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

This is an interventional treatment trial for Pontine Glioma focused on measuring DIPG Read More

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.