NCT01305213

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
107

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Mar 2011

Longer than P75 for phase_2

Geographic Reach
1 country

51 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 25, 2011

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 28, 2011

Completed
21 days until next milestone

Study Start

First participant enrolled

March 21, 2011

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 20, 2016

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 3, 2016

Completed
8 months until next milestone

Results Posted

Study results publicly available

July 12, 2017

Completed
Last Updated

July 30, 2019

Status Verified

July 1, 2019

Enrollment Period

5.4 years

First QC Date

February 25, 2011

Results QC Date

June 14, 2017

Last Update Submit

July 17, 2019

Conditions

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS)

    The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored.

    For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 21 day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, up to 5 years

Secondary Outcomes (5)

  • Incidence of Adverse Events (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0

    Up to 5 years

  • Measurable Disease by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and Progression Free Survival (PFS)

    Up to 5 years

  • Tumor Response

    for those patients whose disease can be evaluated by physical examination, response wa assessed prior to each 21 day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, up to 5 years

  • Overall Survival (OS)

    Up to 5 years

  • Response by CA-125

    Up to 5 years

Study Arms (2)

Arm I (bevacizumab)

ACTIVE COMPARATOR

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.

Biological: BevacizumabOther: Laboratory Biomarker Analysis

Arm II (bevacizumab, fosbretabulin tromethamine)

EXPERIMENTAL

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.

Biological: BevacizumabDrug: Fosbretabulin TromethamineOther: Laboratory Biomarker Analysis

Interventions

BevacizumabBIOLOGICAL

Given IV

Also known as: 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
Arm I (bevacizumab)Arm II (bevacizumab, fosbretabulin tromethamine)

Given IV

Also known as: CA4P, Zybrestat
Arm II (bevacizumab, fosbretabulin tromethamine)

Correlative studies

Arm I (bevacizumab)Arm II (bevacizumab, fosbretabulin tromethamine)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +26 more criteria

You may not qualify if:

  • 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
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (51)

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

John Muir Medical Center-Concord Campus

Concord, California, 94520, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sutter Medical Center Sacramento

Sacramento, California, 95816, United States

Location

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, 80907, United States

Location

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, 80218, United States

Location

SCL Health Lutheran Medical Center

Wheat Ridge, Colorado, 80033, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

Mercy Hospital

Miami, Florida, 33133, United States

Location

Northeast Georgia Medical Center-Gainesville

Gainesville, Georgia, 30501, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Sudarshan K Sharma MD Limited-Gynecologic Oncology

Hinsdale, Illinois, 60521, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Maine Medical Center-Bramhall Campus

Portland, Maine, 04102, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

Baltimore, Maryland, 21237, United States

Location

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, 01605, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49048, United States

Location

Saint Dominic-Jackson Memorial Hospital

Jackson, Mississippi, 39216, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Women's Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

University of Cincinnati/Barrett Cancer Center

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, 44124, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, 29615, United States

Location

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Green Bay Oncology at Saint Vincent Hospital

Green Bay, Wisconsin, 54301-3526, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, 54303, United States

Location

Holy Family Memorial Hospital

Manitowoc, Wisconsin, 54221, United States

Location

Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Fallopian Tube NeoplasmsOvarian Neoplasms

Interventions

BevacizumabImmunoglobulin GDisulfides

Condition Hierarchy (Ancestors)

Genital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFallopian Tube DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesEndocrine Gland NeoplasmsOvarian DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsImmunoglobulin IsotypesSulfidesAnionsIonsElectrolytesInorganic ChemicalsHydrogen SulfideSulfur CompoundsOrganic Chemicals

Results Point of Contact

Title
Linda Gedeon for Michael Sill, PhD
Organization
NRG Oncology

Study Officials

  • Bradley J Monk

    NRG Oncology

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 25, 2011

First Posted

February 28, 2011

Study Start

March 21, 2011

Primary Completion

August 20, 2016

Study Completion

November 3, 2016

Last Updated

July 30, 2019

Results First Posted

July 12, 2017

Record last verified: 2019-07

Locations