RO4929097and Bevacizumab in Treating Patients With Progressive or Recurrent Malignant Glioma

Stopped early · Phase 1/Phase 2

Conditions studied: Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

In brief

This phase I/II trial is studying the side effects and the best dose of RO4929097 to see how well it works when given together with bevacizumab compared to bevacizumab alone in treating patients with progressive or recurrent malignant glioma. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving RO4929097 together with bevacizumab may kill more tumor cells.

Key facts

Study ID

NCT01189240

Run by

National Cancer Institute (NCI)

People needed

13

Starts

2010-12-01

Expected to finish

2015-02-01

Last updated by the study team

2015-12-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically confirmed malignant glioma (phase I)
• Glioblastoma
• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Mixed anaplastic oligoastrocytoma
• Histologically confirmed glioblastoma following radiotherapy and temozolomide (phase II)
• Progressive or recurrent disease after conformal external-beam radiation therapy and concurrent temozolomide, followed by ≥ 1 adjuvant course of temozolomide
• Measurable disease by MRI within the past 2 weeks
• Tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of malignant glioma completed and signed by a pathologist
• Karnofsky performance status 60-100%
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Urine protein: If proteinuria ≥ +2 protein, a protein level should be < 1,000 mg by a 24-hour urine collection
• Electrolytes (calcium, chloride, magnesium, potassium, phosphorus, sodium) within institutional normal limits
• Fertile patients must use 2 forms of effective contraception before, during, and for ≥ 12 months (6 months phase II, bevacizumab arm only) after treatment
• Negative pregnancy test
• Not pregnant or nursing
• At least 5 years since prior malignancy except nonmelanoma skin cancer, or carcinoma in situ of the cervix, breast, or bladder
• Mini Mental State Exam score of ≥ 15
• Must be able to tolerate MRI

You may not qualify if…

• No serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive the treatment outline in this protocol with reasonable safety
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to gamma-secretase inhibitor RO4929097 or bevacizumab
• Must be able to swallow capsules
• No malabsorption syndrome or other condition that would interfere with intestinal absorption
• No baseline QTcF > 450 msec (male) or QTcF > 470 msec (female)
• Not history of being serologically positive for hepatitis A, B, or C
• No history of cirrhosis
• No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia despite adequate electrolyte supplementation
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• A history of torsades de pointes or other significant cardiac arrhythmias other than chronic, stable atrial fibrillation
• Psychiatric illness and/or social situations that would limit compliance with study requirements
• No serious or non-healing wound, ulcer, or bone fracture
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
• No clinically significant cardiovascular disease, including any of the following:
• Inadequately controlled hypertension (systolic BP > 160 mm Hg and/or diastolic BP > 90 mm Hg) despite antihypertensive medication
• History of cerebrovascular accident or transient ischemic attack at any time
• Myocardial infarction or unstable angina within the past 12 months
• NYHA grade II-IV congestive heart failure
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
• Clinically significant peripheral vascular disease

Where it is running

• University of California at Los Angeles (UCLA ) — Los Angeles, California, United States
• University of California San Francisco Medical Center-Parnassus — San Francisco, California, United States
• H. Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States
• Memorial Sloan-Kettering Cancer Center — New York, New York, United States

Full record on ClinicalTrials.gov

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