Vistusertib (AZD2014) For Recurrent Grade II-III Meningiomas

NCT03071874 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: 16-563R01CA201130-01A1
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying a chemotherapy as a possible treatment for Meningiomas (recurrent). The study intervention involved in this study is:

• -AZD2014 (vistusertib)

Conditions

Meningioma

Keywords

Meningioma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  proportion of patients alive and without progression

  6 months

Secondary Outcomes (4)

• Overall Survival

  2 years

• Radiographic Response Rate

  2 years

• Duration of Radiographic Response

  2 years

• Frequency of Adverse Events

  2 years

Study Arms (1)

AZD2014

EXPERIMENTAL

* AZD2014 will be administered orally at a pre-determine dose * Twice daily for two consecutive days out of every seven days * Cycles will last 28 days

Drug: AZD2014

Interventions

AZD2014 DRUG

AZD2014 is a dual mTORC1/mTORC2 inhibitor

Also known as: vistusertib

AZD2014

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed intracranial meningioma, grade II-III,that has recurred or progressed at previous treatment.
• Participants must be willing and able to undergo regular MRI scans of the brain.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm with MRI, performed within 30 days prior to study registration.
• Patients must have received prior surgical resection and radiation therapy for the progressive meningioma.
• Patients must have received less than three prior chemotherapy regimens for progressive meningioma.
• Patients must have available an archival paraffin tumor block sufficient to generate at least 20 unstained slides; or, if a paraffin tumor block is unavailable, at least 20 unstained slides.
• Age ≥ 18 years at the time of study enrollment.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A) with no deterioration over the previous 2 weeks.
• Life expectancy of greater than three months
• Within 14 days of study registration, participants must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• hemoglobin ≥90 g/L
• platelets ≥100,000/mcL
• total bilirubin ≤1.5 x institutional upper limit of normal

You may not qualify if:

• Participants with a clinical diagnosis of NF2 (either by NIH or Manchester criteria) or with a molecular diagnosis of NF2
• Participants who received biopsy only or have received more than 2 prior courses of radiation for meningioma
• Participants who have had chemotherapy, radiotherapy, biological therapy, immunotherapy or other anticancer agents within 14 days (six weeks for nitrosoureas or mitomycin C) prior to entering the study.
• With the exception of alopecia, any unresolved toxicities from prior anti-tumor treatments (excluding corticosteroids) should be no greater than CTCAE (Version 4.0) Grade 1 at the time of study entry.
• Major surgery within four weeks prior to entry to the study (excluding placement of vascular access), or minor surgery (excluding tumor biopsies) within 14 days of first dose of study treatment.
• Participation in another clinical study with an investigational product during the last 21 days.
• History of hypersensitivity to active or inactive excipients of AZD2014 or drugs with a similar chemical structure or class to AZD2014.
• Exposure to strong or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP if taken within the stated washout periods before the first dose of study treatment (see Appendix B)
• Exposure to specific substrates of the drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K within the appropriate wash-out period (a minimum of 5 x reported elimination half-life) before the first dose of study treatment (see Appendix B)
• Any hematopoietic growth factors (e.g., filgrastim \[granulocyte colony-stimulating factor; G-CSF\], sargramostim \[granulocyte-macrophage colony-stimulating factor; GM-CSF\]) within 14 days prior to receiving study treatment.
• Pre-treatment with other mTOR inhibitors may be allowed and should be discussed with the medical monitor.
• Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
• Previous meningioma progression during treatment with other mTORC1/2 inhibitors (but not mTORC1 inhibitors such as everolimus or other rapalogs).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severe hepatic impairment, interstitial lung disease (bilateral, diffuse, parenchymal lung disease), uncontrolled chronic renal diseases (glomerulonephritis, nephrotic syndrome, Fanconi Syndrome or renal tubular acidosis), current unstable or uncompensated respiratory or cardiac conditions, uncontrolled hypertension, active bleeding diatheses, active hepatitis B or C infection, known active human immunodeficiency virus (HIV) infection, or psychiatric illness/social situations that would limit compliance with study requirements. Screening for chronic conditions is not required.
• History of other malignancies, except: Malignancy treated with curative intent and with no known active disease present for ≥5 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician, (2) adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, (3) adequately treated carcinoma in situ without evidence of disease, or (4) Gleason 6 prostate cancer under observation.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Cancer Institute (NCI): collaborator
• AstraZeneca: collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Meningioma

Interventions

vistusertib

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Scott R. Plotkin, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: March 7, 2017
• Study Start: October 17, 2017
• Primary Completion: June 30, 2022
• Study Completion: July 25, 2024
• Last Updated: October 18, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)