| Eligibility |
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.
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