mTORC1/mTORC2 Kinase Inhibitor AZD2014 in Previously Treated Glioblastoma Multiforme

NCT02619864 | Completed Phase 1 DMC

• 1 other identifier: I222
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

The standard or usual treatment for this disease is standard chemotherapy alone. AZD2014 is a new type of drug for glioblastoma multiforme. In the laboratory it has been shown to slow the growth of glioblastoma multiforme. In some animal studies AZD2014 seemed to work better when given with a drug called temozolomide.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RP2D) of AZD2014

  Day 0

Secondary Outcomes (3)

• Number and severity of adverse events

  30 months

• Response rate per RANO criteria

  30 months

• To evaluate the plasma levels of AZD2014 alone at the time of resection

  30 months

Study Arms (1)

AZD2014 plus temozolomide

EXPERIMENTAL

Patients will receive single agent AZD2014 for 2 days immediately prior to surgery at a fixed dose of 125 mg bid po (i.e. on days -2, -1, and on morning of day 0 \[day of surgery\]). After recovery from surgery, patients will start the dose escalation (within 7-21 days after tumour resection).

Drug: AZD2014

Interventions

AZD2014 DRUG

AZD2014 plus temozolomide

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed glioblastoma multiforme that is recurrent after primary treatment (surgery/radiation/temozolomide) (i.e. first progression). Patients may not have had disease progression while receiving adjuvant temozolomide or radiation.
• All patients must have an available formalin fixed paraffin embedded tissue block (from their primary tumour) and must have provided informed consent for the release of the block. Patients participating in the pharmacodynamics study must have provided consent for release of a representative sample of the resected tumour.
• Presence of clinically and/or radiologically documented disease. MRI scan must be performed within 14 days prior to registration.
• All patients enrolled to DL3 and the dose expansion cohort at RP2D must have measurable disease according to RANO criteria as follows: At least one enhancing lesion which is ≥ 10 mm x 10 mm
• Patients must be ≥18 years of age.
• Patients must have an ECOG performance status of 0 or 1.
• Patients must have received one prior temozolomide regimen, discontinued at least 16 weeks prior to registration. Patients may have received one other cytotoxic regimen (for example CCNU).
• Patients may not have received immunotherapies, biologic and viral therapies, angiogenesis inhibitors, mTOR, or PARP inhibitors
• Patients must have recovered from all reversible toxicity related to prior chemotherapy and have adequate washout from prior chemotherapy, and investigational agents as follows: longest of one of the following:
• two weeks,
• standard cycle length of prior regimen,
• half-lives for investigational drugs.
• Prior external beam radiation must have been completed at least 4 weeks prior to registration.
• Previous surgery is permitted provided that a minimum of 21 days have elapsed between any major surgery (excluding resection for patients participating in the Pharmacodynamic Study) and date of registration, and that wound healing has occurred.
• Patients must have recovered from any treatment related toxicities prior to registration (unless grade 1, irreversible, or considered by investigator as not clinically significant).

You may not qualify if:

• Patients who have undergone any of the following procedures or experienced conditions currently or in the preceding 12 months:
• Coronary artery bypass graft
• Angioplasty
• Vascular stent
• Myocardial infarction (MI)
• Angina pectoris
• Congestive heart failure New York Heart Association (NYHA) Grade 2
• Ventricular arrhythmias requiring continuous therapy
• Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled.
• Hemorrhagic or thrombotic stroke, including transient ischemic attacks or any other central nervous system bleeding
• Patients with a baseline LVEF ≤ 50% by MUGA scan, and ≤ 55% by ECHO.
• Patients with mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome or unexplained sudden death under 40 years of age.
• Any evidence of severe or uncontrolled systemic disease, active infection (including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or a prior history of tuberculosis), active bleeding or bleeding diathesis or renal diseases such as nephritis or renal tubular acidosis.
• Patients with history of pre-existing and/or clinically or radiologically active interstitial lung disease.
• History of hypersensitivity to protocol therapy or any excipient used in this study

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (4)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Lapointe S, Mason W, MacNeil M, Harlos C, Tsang R, Sederias J, Luchman HA, Weiss S, Rossiter JP, Tu D, Seymour L, Smoragiewicz M. A phase I study of vistusertib (dual mTORC1/2 inhibitor) in patients with previously treated glioblastoma multiforme: a CCTG study. Invest New Drugs. 2020 Aug;38(4):1137-1144. doi: 10.1007/s10637-019-00875-4. Epub 2019 Nov 9.

  PMID: 31707687 RESULT

MeSH Terms

Conditions

Glioblastoma

Interventions

vistusertib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Warren Mason

  Univ. Health Network-OCI/Princess Margaret Hospital, Toronto ON

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2015
• First Posted: December 2, 2015
• Study Start: December 22, 2016
• Primary Completion: March 22, 2019
• Study Completion: February 25, 2020
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)