Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme | NCT00621686 | Trialant

Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme | NCT00621686 | Trialant

Official Title: 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.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Eligibility Criteria: 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