endometrial cancer; individuals with a history of other malignancies are eligible if they have been disease-free for at least 2 years, were treated with curative intent, and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 2 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
• Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible
• ONLY APPLIES TO PATIENTS IN GROUP B
• Patients whose disease was refractory to their previous platinum treatment; refractory disease is defined as those patients who progressed during the preceding platinum treatment
• History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast
• Patients must not have prior, current or planned treatment as defined below: * Previous treatment with > 2 anticancer regimens * Any prior radiotherapy to the pelvis or abdomen * Surgery (including open biopsy) within 4 weeks prior to the start of study, or anticipation of the need for major surgery during study treatment * Minor surgery procedures, within 24 hours prior to the first study treatment * Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (> 325 mg/day) * Current or recent treatment with another investigational drug within 30 days of first study treatment dosing or earlier participation in this study * Chronic daily treatment with corticosteroids (dose > 10 mg/day methylprednisolone equivalent), excluding inhaled steroids
• History or evidence upon physical/neurological examination of central nervous system (CNS) disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures); symptomatic CNS metastasis
• History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident (CVA)/stroke or transient ischemic attack (TIA) or sub-arachnoid hemorrhage within =< 6 months prior to the first study treatment
• History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess; evidence of recto sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
• Non-healing wound, ulcer or bone fracture
• Serious active infection requiring i.v. antibiotics and/or hospitalization at study entry
• Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer, etc.), physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications
• Uncontrolled hypertension (sustained systolic > 150 mmHg and/or diastolic > 100 mmHg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including: * Myocardial infarction or unstable angina within =< 6 months prior to the first study treatment * New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF) * Serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia) * Peripheral vascular disease > grade 3 (i.e. symptomatic and interfering with activities of daily living requiring repair or revision)