Patients with recurrent Glioblastoma MedDRA version: 14.1 Level: LLT Classification code 10006153 Term: Brain tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed glioblastoma at first recurrence after concurrent or adjuvant chemoradiotherapy A local pathology report constitutes adequate documentation of histology for study inclusion. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be glioblastoma. 2. Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria A minimum of 12 weeks must have elapsed from the completion of radiotherapy to randomization to minimize the potential for magnetic resonance imaging (MRI) changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling. 3. Prior treatment with TMZ 4. No more than one prior line of chemotherapy Concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with an investigational agent, is considered one line of chemotherapy. 5. No prior treatment with bevacizumab or other VEGF- or VEGF-receptor-targeted agent 6. No prior exposure to experimental treatment targeting either the HGF or Met pathway 7. Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field 8. No prior treatment with prolifeprospan 20 with carmustine wafer 9. No prior intracerebral agent Recovery from the toxic effects of prior therapy, with a minimum time of: a) = 28 days elasped from the administration of any investigational agent b) = 28 days elapsed from the administration of any prior cytotoxic agents, except = 14 days from vincristine, = 21 days from procarbazine, and = 42 days from nitrosureas c) = 7 days elapsed from administration of any non-cytotoxic agent (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid) 11. Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: a) Surgery must have confirmed the recurrence. b) A minimum of 28 days must have elapsed from the day of surgery to randomization. For core or needle biopsy, a minimum of 7 days must have elapsed prior to randomization. c) Craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization. 12. No evidence of recent hemorrhage on baseline MRI of the brain However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, or presence of punctuate hemorrhage in the tumor are eligible. 13. No need for urgent palliative intervention for primary disease (e.g., impending herniation) 14. Availability of formalin-fixed paraffin-embedded tumor tissue representative of glioblastoma 15. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator 16. Age = 18 years 17. Karnofsky performance status = 70% 18. Stable or decreasing dose of corticosteroids within 5 days prior to randomization 19. For women who are not postmenopausal (i.e., < 2 years after last menstruation) or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: agreement to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier
Exclusion criteria
Exclusion criteria: 1. Patients unable to undergo brain MRI scans with IV gadolinium 2. Pregnancy or lactation (or a positive pregnancy test within 7 days before starting any component of study medication) 3. Absolute neutrophil count (ANC) 1.5 × ULN or calculated creatinine clearance (CrCl) 1.5 or PT > 1.5 × ULN or aPTT > 1.5 ×ULN OR In the presence of therapeutic intent to anticoagulate the patient: INR or PT and aPTT not within therapeutic limits (according to the medical standard in the institution) or patient has not been on a stable dose of anticoagulants for at least 2 weeks before randomization. (Note: Per ASCO guidelines, low-molecular-weight heparin [LMWH] should be the preferred approach.) 9. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg while on antihypertensive medication) 10. Uncontrolled diabetes, as evidenced by fasting serum glucose level > 200 mg/dL 11. Prior history of hypertensive crisis or hypertensive encephalopathy 12. New York Heart Association (NYHA) Grade II or greater congestive cardiac failure 13. History of myocardial infarction (within 12 months) or unstable angina (within 6 months) prior to randomization 14. History of stroke or transient ischemic attacks within 6 months prior to randomization 15. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization 16. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation) 17. History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization 18. History of intracranial abscess within 6 months prior to randomization 19. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization 20. Anticipation of need for major surgical procedure during the course of the trial 21. Serious non-healing wound, active ulcer, or untreated bone fracture 22. History of another malignancy in the previous 3 years, with a disease-free interval of < 3 years Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. 23. Evidence of any active infection requiring hospitalization or IV antibiotics within 2 weeks prior to randomization 24. Known hypersensitivity to any excipients of onartuzumab or bevacizumab 25. Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibody
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of onartuzumab + bevacizumab relative to placebo + bevacizumab as measured by investigator-assessed progression-free survival (PFS) • To evaluate the efficacy of onartuzumab + bevacizumab relative to placebo + bevacizumab as measured by investigator-assessed PFS in the subgroup of patients with Met-positive (Met+) glioblastoma;Secondary Objective: • To evaluate the efficacy of onartuzumab + bevacizumab relative to placebo + bevacizumab as measured by overall survival (OS) rate at 9 months (OS-9) and OS overall, in all patients and in those with Met+ glioblastoma • To evaluate the efficacy of onartuzumab + bevacizumab relative to placebo + bevacizumab as measured by PFS rate at 6-months (PFS-6), objective response rate (ORR), and duration of response (DOR) in all patients and in those with Met+ tumors;Primary end point(s): • Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Patients will be followed until the point at which approximately 84 investigator-assessed PFS events are observed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS) OS-9 PFS-6 Objective Response Rate (ORR) Duration of Objective Response (DOR);Timepoint(s) of evaluation of this end point: Follow-up for survival will continue until all patients have either died, or are lost to follow-up, or the Sponsor decides to end the trial, whichever occurs first. | — |
Countries
Canada, France, Germany, Italy, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
Outcome results
None listed