Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Sirolimus

Temsirolimus

MTOR Inhibitors

Tablets, orally administered, twice daily

AZD8055

Ian Smith

Tomohide Tamura

The primary objective is to assess the safety and tolerability of AZD8055 in Japanese patients with advanced solid tumours.

Study to Assess the Safety and Tolerability of the Tor Kinase Inhibitor AZD8055

A Phase I, Open Label, Single-centre Study to Assess the Safety and Tolerability of the Tor Kinase Inhibitor AZD8055 Administered Orally to Japanese Patients With Advanced Solid Tumours

AstraZeneca

Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Glioblastoma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

Katherine E Warren, M.D.

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....

Background:

* 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.

Objectives:

* 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.

Eligibility:

-Patients with histologically proven glioma are eligible for this study. Patients should have failed prior standard treatment with radiotherapy.

Design:

* 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.

AZD8055 for Adults With Recurrent Gliomas

Phase I Trial of AZD8055, An Oral MTOR Kinase Inhibitor, for Adults With Recurrent Gliomas

National Cancer Institute (NCI)

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Oral tablet, single dose on Day 1, followed by a 48 hour - 7 day washout and then either twice daily alternate days dosing from multiple dose day 1 onwards or twice daily dosing for 21 days from multiple dose day 1 onwards followed by 7 days no treatment. Cycles of 28 days.

Ian Smith, MD

To investigate the safety and tolerability of AZD8055 intermittent dosing schedules when given orally to patients with advanced solid malignancies and lymphomas. Two intermittent dosing schedules will be explored with increasing doses until a maximum tolerated dose is determined for each schedule.

Preliminary Anti-tumour Activity of mTor Kinase Inhibitor in Advanced Tumours

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of the m-Tor Kinase Inhibitor AZD8055 Using Intermittent Dosing Schedules in Patients With Advanced Solid Malignancies and Lymphomas

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Assess the Safety and Tolerability of the Tor Kinase Inhibitor AZD8055	NCT00973076	Cancer Solid Tumors Advanced Solid ...	AZD8055	20 Years -	AstraZeneca
AZD8055 for Adults With Recurrent Gliomas	NCT01316809	Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig... Malignant Gliom... Brainstem Gliom...	AZD8055	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Preliminary Anti-tumour Activity of mTor Kinase Inhibitor in Advanced Tumours	NCT01194193	Cancer Advanced Solid ... Lymphomas	AZD8055	18 Years -	AstraZeneca

Spots Global Cancer Trial Database for azd8055

Every month we try and update this database with for azd8055 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azd8055

Every month we try and update this database with for azd8055 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azd8055 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.