AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas

• Register: ClinicalTrials.gov
• Last refreshed on: 20 June 2022
• Main ID: NCT02831257
• Date of registration: 07/07/2016
• Prospective Registration: Yes
• Primary sponsor: Massachusetts General Hospital
• Public title: AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas
• Scientific title: A Single Arm Phase 2 Study of the Dual mTORC1/mTORC2 Inhibitor AZD2014 Provided on an Intermittent Schedule for Neurofibromatosis 2 Patients With Progressive or Symptomatic Meningiomas
• Date of first enrolment: August 31, 2016
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02831257
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Scott Plotkin, MD, PhD
• Affiliation: Massachusetts General Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- hemoglobin =90 g/L

- platelets =100,000/mcL

- total bilirubin =1.5 x institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) =2.5 × institutional upper limit of normal

- Serum creatinine =1.5 x institutional upper limit of normal concurrent with
creatinine clearance =50 mL/min (measured or calculated by Cockcroft and Gault
equation), confirmation of creatinine clearance is only required when creatinine
is >1.5xULN

- Urine protein =1+ on urine dipstick (if 2+ seen on first test, re-test at least
24 hours later)

- PT/INR/PTT (aPTT) <1.5x institutional upper limit of normal

- The effects of AZD2014 on the developing human fetus are unknown. For this reason and
because mTOR kinase inhibiting agents are known to be teratogenic, female patients
must be willing to use 2 forms of highly effective contraception (per institution
standards) from the time of screening until 4 weeks after discontinuing study, must
not be breast feeding and must have a negative pregnancy test prior to start of dosing
if of child bearing potential or must have evidence of non-childbearing potential by
fulfilling one of the following criteria at screening: (1) post-menopausal women,
defined as either women aged more than 50 years and amenorrhoeic for at least 12
months following cessation of all exogenous hormonal treatments, or, (2) women under
50 years old who have been amenorrhoeic for at least 12 months following the cessation
of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH)
and luteinizing hormone (LH) levels in the postmenopausal range for the institution.
Alternatively, women must have documentation of irreversible surgical sterilisation by
hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal
ligation.

- Male patients should either be surgically sterile or willing to use an effective
barrier method of contraception during the study and for 16 weeks following the last
dose of study treatment if sexually active with a female of childbearing potential. If
not done previously, storage of sperm prior to receiving AZD2014 will be advised to
male patients with a desire to have children.

- Ability to understand and the willingness to sign a written informed consent document
prior to any study specific procedures, sampling, and analyses.

- Ability to swallow and retain oral medication

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neurofibromatosis 2

Meningioma

Intervention(s)

Drug: AZD2014

Primary Outcome(s)

Radiographic Response Rate for Target Meningioma [Time Frame: up to 24 months]

Secondary Outcome(s)

Median Progression-free Survival (PFS) [Time Frame: From date of registration until the date of first documented progression assessed up to 24 months]

Vestibular Schwannoma-Specific Quality of Life [Time Frame: Baseline, after 3 months of treatment, and off study (up to 24 months)]

Radiographic Response Rate of Vestibular Schwannomas [Time Frame: up to 24 months]

Number of Participants With Grade 2 Adverse Events [Time Frame: up to 24 months]

Number of Participants With Grade 3 Adverse Events [Time Frame: up to 24 months]

Radiographic Response Rate for Non-target Meningiomas [Time Frame: up to 24 months]

Disease-Specific Quality of Life [Time Frame: Baseline, after 3 months of treatment, and off study (up to 24 months)]

Progression Free Survival at 6 Month [Time Frame: 6 months of treatment]

Secondary ID(s)

15-590

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

United States Department of Defense

AstraZeneca

Results

• Results available: Yes
• Date Posted: 22/12/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02831257