Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma
Condition: Pontine Glioma
MeSH terms: Glioma
Intervention: Vismodegib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 3 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: DIPG

Summary:

      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.
    

Eligibility criteria:

        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.