This is a study of two investigational drugs called onartuzumab and bevacizumab that are being tested alone or in combination with each other for the treatment of a specific type of brain tumor called glioblastoma.
- Conditions
- Patients with recurrent GlioblastomaMedDRA 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)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-005912-27-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 129
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
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 × 109/L; platelet count < 100 × 109/L; or hemoglobin (Hb) < 9.0 g/dL within 7 days prior to enrollment Note: The use of transfusion or other intervention to achieve Hb = 9 g/dL is acceptable.
4. Total bilirubin = 1.5 × ULN (except in patients diagnosed with Gilbert’s disease)
5. AST (SGOT), ALT (SGPT), or alkaline phosphatase (ALP) = 2.5 ×ULN
6. Serum creatinine > 1.5 × ULN or calculated creatinine clearance
(CrCl) < 60 mL/min (Cockcroft and Gault)
7. Urine dipstick test for proteinuria = 2+ Patients found to have = 2+ proteinuria should undergo a 24-hour urine collection and must demonstrate = 1.0 g of protein in 24 hours)
8. International normalized ratio (INR), protohrombin time (PT), or activated partial thromboplastin time (APTT) as follows:
In the absence of therapeutic intent to anticoagulate the patient:
INR > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method