Bevacizumab and Irinotecan or Temozolomide in Treating Patients With Recurrent or Refractory Glioblastoma Multiforme or Gliosarcoma
Condition: Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm
MeSH terms: Glioblastoma; Gliosarcoma; Brain Neoplasms; Recurrence
Intervention: Bevacizumab; Irinotecan Hydrochloride; Temozolomide
Intervention description: Given IV; Given IV; Given orally
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Irinotecan; Temozolomide; Camptothecin; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying the side effects and how well giving bevacizumab
      together with irinotecan or temozolomide works in treating patients with recurrent or
      refractory glioblastoma multiforme or gliosarcoma. 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 may also stop the growth of tumor cells by blocking blood
      flow to the tumor. Drugs used in chemotherapy, such as irinotecan and temozolomide, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Giving bevacizumab together with irinotecan or temozolomide may kill more
      tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma

               -  Original histology of low-grade glioma with subsequent histological diagnosis of
                  GBM or gliosarcoma allowed

          -  Recurrent or refractory disease, meeting all of the following criteria:

               -  Must have received prior temozolomide

               -  Pathologic or imaging confirmation of tumor progression or regrowth required

                    -  Confirmation of true progressive disease (rather than radiation necrosis) by
                       positron emission tomography, thallium scanning, MRI spectroscopy, or
                       surgical documentation required for patients who received prior interstitial
                       brachytherapy, Gliadel wafer, or stereotactic radiosurgery

          -  Unequivocal radiographic evidence of tumor progression by MRI within the past 14 days
             (while on a stable dose of steroids for ? 5 days)

          -  No acute intratumoral hemorrhage on MRI

               -  Patients with MRI demonstrating old hemorrhage or subacute blood after a
                  neurosurgical procedure (biopsy or resection) are eligible

          -  Karnofsky performance status 70-100%

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for at least 6 months
             after completion of bevacizumab therapy

          -  Systolic blood pressure ? 160 mm Hg or diastolic blood pressure ? 90 mm Hg
             (antihypertensive medication allowed)

          -  Able to undergo brain MRI scans with intravenous gadolinium

          -  Absolute neutrophil count ? 1,500 cells/mm?

          -  Platelet count ? 100,000 cells/mm?

          -  Hemoglobin ? 10 g/dL (transfusion or other intervention allowed)

          -  WBC ? 3,000 cells/mm?

          -  AST < 2 times upper limit of normal

          -  Bilirubin ? 1.6 mg/dL

          -  Creatinine < 1.5 mg/dL

          -  Urine protein:creatinine ratio ? 0.5 by urinalysis OR total urinary protein < 1,000 mg
             by 24-hour urine collection

          -  INR < 1.4 (for patients not on warfarin)

          -  No patients with severely impaired renal function (i.e., estimated glomerular
             filtration rate < 30 mL/min or on dialysis)

          -  No other prior invasive malignancy, except nonmelanomatous skin cancer or carcinoma in
             situ of the cervix, unless the patient has been disease free and off therapy for that
             disease for ? 3 years

          -  No severe, active comorbidity, defined as any of the following:

               -  Transmural myocardial infarction or unstable angina within the past 6 months

               -  Evidence of recent myocardial infarction or ischemia manifested as ST elevation
                  of ? 2 mm by EKG performed within the past 14 days

               -  New York Heart Association class II-IV congestive heart failure requiring
                  hospitalization within the past 12 months

               -  History of stroke or transient ischemic attack within the past 6 months

               -  Cerebrovascular accident within the past 6 months

               -  Serious and inadequately controlled cardiac arrhythmia

               -  Significant vascular disease (e.g., aortic aneurysm or history of aortic
                  dissection)

               -  Clinically significant peripheral vascular disease

               -  Evidence of bleeding diathesis or coagulopathy

               -  Serious or nonhealing wound, ulcer, or bone fracture

               -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
                  within the past 28 days

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of study entry

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within the past 14 days

               -  Acquired immune deficiency syndrome (AIDS)

          -  No significant traumatic injury within the past 28 days

          -  No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract
             disease resulting in an inability to take oral medication; requirement for IV
             alimentation; prior surgical procedures affecting absorption; or active peptic ulcer
             disease)

          -  No disease that would obscure toxicity or dangerously alter drug metabolism

          -  No concurrent major surgical procedures

          -  Recovered from prior therapy

          -  Recent resection of recurrent or progressive tumor allowed provided the following
             criteria are met:

               -  Failed prior radiotherapy that was completed ? 42 days ago

               -  Residual disease after resection of recurrent glioblastoma is not mandated

          -  More than 28 days since prior surgery or open biopsy

          -  More than 7 days since prior core or needle biopsy

          -  At least 28 days since prior investigational agents

          -  At least 14 days since prior vincristine

          -  At least 42 days since prior nitrosoureas

          -  At least 21 days since prior procarbazine

          -  At least 28 days since other prior cytotoxic therapy

          -  At least 7 days since prior noncytotoxic agents (e.g., interferon, tamoxifen,
             thalidomide, or isotretinoin [except radiosensitizers])

          -  At least 14 days since prior enzyme-inducing antiepileptic drugs (EIAEDs)

               -  Concurrent non-hepatic EIAEDs allowed

          -  No other concurrent CYP3A4 inducers, such as rifampin or Hypericum perforatum (St.
             John's wort)

          -  Concurrent full-dose anticoagulants (e.g., warfarin or low molecular weight heparin)
             allowed provided all of the following criteria are met:

               -  No active bleeding or pathological condition that carries a high risk of bleeding
                  (e.g., tumor involving major vessels or known varices)

               -  In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulants or
                  on a stable dose of low molecular weight heparin

          -  No concurrent highly active antiretroviral therapy

          -  No concurrent prophylactic use of growth factors