AZD7451 for Recurrent Gliomas

NCT01468324 | Completed Phase 1

• 2 other identifiers: 12000512-C-0005
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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....

Conditions

Glioblastoma Multiforme

Keywords

Brain; Angiogenesis; Radiotherapy; Malignant; Tumor; Glioma; Glioblastoma Multiforme; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• 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).

  3 years

Secondary Outcomes (1)

• To obain exploratory information about the anti-tumor activity of AZD7451.

  3 years

Interventions

AZD7451 DRUG

Depending on dose level, AZD7451 will be given once daily for 28 day cycles.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically proven malignant primary gliomas who have progressive disease after radiotherapy will be eligible for this protocol.
• Patients must have an MRI scan performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI is required.
• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
• Patients will be eligible four weeks after surgery if they have recovered from the effects of surgery.
• Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease postoperatively, an MRI should be done:
• no later than 96 hours in the immediate post-operative period or
• at least 4 weeks post-operatively, and
• within 14 days of registration, and
• on a stable steroid dosage for at least 5 days.
• If the 96 hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required on a stable steroid dosage for at least 5 days.
• Patients must have failed prior radiation therapy.
• Ability of subject or Legally Authorized Representative (LAR) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study.
• Patients must be greater than or equal to18 years old, and must have a life expectancy \> 8 weeks. Because no dosing or adverse event data are currently available on the use of AZD7451 in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• Patients must have a Karnofsky performance status of greater than or equal to 60
• Patients must be at least 4 weeks from radiation therapy. Additionally, patients must be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine, 2 weeks from vincristine and 2 weeks from last bevacizumab administration. Patients must be at least 4 weeks from other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen) including investigative agents. With the exception of alopecia, all toxicities from prior therapies should be resolved to CTCAE less than or equal to grade 1.

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 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Scanlon PW, Taylor WF. Radiotherapy of intracranial astrocytomas: analysis of 417 cases treated from 1960 through 1969. Neurosurgery. 1979 Sep;5(3):301-8.

  PMID: 228216 BACKGROUND

• FRANKEL SA, GERMAN WJ. Glioblastoma multiforme; review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment. J Neurosurg. 1958 Sep;15(5):489-503. doi: 10.3171/jns.1958.15.5.0489. No abstract available.

  PMID: 13576192 BACKGROUND

• Bloom HJ. Combined modality therapy for intracranial tumors. Cancer. 1975 Jan;35(1):111-20. doi: 10.1002/1097-0142(197501)35:13.0.co;2-#.

  PMID: 162849 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Neoplasms; Glioma; Brain Neoplasms

Interventions

AZD7451

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Teri N Kreisl, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 5, 2011
• First Posted: November 9, 2011
• Study Start: October 5, 2011
• Primary Completion: April 23, 2014
• Study Completion: April 23, 2014
• Last Updated: December 17, 2019

Record last verified: 2014-04-22

Locations

US (1)