Recurrent Fallopian Tube CarcinomaPhase 2NCT01305213
Bevacizumab With or Without Fosbretabulin Tromethamine in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer
A Phase 2 study testing Bevacizumab, Fosbretabulin Tromethamine and Laboratory Biomarker Analysis in people with Recurrent Fallopian Tube Carcinoma and Recurrent Ovarian Carcinoma, run by National Cancer Institute (NCI) at 51 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
- What is being tested?
- Bevacizumab, Fosbretabulin Tromethamine and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 51 sitesUnited States
- Study dates
- 21 Mar 2011to 3 Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
51 sites in 1 country.
51 sites in 1 country
United States51 sites
Summa Akron City Hospital/Cooper Cancer Center
Akron, Ohio, 44304
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, 91505
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
University of Cincinnati/Barrett Cancer Center
Cincinnati, Ohio, 45219
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907
John Muir Medical Center-Concord Campus
Concord, California, 94520
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218
Duke University Medical Center
Durham, North Carolina, 27710
Northeast Georgia Medical Center-Gainesville
Gainesville, Georgia, 30501
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, 54301-3526
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, 54303
Greenville Health System Cancer Institute-Eastside
Greenville, South Carolina, 29615
Hartford Hospital
Hartford, Connecticut, 06102
Sudarshan K Sharma MD Limited-Gynecologic Oncology
Hinsdale, Illinois, 60521
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Saint Dominic-Jackson Memorial Hospital
Jackson, Mississippi, 39216
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Borgess Medical Center
Kalamazoo, Michigan, 49048
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Women's Cancer Center of Nevada
Las Vegas, Nevada, 89169
Beebe Medical Center
Lewes, Delaware, 19958
Cedars Sinai Medical Center
Los Angeles, California, 90048
Holy Family Memorial Hospital
Manitowoc, Wisconsin, 54221
Bay Area Medical Center
Marinette, Wisconsin, 54143
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124
Mercy Hospital
Miami, Florida, 33133
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Saint Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Maine Medical Center-Bramhall Campus
Portland, Maine, 04102
Women and Infants Hospital
Providence, Rhode Island, 02905
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
Sutter Medical Center Sacramento
Sacramento, California, 95816
Memorial Health University Medical Center
Savannah, Georgia, 31404
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Washington University School of Medicine
St Louis, Missouri, 63110
SCL Health Lutheran Medical Center
Wheat Ridge, Colorado, 80033
University of Massachusetts Memorial Health Care
Worcester, Massachusetts, 01605
About this study
Official title: A Randomized Phase II Evaluation of Single-Agent Bevacizumab (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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Being tested
- Bevacizumab, Fosbretabulin Tromethamine, Laboratory Biomarker Analysis
- Medical subject headings
- Fallopian Tube Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabBiological
Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin
Given IV
Fosbretabulin TromethamineDrug
Also called CA4P, Zybrestat
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Bevacizumab; Other: 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. Receives: Biological: Bevacizumab; Drug: Fosbretabulin Tromethamine; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Toxicities will be characterized by their frequency and severity. Differences in the level of toxicities by treatment regimen will be assessed by classifying them as severe or not severe and examining the relative proportion of severe toxicities.
Measured: Up to 5 years
Measurable Disease by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and Progression Free Survival (PFS)
Differences between measurable versus non-measurable disease status on PFS and OS will be examined with plots of survival curves, estimates of quartiles and hazard ratios.
Measured: Up to 5 years
Tumor Response
Complete and Partial Tumor Response by RECIST 1.0
Measured: 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)
Differences between measurable versus non-measurable disease status on PFS and OS will be examined with plots of survival curves, estimates of quartiles and hazard ratios.
Measured: Up to 5 years
Response by CA-125
The effects of treatment on the proportion responding by CA125 will be examined.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2011 (estimated)
- Study start21 Mar 2011
- Primary completion20 Aug 2016
- Study completion3 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Fallopian Tube CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- NRG Oncology
- Responsible party
- Sponsor
- Investigators
- Bradley J Monk, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01305213
- Sponsor's protocol ID
- NCI-2011-02666
- Other IDs
- NCI-2011-02666, CDR0000696220, GOG-0186I, GOG-0186I, U10CA180868, U10CA027469
- Status last verified
- Jul 2019
- First submitted
- 25 Feb 2011
- Last updated
- 30 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27217446
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Evaluation of Single-Agent Bevacizumab (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
- ClinicalTrials.gov ID
- NCT01305213
- Acronym / sponsor ID
- NCI-2011-02666
- Conditions
- Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Collaborators
- NRG Oncology
- Study start
- 21 Mar 2011 (actual)
- Primary completion
- 20 Aug 2016 (actual)
- Study completion
- 3 Nov 2016 (actual)
- First posted
- 28 Feb 2011 (estimated)
- Results
- Posted 12 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (bevacizumab) | Active comparator | Biological: Bevacizumab, Other: Laboratory Biomarker AnalysisPatients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| Arm II (bevacizumab, fosbretabulin tromethamine) | Experimental | Biological: Bevacizumab, Drug: Fosbretabulin Tromethamine, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- 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:
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, AvastinGiven IV | Biological | Arm I (bevacizumab), Arm II (bevacizumab, fosbretabulin tromethamine) |
| Fosbretabulin TromethamineAlso: CA4P, ZybrestatGiven IV | Drug | Arm II (bevacizumab, fosbretabulin tromethamine) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (bevacizumab), Arm II (bevacizumab, fosbretabulin tromethamine) |
Primary outcome
Progression-free Survival (PFS)
Time frame: 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
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.
5 secondary outcomes
Incidence of Adverse Events (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0
Time frame: Up to 5 years
Measurable Disease by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria and Progression Free Survival (PFS)
Time frame: Up to 5 years
Tumor Response
Time frame: 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)
Time frame: Up to 5 years
Response by CA-125
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27217446Monk 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bradley J Monk principal investigator
NRG Oncology
51 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Fosbretabulin Tromethamine and Laboratory Biomarker Analysis in people with Recurrent Fallopian Tube Carcinoma and Recurrent Ovarian Carcinoma, run by National Cancer Institute (NCI) at 51 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 41 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 51 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01305213, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.