Clinical Trials Logo

Clinical Trial 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....


Clinical Trial Description

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. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01316809
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase Phase 1
Start date March 4, 2011
Completion date April 4, 2016

See also
  Status Clinical Trial Phase
Active, not recruiting NCT05023551 - Study of DSP-0390 in Patients With Recurrent High-Grade Glioma Early Phase 1
Recruiting NCT06059690 - Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells Phase 1/Phase 2
Recruiting NCT04116411 - A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients Phase 2
Terminated NCT01902771 - Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors Phase 1
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Completed NCT00038493 - Temozolomide and SCH66336 for Recurrent Glioblastoma Multiforme Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Recruiting NCT01923922 - CT Perfusion in the Prognostication of Cerebral High Grade Glioma N/A
Completed NCT01956734 - Virus DNX2401 and Temozolomide in Recurrent Glioblastoma Phase 1
Suspended NCT01386710 - Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma Phase 1/Phase 2
Completed NCT01301430 - Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme. Phase 1/Phase 2
Completed NCT01402063 - PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation Phase 2
Active, not recruiting NCT00995007 - A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas Phase 2
Terminated NCT00990496 - A Study Using Allogenic-Cytomegalovirus (CMV) Specific Cells for Glioblastoma Multiforme (GBM) Phase 1
Terminated NCT01044966 - A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma Phase 1/Phase 2
Completed NCT00402116 - Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients Phase 1/Phase 2
Completed NCT00112502 - Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme Phase 2
Completed NCT00504660 - 6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients Phase 2
Recruiting NCT05366179 - Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc Phase 1