Status:

COMPLETED

Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas

Lead Sponsor:

Assistance Publique - Hôpitaux de Paris

Collaborating Sponsors:

Novartis

Conditions:

Neurofibromatosis Type 1

Plexiform Neurofibroma

Eligibility:

All Genders

18-60 years

Phase:

PHASE2

Brief Summary

Background: Patients with the genetic disorder neurofibromatosis Type 1 (NF1) are at increased risk of developing tumors of the central and peripheral nervous system. These include plexiform neurofib...

Detailed Description

Neurofibromatosis 1 (NF1) is an autosomal dominant disease affecting 1 in 3000 to 1 in 4000 people. NF1 is characterized by multiple dermal neurofibromas, plexiform neurofibromas, malignant peripheral...

Eligibility Criteria

Inclusion

  • Clinical diagnosis of NF1, according to NIH criteria, with internal plexiform neurofibroma (PN) and at least 1 of criteria for NF1:
  • 6 or more café-au-lait spots Freckling in the axilla or groin Optic glioma 2 or more Lisch nodules Distinctive bony lesion
  • 1-degree relative with NF1
  • At least 1 inoperable PN(s) that has/have the potential to cause significant morbidity: Paravertebral lesions that could compromise the spinal cord Head and neck lesions that could compromise the airway or great vessels Brachial or lumbar plexus lesions that could cause nerve compression and loss of function Lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems Lesions of the extremity that cause limb hypertrophy or loss of function Painful lesions
  • Complete resection of a PN with acceptable morbidity is not feasible OR patient refuses surgery OR the number of PNs leads to not feasible surgery according to the steering committee's site
  • Measurable PN amenable to volumetric MRI analysis using fusion of images
  • Measurable lesion (at least 3 cm in one dimension)
  • Karnofsky \>70%
  • 18≤ Age ≤60
  • absolute neutrophil count (ANC) ≥1.5x109/L, Platelets ≥100x109/L, Hb \>9g/dL
  • bilirubin: ≤1.5xULN, ALT and AST ≤2.5xULN unless evident Gilbert disease (amendment n°2). For patients with known liver metastases: AST and ALT ≤ 5xULN
  • Creatinine ≤ 1.5xULN
  • Life expectancy ≥ 2 years
  • Cholesterol ≤300 mg/dL or ≤7.75 mmol/L and triglycerides ≤ 2.5x ULN
  • Women of childbearing potential must have had a negative serum pregnancy test within 7 days and a negative urine pregnancy test within 72 hours prior to the administration of RAD001 start and must use an effective birth control method.
  • Men should use condoms and their partner(s) use an effective birth control method
  • A written informed consent obtained

Exclusion

  • Patients who/with:
  • have previously received mTOR inhibitors
  • a known hypersensitivity to RAD001 or other rapamycin or to its excipients
  • receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent. (Dose equivalent to 10 mg/day of methylprednisone), topical steroids or organotherapy for bilateral adrenalectomy are acceptable
  • a known history of HIV seropositivity
  • acute viral hepatitis
  • autoimmune hepatitis
  • with an active, bleeding diathesis. Patients may use coumadin or heparin preparations
  • have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation
  • have a history of another primary malignancy ≤3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Oral contraceptives are not acceptable alone
  • a contraindication to MRI
  • are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start
  • unwilling or unable to comply with the protocol
  • not affiliated to health system

Key Trial Info

Start Date :

April 1 2011

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

October 1 2014

Estimated Enrollment :

30 Patients enrolled

Trial Details

Trial ID

NCT01412892

Start Date

April 1 2011

End Date

October 1 2014

Last Update

November 14 2014

Active Locations (1)

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Page 1 of 1 (1 locations)

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Henri Mondor Hospital

Créteil, France, 94010