AZD7451 for Recurrent Gliomas
- AZD7451 is a drug that may help interfere with brain tumor cell growth. It can prevent glioma cells from entering into normal brain tissue, and slow or stop the growth of additional tumors. Researchers want to see if AZD7451 is effective against gliomas that have not responded to surgery, radiation, or chemotherapy.
- To see if AZD7451 is a safe and effective treatment for gliomas that have not responded to standard treatments.
- Individuals at least 18 years of age who have gliomas that have not responded to standard treatments.
- Participants will be screened with a physical exam, medical history, blood and urine tests, heart function tests, an eye exam, and imaging studies.
- Participants will take AZD7451 daily by mouth for 28-day cycles of treatment.
- Participants will keep a medication diary and record any side effects. Treatment will be monitored with frequent blood tests and imaging studies.
- Treatment will continue as long as there are no serious side effects and the tumor does not start growing again....
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of AZD7451, A Topomysin-Receptor Kinase (TRK) Inhibitor, For Adults With Recurrent Glioblastoma Multiforme (GBM)|
- To establish the maximum tolerated dose of AZD7451 on a continuous once daily schedule in patients with recurrent gliomas not on enzyme-inducing anti-epileptic drugs (EIAED). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To obain exploratory information about the anti-tumor activity of AZD7451. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2011|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Recurrent glioma patients have very limited treatment options. A major cause of gliomarelated morbidity and mortality is the extensive infiltrative and invasive nature of glioma cells. Thus, inhibition of glioma invasion is a potentially promising strategy.
Work in the Neuro-Oncology Branch laboratory of Dr. Howard Fine has identified TrkA as an important signaling receptor for mediating glioma cell invasion. Both genetic and pharmacological inhibition of Trk potently inhibits glioma invasion and tumor progression in vitro and in vivo. AZD7451 is a first in-class inhibitor of Trk.
To establish the maximally tolerated dose (MTD) of continuous twice a day AZD7451 dosing in patients with recurrent glioblastoma not on enzyme-inducing anti-epileptic drugs (EIAED).
To generate pharmacokinetic data on continuous twice a day AZD7451 dosing.
Patients with histologically proven glioblastoma are eligible for this study. Patients should have failed prior standard treatment with radiotherapy.
This study will accrue up to 60 evaluable patients. Cohorts of 3 to 6 patients will receive continuous AZD7451 twice a day orally for 28 days. The MTD will be based on the tolerability observed during the first 4 weeks of treatment only. Up to three patients may be enrolled simultaneously at each dose level. The dose of AZD7451 can be progressively escalated if only 0/3 or 1/6 patients experience a dose limiting toxicity at the prior dose level.
At the end of Cycle 1, patients may choose to continue to receive AZD7451 until disease progression or until they experience unmanageable drug related toxicity, as long as they are continuing to derive clinical benefit and do not fulfill any of the criteria for removal from protocol therapy. Each cycle during this extension period will last 28 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468324
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Teri N Kreisl, M.D.||National Cancer Institute (NCI)|