Paclitaxel and Bevacizumab With or Without Emactuzumab in Treating Patients With Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Condition: Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fallopian Tube Undifferentiated Carcinoma; Malignant Ovarian Brenner Tumor; Ovarian Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Ovarian Undifferentiated Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Brenner Tumor; Recurrence
Intervention: Bevacizumab; Emactuzumab; Laboratory Biomarker Analysis; Paclitaxel; Pharmacological Study
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Correlative studies
Intervention MeSH terms: Paclitaxel; Bevacizumab; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies the side effects of paclitaxel and bevacizumab with or
      without emactuzumab and how well they work in treating patients with ovarian, fallopian tube,
      or primary peritoneal cancer that has come back after treatment with platinum chemotherapy.
      Monoclonal antibodies, such as emactuzumab, block tumor growth in different ways by targeting
      certain cells. Drugs used in chemotherapy, 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. Bevacizumab may prevent the growth of new blood vessels that
      tumors need to grow. Giving emactuzumab with paclitaxel and bevacizumab may work better in
      treating ovarian, fallopian tube, or primary peritoneal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent obtained prior to initiation of any study-specific procedures
             and treatment as confirmation of the patient's awareness and willingness to comply
             with the study requirements (inclusive of 2 biopsies, one at baseline and if they
             qualify, one pre-randomization for part 2B)

          -  Women 18 years of age or older

          -  Histologically confirmed and documented disease to include: adenocarcinoma NOS (not
             otherwise specified), clear cell adenocarcinoma, endometrioid adenocarcinoma,
             malignant Brenner's tumor, mixed epithelial carcinoma, mucinous adenocarcinoma, serous
             adenocarcinoma, transitional cell carcinoma, and undifferentiated carcinoma

          -  Patients must have platinum-resistant disease, (defined as progression within < 6
             months from completion of a minimum of 4 platinum therapy cycles (+ 7 days); the date
             should be calculated from the last administered dose of platinum therapy)

          -  Patients must have disease that is measurable according to RECIST 1.1 or assessable
             according to the GCIG CA-125 criteria and require chemotherapy treatment; part 1:
             patients must have one or more measurable target lesion; part 2: patients must have
             two or more measurable target lesions; measurable disease is defined at least one
             lesion that can be accurately measured in at least one dimension (longest dimension to
             be recorded); each 'target' lesion must be >= 20 mm when measured by conventional
             techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic
             resonance imaging (MRI), or >= 10 mm when measured by spiral CT

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Newly obtained core or excisional biopsy of a tumor lesion for part 2A and if they
             qualify, one pre-randomization biopsy for part 2B

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >=9 g/dL or >= 5.6 mmol/L

          -  Creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 X
             institutional upper limit of normal (ULN)

          -  Total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGOT]) =< 2.5 X
             ULN OR =< 5 X ULN for subjects with liver metastases

          -  International normalized ratio (INR)/prothrombin time (PT) =< 1.5 X ULN (unless
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time [PTT] is within therapeutic range of intended use of anticoagulants)

          -  PTT =< 1.5 X ULN (unless subject is receiving anticoagulant therapy as long as PT or
             PTT is within therapeutic range of intended use of anticoagulants)

          -  Life expectancy of >= 12 weeks

        Exclusion Criteria:

          -  Patients who have disease progression prior to completion of intended frontline
             therapy, including patients demonstrating disease progression after interval
             cytoreduction

          -  Non-epithelial, including malignant mixed Mullerian tumors

          -  Ovarian tumors with low malignant potential (i.e. borderline tumors)

          -  For part 2 patients only: 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, or early stage endometrial cancer (stage
             IA/B, grade 1 or 2, endometrioid histology)

          -  Previous treatment with > 2 anticancer regimens for ovarian cancer

          -  Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3
             weeks prior to initiation of study treatment, with the following exceptions:
             hormone-replacement therapy or oral contraceptives; tyrosine kinase inhibitors (TKIs)
             that have been discontinued > 7 days prior to cycle 1, day 1; screening scans must be
             obtained after discontinuation of prior TKIs

          -  Any prior radiotherapy to the pelvis or abdomen

          -  Surgical procedure (including open biopsy, surgical resection, wound revision, or any
             other major surgery involving entry into a body cavity) 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; minor surgical procedures including
             placement of a vascular access device, within 2 days of the first study treatment

          -  Previous exposure to murine CA-125 antibody (only applicable to those patients with
             non-measurable disease by RECIST)

          -  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

          -  Treatment with systemic immunosuppressive medications (including, but not limited to,
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF
             agents within 2 weeks prior to cycle 1, day 1; patients who have received acute and/or
             lowrolment, or anticipation of need for major surgical, a one-time dose of
             dexamethasone for nausea or chronic use of =< 10 mg/day of prednisone or
             dose-equivalent corticosteroid) may be enrolled in the study after discussion with and
             approval by the medical monitor; the use of inhaled corticosteroids and
             mineralocorticoids (e.g., fludrocortisone) is allowed; prior corticosteroids as
             anti-cancer therapy within a minimum of 14 days of first receipt of study drug

          -  Received therapeutic oral or IV antibiotics within 2 weeks prior to cycle 1, day 1;
             patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
             infection or chronic obstructive pulmonary disease) are eligible

          -  Patients with 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

          -  Patients with known auto-immune disease

          -  Patients with known history of human immunodeficiency virus (HIV), hepatitis B virus
             (HBV) and hepatitis C virus (HCV) infection

          -  Patient has received an organ transplant

          -  Patient has a history of hematological malignancy within the last 5 years prior to
             study entry; prior allogeneic bone marrow transplantation or prior solid organ
             transplantation

          -  Patient has a history of hematological malignancy within the last 5 years prior to
             study entry

          -  History of or active autoimmune disease including, but not limited to, systemic lupus
             erythematous, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, and vasculitis or
             glomerulonephritis; patients with autoimmune thyroid disease on a stable thyroid
             replacement regimen; controlled vitiligo, eczema, psoriasis, or seborrheic dermatitis
             with only dermatologic manifestations; or controlled type I diabetes on a stable
             insulin regimen may be eligible for the study with approval by the medical monitor

          -  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

          -  Pre-existing peripheral neuropathy >= Common Terminology Criteria (CTC) grade 2 for
             those patients who received prior paclitaxel

          -  Spinal cord compression not definitively treated with surgery and/or radiation or
             previously diagnosed and treated spinal cord compression without evidence that disease
             has been clinically stable for >= 2 weeks prior to screening

          -  Increased corrected QT (QTc) interval (QTc > 470 ms), patients with baseline resting
             bradycardia < 45 beats per minute (bpm), or baseline resting tachycardia > 100 bpm

          -  Family history of long QT syndrome or other risk factors for torsades de pointes,
             and/or the use of concomitant medications that prolong the QT/QTc interval

          -  Signs or symptoms of serious active infection requiring oral or i.v. antibiotics
             within 2 weeks prior to cycle 1 day 1 and/or hospitalization at study entry including,
             but not limited to, hospitalization for complications of infection, bacteremia, active
             tuberculosis or severe pneumonia

          -  Pregnant or lactating females; serum pregnancy test to be assessed within 7 days prior
             to study treatment start, or within 14 days (with a confirmatory urine pregnancy test
             within 7 days prior to study treatment start)

          -  For women who are not postmenopausal (< 12 months of non therapy-induced amenorrhea,
             with no identified cause other than menopause) and have not undergone surgical
             sterilization (removal of ovaries and/or uterus): agreement to remain abstinent
             (refrain from heterosexual intercourse) or use two adequate non hormonal methods of
             contraception, including at least one method with a failure rate of < 1% per year,
             during the treatment period and for at least 4 months after the last dose of study
             drug

          -  Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year
             include bilateral tubal ligation, male sterilization, established, proper use of
             hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine
             devices, and copper intrauterine devices; the reliability of sexual abstinence needs
             to be evaluated in relation to the duration of the clinical trial and the preferred
             and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation,
             symptothermal, or postovulation methods) and withdrawal are not acceptable methods of
             contraception

          -  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

          -  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); significant vascular disease (e.g., aortic aneurysm, requiring surgical
             repair or recent peripheral arterial thrombosis) within 6 months prior of study
             enrollment; prior history of hypertensive crisis or hypertensive encephalopathy

          -  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

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month
             of study enrollment for any tumor type

          -  Non-healing wound, ulcer or bone fracture

          -  Known hypersensitivity to any of the study drugs or excipients

          -  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