Bevacizumab With or Without Fosbretabulin Tromethamine in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

NCT ID: NCT01305213

Last Updated: 2019-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-21
• Study Completion Date: 2016-11-03

Brief Summary

This randomized phase II trial studies how well bevacizumab with or without fosbretabulin tromethamine works in treating patients with ovarian epithelial, fallopian tube, or peritoneal cavity cancer that has come back or is persistent. Monoclonal antibodies, such as bevacizumab, find tumor cells and help kill them. Bevacizumab and fosbretabulin tromethamine may stop the growth of ovarian cancer by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective with or without fosbretabulin tromethamine in treating ovarian epithelial, fallopian tube, and peritoneal cavity cancer.

Detailed Description

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 (Response Evaluation Criteria in Solid Tumors [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 cancer antigen (CA)-125 responses by regimen and where possible by objective tumor responses.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: 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.

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

Conditions

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (bevacizumab)

Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Arm II (bevacizumab, fosbretabulin tromethamine)

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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Fosbretabulin Tromethamine

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Bevacizumab

Given IV

Intervention Type: BIOLOGICAL

Fosbretabulin Tromethamine

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Avastin; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar FKB238; Bevacizumab Biosimilar HD204; Bevacizumab Biosimilar HLX04; Bevacizumab Biosimilar IBI305; Bevacizumab Biosimilar LY01008; Bevacizumab Biosimilar MIL60; Bevacizumab Biosimilar QL 1101; Bevacizumab Biosimilar SCT501; HD204; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; SCT501; CA4P; Zybrestat

Eligibility Criteria

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 computed tomography (CT) scan, magnetic resonance imaging (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 or MRI
• Detectable disease in a patient is defined as one who does not have measurable disease but has at least one of the following conditions:

• Baseline values of CA-125 at least 2 x upper limit of normal (ULN)
• 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
• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase 3 protocol or rare tumor protocol for the same patient population
• Patients who have had one prior treatment must have a performance status of 0, 1, or 2
• Patients who have had two or three prior treatments must have a performance status of 0 or 1
• Patients should be free of acute hepatitis and active infection requiring parenteral antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
• Recovery from the effects of recent surgery, radiotherapy, or chemotherapy

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
• Any other prior therapy directed at the malignant tumor, including chemotherapy, biological/targeted and immunologic agents, must be discontinued at least 3 weeks prior to registration (including small molecules and murine monoclonal antibodies); chimeric or human or humanized monoclonal antibodies (including bevacizumab) or vascular endothelial growth factor (VEGF) receptor fusion protein (including VEGF Trap/aflibercept) must be discontinued for at least 12 weeks prior to registration; no investigational therapy within 30 days prior to the first date of study treatment
• Any prior radiation therapy must be discontinued at least 4 weeks prior to registration
• 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 (adenosine diphosphate [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)
• 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

• Definitions:

• Platinum-free interval (PFI) is the period of time from the date of last platinum therapy to the date of progression (recurrence by CA-125, CT, etc.; CT is preferred) of disease or initiation of subsequent therapy (whichever occurs first); non-platinum maintenance therapy (e.g., extending taxane treatment) is excluded as a ?subsequent therapy;? if the patient?s last regimen used platinum, and she has NOT progressed before enrolling onto this study, then her PFI will be calculated from the date of last platinum therapy to the date of registration onto this study
• 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?
• ANC greater than or equal to 1,500/mcl
• Platelets greater than or equal to 100,000/mcl
• Hemoglobin greater than or equal to 9 g/dL
• Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)
• Potassium within the normal reference range for the laboratory; correction with supplements is acceptable
• Magnesium within the normal reference range for the laboratory; correction with supplements is acceptable
• Calcium within the normal reference range for the laboratory; correction with supplements is acceptable
• Bilirubin less than or equal to 1.5 x ULN
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< less than or equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 x ULN
• Urine protein should be screened by urine analysis; 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) for patient enrollment
• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception
• Patients must have signed an approved informed consent and authorization permitting the release of personal health information
• Patients must meet pre-entry requirements

Exclusion Criteria

• Patients who have received prior fosbretabulin tromethamine or any other vascular disrupting agent (VDA)
• Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted below, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received 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 last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 90 days prior to the first date of study treatment
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of treatment on this study
• Patients with clinically significant cardiovascular disease; this includes:

• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg despite antihypertensive medications
• History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 60 beats per minute [bpm]), heart block (excluding 1st degree block being, PR interval prolongation only), congenital long QT syndrome, new ST segment elevation or depression, or new Q waves on electrocardiogram (ECG)
• Patients with corrected QT interval (QTc) > 470 msec
• Requirement for receiving any drug known to prolong the QTc interval, including anti-arrhythmic medications; 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
• New York Heart Association (NYHA) class II or greater congestive heart failure
• Serious cardiac arrhythmia requiring medication; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
• Patients who have received prior treatment with an anthracycline (including doxorubicin and or pegylated liposomal doxorubicin [Doxil; PLD]) must have an echocardiogram assessment and are excluded if they have an ejection fraction < 50%
• Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral vascular disease (at least brief [< 24 hrs] episodes of ischemia managed non-surgically and without permanent deficit)
• Known hypersensitivity to any of the components of fosbretabulin tromethamine or bevacizumab
• Major surgery within 28 days prior to the first date of study treatment
• Anticipation of need for major surgical procedures during the course of the study
• Core biopsy within 7 days prior to the first date of study treatment
• Patients with clinical symptoms or signs of gastrointestinal obstruction and patients who require parenteral hydration and/or nutrition; patients with bowel involvement on CT scan
• Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study; the investigator can consult the Study Chair or Study Co-Chairs for uncertainty in this regard
• Patients who are pregnant or nursing

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NRG Oncology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bradley J Monk

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

John Muir Medical Center-Concord Campus

Concord, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, United States

SCL Health Lutheran Medical Center

Wheat Ridge, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Mercy Hospital

Miami, Florida, United States

Northeast Georgia Medical Center-Gainesville

Gainesville, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Sudarshan K Sharma MD Limited-Gynecologic Oncology

Hinsdale, Illinois, United States

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Maine Medical Center-Bramhall Campus

Portland, Maine, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

Baltimore, Maryland, United States

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

Saint Dominic-Jackson Memorial Hospital

Jackson, Mississippi, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Women's Cancer Center of Nevada

Las Vegas, Nevada, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

University of Cincinnati/Barrett Cancer Center

Cincinnati, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Green Bay Oncology at Saint Vincent Hospital

Green Bay, Wisconsin, United States

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, United States

Holy Family Memorial Hospital

Manitowoc, Wisconsin, United States

Bay Area Medical Center

Marinette, Wisconsin, United States

Countries

United States

References

Monk BJ, Sill MW, Walker JL, Darus CJ, Sutton G, Tewari KS, Martin LP, Schilder JM, Coleman RL, Balkissoon J, Aghajanian C. Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol. 2016 Jul 1;34(19):2279-86. doi: 10.1200/JCO.2015.65.8153. Epub 2016 May 23.

Reference Type: DERIVED

PMID: 27217446 (View on PubMed)

Other Identifiers

NCI-2011-02666

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000696220

Identifier Type: -

Identifier Source: secondary_id

GOG-0186I

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0186I

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02666

Identifier Type: -

Identifier Source: org_study_id