AZD8055 for Adults With Recurrent Gliomas
- AZD8055 is an experimental cancer treatment drug that works by inhibiting a protein called mTOR, which is known to promote tumor cell and blood vessel growth and to control tumor s energy and nutrient levels. AZD8055 is the first drug that inhibits both types of mTOR protein and is expected to be more effective than prior mTOR inhibitors. However, more research is needed to determine its safety and effectiveness in treating brain tumors known as gliomas that have not responded to standard treatments.
- To evaluate the safety and effectiveness of AZD8055 in individuals with gliomas that have not responded to standard treatments.
- Individuals at least 18 years of age who have been diagnosed with gliomas that have not responded to standard chemotherapy, surgery, or radiation.
- Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies.
- Participants will be separated into two treatment groups: one group that will receive surgery to remove the glioma and one that will not have surgical treatment.
- Participants in the nonsurgical treatment group will take AZD8055 by mouth daily for a 42-day cycle of treatment. Participants will keep a diary to record doses and keep track of any side effects.
- Participants in the surgical treatment group will take AZD8055 by mouth daily for 7 days, and then will have tumor removal surgery. At least 3 weeks after surgery, participants will resume doses of AZD8055 and will continue to take the drug for as long as the tumor does not recur.
- During treatment, participants will have regular visits to the clinical center, involving frequent blood and urine tests and other examinations to monitor the effects of treatment. Participants will have imaging studies to study the cancer's response to the treatment.
- Participants will continue to have cycles of treatment for as long as the treatment continues to be effective and the side effects are not severe enough to stop participation in the study....
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of AZD8055, An Oral MTOR Kinase Inhibitor, for Adults With Recurrent Gliomas|
- To establish the maximum tolerated dose (MTD) of AZD8055 on a continuous once daily schedule in patients with recurrent gliomas not on enzyme-inducing anti-epileptic drugs (EIAED). [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Generate pharmacokinetic data of AZD8055 on a continuous once daily schedule [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To obtain exploratory information about the antitumor activity of AZD8055. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2011|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Patients will start at 120 mg once daily
Patients will start at 120 mg once daily
- Recurrent glioma patients have very limited treatment options. A significant percentage of gliomas have increased activity of the PI3K/Akt/mTOR pathway, mostly due to loss of PTEN.
- AZD8055 is a first in-class inhibitor of the kinase activity of mTOR, specifically inhibiting both mTORC1 and mTORC2 complexes. Preclinical data generated in the Neuro-Oncology Branch Laboratory of Dr. Howard Fine demonstrated that AZD8055 has significant anti-glioma activity in vivo and in vitro.
- To establish the maximally tolerated dose (MTD) of continuous once daily AZD8055 in patients with recurrent malignant gliomas not on enzyme-inducing anti-epileptic drugs (EIAED).
- To generate pharmacokinetic data on continuous once daily AZD8055 dosing.
-Patients with histologically proven glioma are eligible for this study. Patients should have failed prior standard treatment with radiotherapy.
- This study will accrue up to 24 evaluable patients (non-surgical arm). Cohorts of 3 or 6 patients will receive continuous AZD8055 once daily orally for 42 days. The MTD will be based on the tolerability observed during the first 6 weeks of treatment only. Up to three patients may be enrolled simultaneously at each dose level. The dose of AZD8055 can be progressively escalated if only 0/3 or 1/6 patients experience a dose limiting toxicity at the prior dose level.
- A subset of patients in whom tumor re-resection is considered standard of care will receive 1-week treatment with AZD8055 and then undergo resection. Patients will be treated at the highest dose level shown to be safe at the time of enrollment. Once patients recover from surgery, they will restart treatment with AZD8055 and stay on treatment as long as there is no tumor progression or protocol-mandated removal criteria. Management of toxicity will be the same as non-surgical patients receiving their second and subsequent cycles of therapy as delineated in the protocol. Up to 12 patients will enter the surgical arm of this trial.
- The accrual ceiling will be open to 42 patients to factor in replacing those who come off
treatment prior to cycle 1.
-At the end of Cycle 1, patients in both treatment arms (surgical and non-surgical) may choose to continue to receive AZD8055 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01316809
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Katherine E Warren, M.D.||National Cancer Institute (NCI)|