AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas

NCT02831257 | Completed Phase 2 Results DMC

• 1 other identifier: 15-590
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to learn if the study drug AZD2014 can shrink growing or symptomatic meningiomas.

Conditions

Neurofibromatosis 2; Meningioma

Keywords

Neurofibromatosis 2

Outcome Measures

Primary Outcomes (1)

• Radiographic Response Rate for Target Meningioma

  Number of Target Meningiomas with a Decrease in Tumor Volume of at least 20% Compared with Baseline

  up to 24 months

Secondary Outcomes (8)

• Median Progression-free Survival (PFS)

  From date of registration until the date of first documented progression assessed up to 24 months

• Progression Free Survival at 6 Month

  6 months of treatment

• Radiographic Response Rate for Non-target Meningiomas

  up to 24 months

• Number of Participants With Grade 3 Adverse Events

  up to 24 months

• Radiographic Response Rate of Vestibular Schwannomas

  up to 24 months

Study Arms (1)

AZD2014

EXPERIMENTAL

18 patients will be enrolled in this study in a single stage. * AZD2014 orally, 2 times a day on 2 consecutive day out of every 7 days. * One cycle will consist of 28 days (1 cycle = 28 days).

Drug: AZD2014

Interventions

AZD2014 DRUG

AZD2014

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the NF2 gene.
• Participants must have progressive or symptomatic meningioma. NOTE 1: Histologic confirmation of meningioma is not required in the setting of compatible radiographic appearance, NOTE2: progression is defined as an increase in target meningioma volume ≥ 20% OR ≥ 3 mm during the past 2 years.
• \-- Subjects must have a target meningioma that is not amenable to surgery due to patient preference or high risk for surgical complications
• Participants must be willing and able to undergo regular MRI scans of the brain
• Patients must have measurable disease, defined as at least one meningioma ≥ 1.0 ml that can be accurately measured by contrast-enhanced cranial MRI scan, performed within 28 days of study registration.
• Prior surgical resection and radiation therapy for the progressive meningioma are not required for study enrollment.
• Patients must have received less than 3 prior chemotherapy regimens for progressive meningioma.
• Patients receiving dexamethasone must be able to be treated with alternative corticosteroids such as prednisone, prednisolone, or methylprednisolone in the opinion of the treating physician.
• 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%) with no deterioration over the previous 2 weeks
• Life expectancy of greater than 3 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

You may not qualify if:

• Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents within 21 days of starting study treatment (not including palliative radiotherapy at focal sites). Prior use of an investigational monoclonal antibody therapy within 3 months, or prior use of nitrosoureas or mitomycin C within 6 weeks. Patients must have recovered from acute toxicity due to radiotherapy.
• 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 4 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 potent 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 sensitive or narrow therapeutic range substrates of the drug metabolizing enzymes CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 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 haemopoietic 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 for each protocol and tumor type separately
• 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 rapalogues)
• 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.
• Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months:
• coronary artery bypass graft

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• AstraZeneca: collaborator
• United States Department of Defense: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 2; Meningioma

Interventions

vistusertib

Condition Hierarchy (Ancestors)

Neuroma, Acoustic; Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Scott Plotkin
• Organization: Massachusetts General Hospital

splotkin@mgh.harvard.edu

617-724-5369

Study Officials

• Scott Plotkin, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: July 7, 2016
• First Posted: July 13, 2016
• Study Start: August 31, 2016
• Primary Completion: May 31, 2019
• Study Completion: October 1, 2020
• Last Updated: June 13, 2022
• Results First Posted: December 22, 2020

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)