AZD7451 for Recurrent Gliomas

Completed · Phase 1

Conditions studied: Glioblastoma Multiforme

In brief

Background: \- 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. Objectives: \- To see if AZD7451 is a safe and effective treatment for gliomas that have not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have gliomas that have not responded to standard treatments. Design: * 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....

Key facts

Study ID

NCT01468324

Run by

National Cancer Institute (NCI)

People needed

14

Starts

2011-10-05

Expected to finish

2014-04-23

Last updated by the study team

2019-12-17

Who can join

Age: 18 and older, up to 100. 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.
• 2 Prior treatment with AZD7451.
• History of hypersensitivity to active metabolites or excipients of AZD7451.
• 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, Appendix I) classification of heart disease >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 criterion; 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. Continuous or intermittent atrial fibrillation requiring treatment. 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 excluded if QTc is greater than or equal to 460 msec.
• Any concurrent medication that may cause QTc prolongation or induce
• Torsades de Pointes 1) Drugs listed in Appendix H, Table 2, that in the investigator s opinion cannot be discontinued are allowed; however, must be monitored closely.
• Concomitant medications that are moderate or potent inducers or inhibitors of CYP3A4 are not permitted within the specified wash-out periods prior to or during treatment with AZD7451
• Patients with a history of corneal disease such as corneal ulcers, corneal dystrophies, keratoconus.
• Refractory nausea and vomiting or significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of AZD7451, including the ability to swallow the oral solution.
• Patients known to have active hepatitis B or C (testing 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.
• Pregnant women are excluded from this study because AZD7451 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD7451, breastfeeding should be discontinued if the mother is treated with AZD7451. Female patients must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Patients known to have a malignancy (other than their malignant glioblastoma) 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.
• Patients known to be HIV-positive (testing is not required for entry on study) and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD7451. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

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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