Title A Phase II Evaluation of TRC105 in the treatment of recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy)
IRB CASE 1312
Hospital Main Campus
Phase Phase 2
- Determine median overall survival in patients with recurrent or progressive GBM who have progressed on bevacizumab.
- Assess safety and tolerability of TRC105 when given with bevacizumab by CTCAE version 4.0.
- Determine objective response rate (ORR) by modified RANO criteria.
- Determine the rate of progression free survival at 6 months (PFS-6).
- Determine median time to progression.
- Explore associations between clinical outcome and soluble angiogenic biomarkers including but not limited to VEGF, PDGF and TGF-B
- Patients with histologically confirmed glioblastoma or other grade IV malignant glioma (i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam fractionated radiotherapy and temozolomide chemotherapy.
- Patients with documented radiographic progression following bevacizumab therapy for treatment of glioblastoma or other grade IV malignant glioma (the patient must be on bevacizumab at the time of last progression).
- Patients with up to 3 prior recurrences are allowed.
- Karnofsky performance status ≥ 70%.
- Age ≥ 18 years old.
- Patients must have the following laboratory values:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- Hemoglobin (Hgb) > 9 g/dL
- Serum total bilirubin: ≤ 1.5 x ULN
- ALT and AST ≤ 3.0 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Blood coagulation parameters: INR ≤ 1.5
- Minimum interval since completion of radiation treatment is 12 weeks.
- Minimum interval since last drug therapy:
- 2 weeks since last non-cytotoxic therapy
- 3 weeks must have elapsed since the completion of a non-nitrosourea-containing chemotherapy regimen
- 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen.
- Patients must have signed an approved informed consent and authorization permitting release of personal health information.
- Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant. Female patients of child-bearing potential must have a negative pregnancy test.
- Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ three years.
- Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment and/or for at least 5 days before starting treatment.
- Patients must have a Mini Mental State Exam score ≥ 15.
- Patients who have had previous treatment with TRC105.
- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
- Patients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias
- Clinically significant resting bradycardia
- Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
- Uncontrolled hypertension (defined by a SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg while on anti-hypertensive medications)
- Patients with cirrhosis, or active viral or nonviral hepatitis.
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
- Pregnant or breast-feeding women
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human, chimeric, or humanized antibodies.
- Patients with active bleeding or pathologic conditions that carry a high risk of bleeding, (i.e. hereditary hemorrhagic telangiectasia).
- Patients who are currently receiving anticoagulation treatment
- Patients unwilling or unable to comply with the protocol