Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma

A Phase II, Open-label, Multi-center Study of Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma.

The purpose of this research study is to evaluate an investigational drug (Vismodegib) for Pontine Glioma that is growing or has come back (reoccurred). This study will look at the tumors response to the study drug, Vismodegib, and will also look at the safety and tolerability of Vismodegib.

Vismodegib has been tested in multiple adult clinical trials and one pediatric trial. Laboratory testing in pontine gliomas suggests that this drug may be effective in treating this disease.

Inclusion Criteria:

• Subjects must have radiographically proven diffuse intrinsic pontine glioma and confirmation of residual disease after initial therapy or at the time of recurrence/progression as confirmed by MRI of the brain
• Subjects must be age ≥3 years and ≤ 18 years
• Diffuse intrinsic pontine glioma with measurable disease after receiving radiotherapy either concurrent with or followed by ≤ 2 prior courses of chemotherapy
• Measurable disease as defined by:

Measurable tumor >10mm by MRI

• Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)

• Body surface area > 0.67 m2 and ≤ 2.21 m2

• Life expectancy of at least 2 months

• A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)

• Acceptable liver function as defined by:

  1. Bilirubin ≤ 1.5 times upper limit of normal
  2. AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age as follows:

  • 0.8 mg/dL (for patients ≤ 5 years of age)
  • 1.0 mg/dL (for patients 6 to 10 years of age)
  • 1.2 mg/dL (for patients 11 to 15 years of age)
  • 1.5 mg/dL (for patients > 15 years of age)

• Acceptable hematologic status as defined by:

  1. Granulocyte ≥ 1500 cells/mm3
  2. Platelet count ≥ 100,000 (plt/mm3)
  3. Serum albumin ≥ 2.5 g/dL

• Urinalysis:

  a. No clinically significant abnormalities

• Acceptable coagulation status as defined by:

  1. PT/INR less than 1.5
  2. PTT within normal limits

• Subjects must be able to swallow and retain oral medication

• Female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for 7 (seven) months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots).

• Male post-pubertal study subjects need to agree to use condoms with spermicide, even after a vasectomy, during sexual intercourse with female partners while being treated with Erivedge capsule and for 2 months after the last dose to avoid exposing an embryo or fetus to Vismodegib.

• Voluntarily signed and dated a written IRB-approved informed consent by parent or legal guardian of subject

Exclusion Criteria:

• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for generally about 3 weeks (8 weeks for radiotherapy) prior to the first dose of study medication, as well as recovered from toxicity (to ≤ than grade 2 except for alopecia) induced by previous treatments.

• Currently receiving another investigational medicinal product.

• Uncontrolled concurrent illness including, but not limited to:

  1. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
  2. Diarrhea of any cause ≥ CTCAE grade 2
  3. Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
  4. Any kind of malabsorption syndrome significantly affecting gastrointestinal function

• Pregnant or nursing female patients. NOTE: If a female patient becomes pregnant or suspects that she is pregnant while participating in this study, she should stop taking study drug and immediately inform her treating physician immediately.

• Prior therapy with a Hedgehog inhibitor

• Unwillingness or inability to comply with procedures required in this protocol

• Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.

• History of Congestive Heart Failure (CHF) or ventricular arrhythmia requiring medication.