A Randomized Phase II Evaluation of Single-Agent Bevacizumab (IND #7921) (NSC #704865) and Combination Bevacizumab With Fosbretabulin Tromethamine (CA4P) (NSC #752293) in the Treatment of Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Inclusion Criteria:

- Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma

- Histologic documentation of the original primary tumor is required via the
pathology report

- Patients must have measurable disease or detectable (non-measurable) disease:

- Measurable disease defined as at least one lesion that can be accurately
measured in at least one dimension (longest dimension to be recorded)

- Each lesion must be ≥ 10 mm when measured by CT scan, MRI or caliper
measurement by clinical exam, OR ≥ 20 mm when measured by chest x-ray

- Lymph nodes must be ≥ 15 mm in short axis when measured by CT scan or MRI

- Detectable disease defined as no measurable disease but has at least one of the
following conditions:

- Baseline values of CA-125 at least 2 times upper limit of normal

- Ascites and/or pleural effusion attributed to tumor

- Solid and/or cystic abnormalities on radiographic imaging that do not meet
RECIST 1.1 definition for target lesions

- Patients in the measurable disease cohort must have at least one "target lesion" to
be used to assess response on this protocol as defined by RECIST 1.1

- Tumors within a previously irradiated field will be designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence at least 90 days following completion of radiation therapy

- Prior therapy:

- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound; this initial treatment may have included
intraperitoneal therapy, consolidation, non-cytotoxic (biologic/targeted agents,
such as bevacizumab) or extended therapy administered after surgical or
non-surgical assessment

- Patients are allowed to receive, but are not required to receive, two additional
cytotoxic regimens for management of recurrent or persistent disease, with no
more than 1 non-platinum, non-taxane regimen

- Patients are allowed to receive, but are not required to receive, non-cytotoxic
(biologic/targeted agents, such as bevacizumab) therapy as part of their primary
treatment regimen; patients must have NOT received any non-cytotoxic therapy
(biologic/targeted agents) for management of recurrent or persistent disease
(e.g., GOG protocol 170 series drugs or bevacizumab)

- For the purposes of this study, Poly (ADP-ribose) polymerase (PARP) inhibitors
will be considered "cytotoxic", and prior treatment with PARP inhibitors for
primary or recurrent disease WILL be allowed (either alone or in combination
with chemotherapy) (12/19/2011)

- Patients with both platinum-sensitive and platinum-resistant disease are
eligible; patients with platinum-refractory disease are NOT eligible;
platinum-refractory disease is defined as patients who have progression of
disease during the preceding platinum treatment

- PFI for the most recent platinum therapy will need to be calculated before
enrollment onto this study for stratification purposes (i.e. balanced
randomization)

- Patients who have a PFI =< 182 days (26 weeks) are defined as "platinum
resistant"; patients who have 182 < PFI =< 365 days are defined as "GOG platinum
sensitive"; finally, patients with PFI > 365 days are defined as "platinum
sensitive"

- Not eligible for a higher-priority GOG protocol, if one exists

- Any active GOG Phase III protocol or Rare Tumor protocol for the same patient
population

- No history or evidence upon physical examination of CNS disease, including primary
brain tumor or any brain metastases

- Performance status (PS) 0-2 (for patients who had 1 prior treatment) OR PS 0-1 (for
patients who had 2-3 prior treatments)

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Creatinine ≤ 1.5 times upper limit of normal (ULN)

- Potassium ≥ 4.0 mmol/L*

- Magnesium ≥ 1.8 mmol/L*

- Calcium ≥ 8.4 mg/dL*

- NOTE: *Correction with supplements allowed.

- Bilirubin ≤ 1.5 times ULN

- AST ≤ 3 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- INR ≤ 1.5 times ULN (or an in-range INR, usually between 2 and 3, if a patient is on
a stable dose of therapeutic warfarin)

- PTT ≤ 1.5 times ULN

- Urine protein: if protein is 2+ or higher, a 24-hour urine protein should be obtained
and the level must be < 1,000 mg (< 1.0 g/24 hrs)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Free of acute hepatitis and active infection requiring parenteral antibiotics (with
the exception of uncomplicated urinary tract infection [UTI])

- No other invasive malignancy except non-melanoma skin cancer, localized cancer of the
breast, head and neck, or skin provided disease was curatively treated and patient
remains free of recurrent or metastatic disease for more than 3 years

- No serious non-healing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within the past 90 days

- No active bleeding or pathologic conditions that carry high-risk of bleeding, such as
known bleeding disorder, coagulopathy, or tumor involving major vessels

- No seizures that are not controlled with standard medical therapy, history of
cerebrovascular accident (CVA, stroke), TIA, or subarachnoid hemorrhage within 6
months prior to the first date of treatment on this study

- No clinically significant cardiovascular disease, including any of the following:

- Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg
or diastolic BP > 90 mm Hg, despite antihypertensive medications

- History of Torsade de Pointes, ventricular tachycardia or fibrillation,
pathologic sinus bradycardia (< 60 bpm), heart block (excluding 1st degree block
PR interval prolongation only), congenital long QT syndrome, new ST segment
elevation or depression, or new Q waves on ECG

- Patients with QTc >= 470 msec

- Stable regimen of antidepressants of the selective serotonin reuptake
inhibitor (SSRI) class is allowed

- Myocardial infarction or unstable angina within 6 months prior to registration

- NYHA Class II or greater congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Asymptomatic, atrial fibrillation with controlled ventricular rate not
included

- CTCAE grade ≥ 2 peripheral vascular disease (at least brief < 24 hrs) episodes
of ischemia managed non-surgically and without permanent deficit

- Patients who have received prior therapy with an anthracycline (including doxorubicin
or liposomal doxorubicin) must have an echocardiogram assessment and are excluded if
the ejection fraction < 50%

- No known hypersensitivity to any of the components of fosbretabulin tromethamine or
bevacizumab

- No clinical symptoms or signs of gastrointestinal obstruction or requirement
parenteral hydration and/or nutrition; patients with bowel involvement on CT scan

- No patients with medical history or conditions not otherwise previously specified
that, in the opinion of the investigator, should exclude participation in this study

- No concurrent drugs known to prolong the QTc interval, including anti-arrhythmic
medications

- Recovered from the effects of recent surgery, radiotherapy, or chemotherapy

- At least 1 week since any hormonal therapy directed at the malignant tumor

- At least 3 weeks since any other prior therapy directed to the malignant tumor,
including chemotherapy or biological/targeted and immunologic agents (including small
molecules and murine monoclonal antibodies)

- At least 12 weeks since prior chimeric or human or humanized monoclonal antibodies
(including bevacizumab) or VEGF-receptor fusion protein (including VEGF
Trap/aflibercept)

- At least 4 weeks since prior radiotherapy

- More than 30 days since prior investigational therapy

- Patients are allowed to receive, but are not required to receive, 2 additional
cytotoxic regimens for management of recurrent or persistent disease, with no more
than 1 non-platinum, non-taxane regimen allowed

- No prior fosbretabulin tromethamine or any other vascular-disrupting agent (VDA)

- No prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for
the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the
past 3 years

- Prior radiotherapy for localized cancer of the breast, head and neck, or skin is
permitted, provided that it was completed more than 3 years prior to
registration

- No prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment
of ovarian, fallopian tube or primary peritoneal cancer within the past 3 years

- Prior adjuvant chemotherapy for localized breast cancer allowed provided it was
completed more than 3 years prior to registration

- No prior cancer treatment that contraindicates this protocol therapy

- No major surgery within the past 28 days and no anticipation of need for major
surgery procedures during the course of the study

- No core biopsy within the past 7 days