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Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00621686
Recruitment Status : Completed
First Posted : February 22, 2008
Results First Posted : January 4, 2017
Last Update Posted : May 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE February 21, 2008
First Posted Date  ICMJE February 22, 2008
Results First Submitted Date  ICMJE November 7, 2016
Results First Posted Date  ICMJE January 4, 2017
Last Update Posted Date May 8, 2018
Actual Study Start Date  ICMJE September 2008
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
6-month Progression-free Survival [ Time Frame: at 6 months ]
Primary Endpoint: 6-month progression free survival (PFS6): The proportion of successes will be estimated using the binomial point estimator (number of successes divided by the total number of evaluable patients) and the binomial 95% confidence interval estimated. To be classified as a success, an evaluable patient must be alive and progression-free 6 months after registration to the study. Patients who die prior to 6 months after study registration will be considered to have failed. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions compared to pretreatment MRI and/or CT scan.
Original Primary Outcome Measures  ICMJE
 (submitted: February 21, 2008)
  • 6-month Progression-free Survival
  • Safety, toxicity, and adverse events
Change History Complete list of historical versions of study NCT00621686 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
  • Time to Progression [ Time Frame: Time from study registration to a) date of disease progression, or b) last follow-up; Up to 15 years ]
    Time to progression (TTP) is defined to be the length of time from study registration to a) date of disease progression as defined by section 11.0 of the protocol, or b) last follow-up. If a patient dies without documentation of disease progression, the patient will be considered to have had a tumor progression at the time of death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Time to progression curves were compared via the log-rank test. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions compared to pretreatment MRI and/or CT scan.
  • Overall Survival [ Time Frame: Time from date of registration to a) date of death due to any cause or b) last follow-up; Up to 15 years ]
    Overall survival (OS) is defined as the length of time from date of registration to a) date of death due to any cause or b) last follow-up.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2008)
  • Time to Progression
  • Overall Survival
  • Quality of life as assessed by the FACT-Br at baseline, prior to every other treatment course, and at the end of treatment
  • Utility of dynamic contrast-enhanced MRI as a predictor of response
  • Relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme
Official Title  ICMJE Phase II Trial of Bevacizumab in Combination With Sorafenib in Recurrent Glioblastoma Multiforme
Brief Summary

RATIONALE: 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. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with sorafenib may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab together with sorafenib works in treating patients with recurrent glioblastoma multiforme.

Detailed Description

OBJECTIVES:

Primary

  • Identify the clinical efficacy of bevacizumab and sorafenib, as measured by 6-month progression-free survival, in patients with recurrent glioblastoma multiforme.

Secondary

  • Assess time to progression of this patient population.
  • Assess overall survival of this patient population.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib once daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and plasma sample collection at baseline and then periodically during study treatment for translational research studies. Translational research studies include analysis of circulating endothelial cells and circulating endothelial progenitor cells by flow cytometry and measurement of angiogenic proteins in plasma by ELISA. DNA and buffy coat are extracted and collected from the blood samples for pharmacogenetic studies.

Quality of life is assessed at baseline, prior to every other treatment course, and at the end of treatment.

After completion of study treatment, patients are followed at 28-42 days, every 3 months for 5 years, and then annually for 10 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • Biological: bevacizumab
  • Drug: sorafenib tosylate
Study Arms  ICMJE
  • Experimental: Sorafenib + Bevacizumab/Group A

    Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.

    Patients undergo blood and plasma sample collection at baseline and then periodically during study treatment for translational research studies. Translational research studies include analysis of circulating endothelial cells and circulating endothelial progenitor cells by flow cytometry and measurement of angiogenic proteins in plasma by ELISA. DNA and buffy coat are extracted and collected from the blood samples for pharmacogenetic studies.

    Quality of life is assessed at baseline, prior to every other treatment course, and at the end of treatment.

    After completion of study treatment, patients are followed at 28-42 days, every 3 months for 5 years, and then annually for 10 years.

    Interventions:
    • Biological: bevacizumab
    • Drug: sorafenib tosylate
  • Experimental: Sorafenib + Bevacizumab /Group B

    Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.

    Patients undergo blood and plasma sample collection at baseline and then periodically during study treatment for translational research studies. Translational research studies include analysis of circulating endothelial cells and circulating endothelial progenitor cells by flow cytometry and measurement of angiogenic proteins in plasma by ELISA. DNA and buffy coat are extracted and collected from the blood samples for pharmacogenetic studies.

    Quality of life is assessed at baseline, prior to every other treatment course, and at the end of treatment.

    After completion of study treatment, patients are followed at 28-42 days, every 3 months for 5 years, and then annually for 10 years.

    Interventions:
    • Biological: bevacizumab
    • Drug: sorafenib tosylate
Publications * Galanis E, Jaeckle KA, Anderson S, et al.: NCCTG phase II trial of bevacizumab in combination with sorafenib in recurrent GBM. [Abstract] J Clin Oncol 28 (Suppl 15): A-2018, 2010.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 7, 2016)
54
Original Enrollment  ICMJE
 (submitted: February 21, 2008)
53
Actual Study Completion Date  ICMJE February 19, 2014
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed glioblastoma multiforme as determined by pre-registration central pathology review

    • Gliosarcoma allowed
  • Must have evidence of tumor progression by MRI or CT scan following radiotherapy or the most recent anti-tumor therapy
  • No more than 1 chemotherapy regimen for progressive or recurrent disease
  • Bidimensionally measurable or evaluable disease by MRI or CT scan
  • No evidence of CNS hemorrhage on baseline CT or MRI

    • Patients with T1 hyperintensity confined to the surgical cavity which is felt likely due to post surgical blood contaminating the intracavity cerebrospinal fluid or irrigation that have not yet absorbed and which is not felt to clinically or radiographically represent new spontaneous hemorrhage are eligible
    • Patients with old blood products or hemosiderin without a history of spontaneous bleeding are eligible

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin > 9.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal
  • AST ≤ 3 times upper limit of normal
  • Creatinine ≤ upper limit of normal
  • Urine protein:creatinine ratio < 1 OR urine protein < 1,000 mg by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for six months after completion of study treatment
  • Able to complete questionnaire(s) alone or with assistance
  • Willing to return to NCCTG enrolling institution for follow-up
  • Willing to provide mandatory blood samples for research purposes
  • Not immunocompromised (other than that related to the use of corticosteroids)
  • No known HIV positivity
  • No concurrent uncontrolled illness including, but not limited to, the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • No inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg while on antihypertensive medications)

    • Patients with well-controlled hypertension are eligible
  • No myocardial infarction or unstable angina within the past 6 months
  • No congestive heart failure requiring the use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • No New York Heart Association class II-IV congestive heart failure
  • No significant vascular disease (e.g., aortic aneurysm or aortic dissection)
  • No peripheral arterial thrombosis within the past 6 months
  • No stroke or transient ischemic attack within the past 6 months
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation)
  • No active or recent history of hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past 30 days
  • No serious, nonhealing wounds, ulcers, or bone fractures
  • No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation)
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No significant traumatic injury within the past 28 days
  • No known hypersensitivity to any of the components of sorafenib or bevacizumab
  • No other active malignancy within the past 3 years, except nonmelanoma skin cancer or carcinoma in situ of the cervix

    • Patients with a history of prior malignancy must not be receiving specific treatment (other than hormonal therapy) for that malignancy
  • No co-morbid systemic illness or other concurrent severe disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or significantly interfere with the proper assessment of safety and toxicity of the prescribed study regimen

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 12 weeks since prior radiotherapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • More than 2 weeks since prior small molecule cell cycle inhibitors
  • At least 1 week since prior fixed-dose corticosteroids (or no corticosteroids)
  • No prior intratumoral chemotherapy, stereotactic radiosurgery or interstitial brachytherapy unless there is a separate lesion on MRI that is not part of the prior treatment field OR there is proof of recurrent disease based on biopsy, MRI spectroscopy, or PET scan
  • No prior antiangiogenic therapy
  • No prior surgical procedures affecting absorption
  • More than 7 days since prior core biopsy or other minor surgical procedures

    • Placement of a vascular access device is allowed
  • More than 28 days since prior major surgical procedure or open biopsy
  • No concurrent major surgical procedure
  • No other concurrent investigational agents
  • No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, fosphenytoin, carbamazepine, phenobarbital, or primidone)
  • No other concurrent potent CYP3A4 inducers (e.g., rifampin or St. John's wort)
  • No concurrent therapeutic anticoagulation with warfarin

    • Prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided the INR < 1.5
    • Therapeutic anticoagulation with low molecular weight heparin allowed
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00621686
Other Study ID Numbers  ICMJE NCCTG-N0776
NCI-2009-00832 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000587614 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Evanthia Galanis, MD Mayo Clinic
PRS Account Alliance for Clinical Trials in Oncology
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP