Amgen 386 for Recurrent Glioblastoma

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma, GBM, Brain Tumor, Glioma Read More

Inclusion Criteria

• Signed informed consent approved by the Institutional Review Board prior to participant entry
• Age ≥ 18 years.
• Karnofsky ≥ 70%
• Participant must be able and willing to comply with study and/or follow-up procedures Participants must have histologically confirmed diagnosis of GBM patients with either grade III or IV malignant glioma are eligible to the Phase I portion of the study) and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bidimensional product of enhancement, a new enhancing lesion, or significant increase in T2 FLAIR) following prior therapy (i.e. chemotherapy, XRT, other investigational therapies).
• No more than 2 prior episodes of progressive disease (patients with more than 2 prior episodes of progressive disease are eligible for the Cohort B, Phase I portion of this study)
• An interval of at least 4 weeks (to start of study agent) between prior surgical resection or one week from stereotactic biopsy
• An interval of at least 12 weeks (to start of study agent) from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is histological confirmation of unequivocal tumor progression
• From the projected start of scheduled study treatment, the following time periods must have relapsed: 4 weeks (or 5 half lives, whichever is shorter) from any investigational agent, 4 weeks (or 5 half lives, whichever is shorter) from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (or 5 half lives, whichever is shorter), or 4 weeks (or 5 half lives, whichever is shorter) from other anti-tumor therapies.
• Participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide, and alopecia).
• No evidence of hemorrhage on the baseline MRI or CT scan other than those that are ≤ grade 1 and either post-operative or stable on at least two consecutive scans. Clinical Labs - performed within 14 days prior to enrollment
• Hematocrit ≥ 29%, ANC ≥ 1,000 cells/μl, platelets ≥ 100,000 cells/μl ;
• Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of normal;
• PTT or aPTT ≤ 1.5 times upper limit of normal and INR ≤ 1.5
• Calculated creatinine clearance ≥ 40 mL/min according to the Cockcroft-Gault formula OR per 24 hour urine collection
• Urinary protein quantitative value of < 30 mg/dL in urinalysis or <1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample;
• Participants of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use an accepted and highly effective non-hormonal method of contraception (i.e. double barrier method [e.g., condom plus diaphragm]) from signing the informed consent through 6 months after last dose of study drug.

Exclusion Criteria:

• Prior anti-angiogenic therapy targeting VEGF or VEGF receptor including prior bevacizumab.
• Prior AMG 386 therapy or other molecules that inhibit the angiopoietins or Tie2 receptor.
• Co-medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids.
• Active infection requiring intravenous antibiotics
• Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine and tacrolimus.
• Current us of warfarin sodium or any other Coumadin-derivative anticoagulant. Participant must be off Coumadin-derivative anticoagulants for at least seven days prior to starting study drug. ow molecular weight heparin is allowed.
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than supportive care or epidemiologic studies.
• Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng. Participants should stop using any herbal medications 7 days prior to first dose of study drug.
• History of clinically significant bleeding within 6 months of enrollment
• History of allergic reactions to bacterially produced proteins
• Known hypersensitivity to any component of bevacizumab (cohort B only)
• Known sensitivity to any of the products to be administered during dosing
• History of venous or arterial thromboembolism within 12 months prior to enrollment.
• Severe hepatic insufficiency (ongoing grade 3 or greater hepatic adverse events) or known active chronic hepatitis.
• Inadequately controlled hypertension (defined as systolic blood pressure >140 and/or diastolic blood pressure > 90 mmHg). The use of anti-hypertensive medications to control hypertension is permitted.
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent.
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
• Serious, non-healing wound, ulcer (including gastrointestinal), or bone fracture.
• Any condition which in the investigator's opinion makes the subject unsuitable for study participation.
• Pregnant (positive pregnancy test) or lactating. Refusal or inability to use highly effective means of contraception (men and women) in participants of child-bearing potential.