AZD8055 for Adults With Recurrent Gliomas

Completed · Phase 1

Conditions studied: Glioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Malignant Glioma, Brainstem Glioma

In brief

Background: \- 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. Objectives: \- To evaluate the safety and effectiveness of AZD8055 in individuals with gliomas that have not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with gliomas that have not responded to standard chemotherapy, surgery, or radiation. Design: * 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....

Key facts

Study ID: NCT01316809
Run by: National Cancer Institute (NCI)
People needed: 22
Starts: 2011-03-04
Expected to finish: 2016-04-04
Last updated by the study team: 2019-12-12

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients who, in the view of the treating physician, have significant active hepatic, renal, pulmonary or psychiatric diseases are ineligible.
Prior treatment with AZD8055 or AZD2014.
History of hypersensitivity to active or excipients of AZD8055 or drugs with a similar chemical structure or class to AZD8055.
Clinically significant cardiovascular event (e.g. myocardial infarction, angina pectoris, coronary artery bypass graft, angioplasty, vascular stent, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease greater than or equal to 2 within 6 months before entry; or presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
Hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criteria; patients with history of prior intratumoral bleeding, however, need to undergo a non-contrast head CT to exclude acute blood.
Ventricular arrhythmias requiring continuous therapy or asymptomatic sustained ventricular tachycardia within 12 months before study entry. Atrial fibrillation, controlled on medication is not excluded. Patients with significant ECG abnormalities such as complete left bundle block and third degree heart block are not eligible.
QTc prolongation with other medications that required discontinuation of that medication.
Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
QTc with Bazett s correction that is unmeasurable, or >470 msec on screening ECG. (Note: If a subject has a QTc interval >470 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be less than or equal to 470 msec in order for the subject to be eligible for the study. Patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is greater than or equal to 460 msec.
Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes Drugs, that in the investigator s opinion cannot be discontinued are allowed; however, must be monitored closely.
Concomitant medications that are moderate or potent inducers of CYP3A4 or CYP2C8 function (with the exception of dexamethasone) are not permitted within the specified wash-out periods prior to or during treatment with AZD8055.
Patients with uncontrolled hypercholesterolemia or hypertriglyceridemia (fasting state) despite lipid-lowering therapy.
Patients with manifest diabetes mellitus type 1 and patients with uncontrolled diabetes mellitus type 2 or corticosteroid-induced hyperglycemia despite optimal therapy.
Refractory nausea and vomiting or significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of AZD8055, including the ability to swallow the tablet whole.
Patients known to have active hepatitis B or C or HIV on anti-retrovirals (testing is not required for entry on study).
Other concomitant anti-cancer therapy except corticosteroids.
Patients with a peripheral neuropathy CTCAE > 1 in the prior 4 weeks or active muscle diseases (including dermatomyositis, polymyositis, inclusion body myositis, muscular dystrophy and metabolic myopathy) or family history of myopathy.
Patients with pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis.
Evidence of active infection or active bleeding diatheses.
Patients with an abnormal LVEF on echocardiogram at baseline.
Women who are currently pregnant or breast feeding.
Patients known to have a malignancy (other than their malignant glioma) that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except for non-melanoma skin cancer, carcinoma in situ in the cervix or ductal carcinoma in situ).
Major surgery within 4 weeks or incompletely healed surgical incision before starting therapy.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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