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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


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer

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Trial Information

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


PRIMARY OBJECTIVES:

I. To estimate the progression-free survival hazard ratio of the combination of bevacizumab
and fosbretabulin tromethamine (CA4P) compared to bevacizumab alone in patients with
persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.

SECONDARY OBJECTIVES:

I. To determine the nature and degree of toxicity of fosbretabulin tromethamine plus
bevacizumab.

II. To characterize and compare progression-free survival in patients with measurable
disease (RECIST criteria) and patients with detectable (non-measurable) disease between
regimens.

III. To determine the overall survival for both regimens. IV. To estimate the proportion of
patients with measurable disease who have objective tumor responses by treatment.

V. To provide descriptive information about CA-125 responses by regimen and where possible
by objective tumor responses.

OUTLINE: This is a multicenter study. Patients are stratified according to measurable
disease status (measurable vs non-measurable or detectable disease), prior bevacizumab
therapy (no vs yes), and most recent platinum-free interval (more than 12 months vs 6-12
months vs less than or equal to 6 months). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab IV over 30-90 minutes and fosbretabulin tromethamine IV
over 10-20 minutes on day 1. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab as in arm I. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Bradley Monk

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02666

NCT ID:

NCT01305213

Start Date:

March 2011

Completion Date:

Related Keywords:

  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Hartford HospitalHartford, Connecticut  06102-5037
Franklin Square Hospital CenterBaltimore, Maryland  21237
Northeast Georgia Medical CenterGainesville, Georgia  30501
Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Indiana University Medical CenterIndianapolis, Indiana  46202
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
Memorial Health University Medical CenterSavannah, Georgia  31404
University of CincinnatiCincinnati, Ohio  45267-0502
Sutter General HospitalSacramento, California  95816
Sanford Cancer Center-Oncology ClinicSioux Falls, South Dakota  57104
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's HospitalGreen Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent HospitalGreen Bay, Wisconsin  54301-3526
Bay Area Medical CenterMarinette, Wisconsin  54143
Moores University of California San Diego Cancer CenterLA Jolla, California  92093
University of Michigan University HospitalAnn Arbor, Michigan  48109
Holy Family Memorial HospitalManitowoc, Wisconsin  54221
Saint Dominic-Jackson Memorial HospitalJackson, Mississippi  39216
Summa Akron City HospitalAkron, Ohio  44304
Gynecologic Oncology GroupPhiladelphia, Pennsylvania  19103
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134