AZD8055 for Adults With Recurrent Gliomas

NCT01316809 | Completed Phase 1

• 2 other identifiers: 11012211-C-0122
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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....

Conditions

Glioblastoma Multiforme; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Malignant Glioma; Brainstem Glioma

Keywords

Brain; Tumor; Recurrent; Surgery; Radiation; Glioma; Brain Tumor; Glioblastoma Multiforme; Astrocytoma; Brainstem Glioma

Outcome Measures

Primary Outcomes (2)

• 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).

  2 years

• Generate pharmacokinetic data of AZD8055 on a continuous once daily schedule

  2 years

Secondary Outcomes (1)

• To obtain exploratory information about the antitumor activity of AZD8055.

  2 years

Study Arms (2)

A

EXPERIMENTAL

Surgical arm

Drug: AZD8055

B

EXPERIMENTAL

Non-surgical arm

Drug: AZD8055

Interventions

AZD8055 DRUG

Patients will start at 120 mg once daily

A; B

Eligibility Criteria

• Age: 18 Years - 99 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. These include glioblastoma (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), and malignant glioma/astrocytoma NOS. Additionally, patients with progressive low-grade gliomas and patients with infiltrative brainstem gliomas, diagnosed radiographically rather than by biopsy, will be eligible.
• 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 for the non-surgical arm 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.
• All patients or their previously designated DPA (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) must sign an informed consent indicating that they are aware of the investigational nature of this study.
• Patients must be greater than or equal to 18 years old, and must have a life expectancy \> 8 weeks.
• 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 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.
• 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.

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)

• 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

• Salazar OM, Rubin P, Feldstein ML, Pizzutiello R. High dose radiation therapy in the treatment of malignant gliomas: final report. Int J Radiat Oncol Biol Phys. 1979 Oct;5(10):1733-40. doi: 10.1016/0360-3016(79)90554-6. No abstract available.

  PMID: 231023 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Oligodendroglioma; Glioma; Neoplasms; Recurrence; Brain Neoplasms

Interventions

(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Katherine E Warren, 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: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 16, 2011
• Study Start: March 4, 2011
• Primary Completion: April 14, 2014
• Study Completion: April 4, 2016
• Last Updated: December 12, 2019

Record last verified: 2016-04-14

Locations

US (1)