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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01305213
First received: February 25, 2011
Last updated: April 16, 2014
Last verified: December 2013
  Purpose

This randomized phase II trial is studying how well giving bevacizumab with or without fosbretabulin tromethamine works in treating patients with ovarian epithelial, fallopian tube, or peritoneal cavity cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to 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 when given together with fosbretabulin tromethamine in treating ovarian, fallopian tube, and peritoneal cavity cancer.


Condition Intervention Phase
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Biological: bevacizumab
Drug: fosbretabulin tromethamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events as assessed by CTCAE v 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    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.

  • Measurable disease by RECIST criteria and PFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Objective tumor response in patients with measurable disease [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The effects of treatment on the proportion responding by RECIST will be examined.

  • Response by CA-125 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The effects of treatment on the proportion responding by CA125 will be examined.


Estimated Enrollment: 110
Study Start Date: March 2011
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: fosbretabulin tromethamine
Given IV
Other Names:
  • CA4P
  • combretastatin A4 phosphate
  • Zybrestat
Experimental: Arm II (bevacizumab)
Patients receive bevacizumab as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

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 (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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01305213

  Show 30 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Bradley Monk Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01305213     History of Changes
Other Study ID Numbers: NCI-2011-02666, NCI-2011-02666, CDR0000696220, GOG-0186I, GOG-0186I, U10CA027469
Study First Received: February 25, 2011
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Abdominal Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Antibodies
Antibodies, Monoclonal
Combretastatin
Combretastatin A-4
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on April 21, 2014