Neurofibromatosis Type 2Early Phase 1NCT01880749
Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
A Early Phase 1 study testing RAD001 in people with Neurofibromatosis Type 2 and Vestibular Schwannomas, run by NYU Langone Health at 1 site in United States.
Trial summary
The primary objective is to estimate the proportions of vestibular schwannomas (VS) and meningiomas after 10 days of exposure to the study drug RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis Type 2, Vestibular Schwannomas, Meningiomas
- What is being tested?
- RAD001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Dec 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must satisfy all of the following eligibility criteria:
- Karnofsky performance status (KPS) ≥ 60%
- Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
- Platelet count ≥ 100,000/mm³ (unsupported)
- Hemoglobin ≥ 8 g/dl (transfusion support allowed)
- Creatinine ≤ 1.5 times upper limit of normal (ULN*) OR corrected glomerular filtration rate ≥ 70 ml/min
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- Total bilirubin ≤ 1.5 times ULN*
- ALT ≤ 2.5 times ULN*
- Serum albumin ≥ 2 g/dl
- INR < 1.3 (or < 3 on anticoagulants)
- Patients taking a cholesterol-lowering agent must be on a single medication and on a stable dose for at least 4 weeks
- Fasting serum cholesterol ≤ 300 mg/dl OR ≤ 7.75 mmol/l AND fasting triglycerides ≤ 2.5 times ULN*.
- Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy
- Any neurologic deficits must be stable for ≥ 1 week
- Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus.
- Able to provide written informed consent
Who cannot join
- Patients with any of the following are ineligible for this research study:
- Patients with VS or meningiomas deemed very high surgical risk for stroke and/or other complications by the attending surgeon, such as meningiomas with major vascular or dural sinus infiltration.
- Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
- Symptomatic congestive heart failure or unstable angina pectoris.
- Uncontrolled diabetes, as defined by fasting serum glucose >1.5 times ULN*.
- Current active hepatic or biliary disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis (with exception of patients with Gilbert's syndrome and asymptomatic gallstones).
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- History of hepatitis B or C. Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV serology, DNA and/or HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection. If no positive medical history for risk factors, serology is not required.
- Seropositivity or DNA/RNA positivity for hepatitis B or C, with the exception of patients who have received prior Hepatitis B vaccination and are Anti-HBs positive only.
- Known HIV seropositivity
- Neurologic deficits that are rapidly progressing: all neurologic signs and symptoms must have been stable for a week prior to first dose
- Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant.
- Anti-tumor therapy (i.e. chemotherapeutics or investigational agents or immunotherapy) within 4 weeks prior to enrollment
- Radiation therapy to a study target lesion within 6 months
- Prior therapy with mTOR inhibitors, including sirolimus, temsirolimus, deforolimus within 6 months prior to enrollment
- Known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus, deforolimus)
- Patients with a concurrent malignancy
- Patients treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.
- Patients cannot receive CYP3A4 inhibiting drugs including antibiotics (clarithromycin, erythromycin, troleandomycin), anti-HIV agents (delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir), antifungals (itraconazole, ketoconazole, fluconazole at doses > 200 mg/day, voriconazole), antidepressants (nefazodone, fluovoxamine), calcium channel blockers (verapamil, diltiazem) oramiodarone
- Patients should avoid CYP3A4 inhibiting foods including grapefruit and Seville orange juice.
- Patients cannot receive CYP3A4 inducing anticonvulsants including carbamazepine, felbamate, phenobarbital, phenytoin, primidone and oxcarbazepine, or other CYP3A4 inducers such as St. John's Wort
- Patients who previously received CYP3A4 inducers or inhibitors must have discontinued these medications within at least 1 week prior to study entry and can re-start them 1 week post-operatively (or earlier if determined to be of clinical benefit, as determined by the treating physician).
- of institutional norms
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University School of Medicine
New York, New York, 10016
About this study
The primary objective is to estimate the proportions of vestibular schwannomas (VS) and meningiomas after 10 days of exposure to the study drug RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This is a "phase 0" PK (pharmacokinetic) and PD (pharmacodynamic) study of RAD001 in patients with Neurofibromatosis Type 2-related and sporadic VS and meningiomas. Enrolled patients will take RAD001 prior to a scheduled VS or meningioma surgery, and blood and tissue samples will be obtained for further analysis.
- Being tested
- RAD001
- Medical subject headings
- Neurofibromatosis 2, Neuroma, Acoustic, Meningioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called Everolimus
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Experimental | RAD001 taken by mouth 10mg daily for 10 days before surgery Receives: Drug: RAD001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportions of VS and meningiomas after exposure to RAD001
- To estimate the proportions of VS and meningiomas with complete inhibition of phospho-S6 after10 days of exposure to RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This endpoint was chosen based on prior pharmacodynamic data from a published trial, showing complete inhibition of phospho-S6 in solid tumor tissue of patients treated with RAD001 and our own preliminary data confirming baseline phospho-S6 expression in VS and meningiomas.
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis Type 2Studies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Theodore Nicolaides, MD, Study chair, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01880749
- Sponsor's protocol ID
- 12-02808
- Status last verified
- May 2020
- First submitted
- 11 Jun 2013
- Last updated
- 13 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
- ClinicalTrials.gov ID
- NCT01880749
- Acronym / sponsor ID
- 12-02808
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 19 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to estimate the proportions of vestibular schwannomas (VS) and meningiomas after 10 days of exposure to the study drug RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This is a "phase 0" PK (pharmacokinetic) and PD (pharmacodynamic) study of RAD001 in patients with Neurofibromatosis Type 2-related and sporadic VS and meningiomas. Enrolled patients will take RAD001 prior to a scheduled VS or meningioma surgery, and blood and tissue samples will be obtained for further analysis.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Experimental | Drug: RAD001RAD001 taken by mouth 10mg daily for 10 days before surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must satisfy all of the following eligibility criteria:
- Karnofsky performance status (KPS) ≥ 60%
- Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
- Platelet count ≥ 100,000/mm³ (unsupported)
- Hemoglobin ≥ 8 g/dl (transfusion support allowed)
Key exclusion criteria (22 listed)
- Patients with any of the following are ineligible for this research study:
- Patients with VS or meningiomas deemed very high surgical risk for stroke and/or other complications by the attending surgeon, such as meningiomas with major vascular or dural sinus infiltration.
- Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
- Symptomatic congestive heart failure or unstable angina pectoris.
- Uncontrolled diabetes, as defined by fasting serum glucose >1.5 times ULN*.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001Also: Everolimus | Drug | RAD001 |
Primary outcome
Proportions of VS and meningiomas after exposure to RAD001
Time frame: 10 days
1) To estimate the proportions of VS and meningiomas with complete inhibition of phospho-S6 after10 days of exposure to RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This endpoint was chosen based on prior pharmacodynamic data from a published trial, showing complete inhibition of phospho-S6 in solid tumor tissue of patients treated with RAD001 and our own preliminary data confirming baseline phospho-S6 expression in VS and meningiomas.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theodore Nicolaides, MD study chair
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing RAD001 in people with Neurofibromatosis Type 2 and Vestibular Schwannomas, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportions of VS and meningiomas after exposure to RAD001 (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2020.