Vismodegib in Treating Younger Patients With Recurrent or Refractory Medulloblastoma

Not Recruiting

Trial ID: NCT01239316


This phase II trial studies how well vismodegib works in treating younger patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells.

Official Title

A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Children With Recurrent or Refractory Medulloblastoma

Stanford Investigator(s)

Paul Graham Fisher, MD
Paul Graham Fisher, MD

Beirne Family Professor of Pediatric Neuro-Oncology, Professor of Pediatrics and, by courtesy, of Neurosurgery and of Epidemiology and Population Health


Inclusion Criteria:

   - Patients with a histologically confirmed diagnosis of medulloblastoma that is
   recurrent, progressive, or refractory to standard therapy and for which there is no
   known curative therapy

   - Patient must have adequate archival formalin fixed, paraffin embedded (FFPE) primary
   tumor material for biology studies; specifically, adequate archival FFPE tumor
   material is either:

      - An FFPE block, preferably in which tumor occupies an area of at least 10x10 mm if
      available, and is free of surgical or processing artifacts; tumor in the
      submitted FFPE block must not have been obtained from the CUSA trap OR

      - Preferably15x5µm sections if available from an FFPE tissue block conforming to
      the above criteria AND

      - Tissue submission must be accompanied by a copy of the pathology report

   - Patients must have bi-dimensionally measureable disease in the brain or spinal cord
   defined as at least one lesion that can be accurately measured in at least 2 planes in
   order to be eligible for this study

   - Patients must have a body surface area (BSA) of >= 0.67m^2 and at most 2.5m^2

   - Patients with neurological deficits should have deficits that are stable for a minimum
   of 1 week prior to registration; this is to be documented in the database

   - Karnofsky performance status of >= 50% in patients > 16 years, or Lansky performance
   status of >= 50% in patients >= 3 yrs and =< 16 years, assessed within two weeks prior
   to registration

   - Must have recovered from prior treatment-related toxicity; no other myelosuppressive
   chemotherapy or immunotherapy within 4 weeks prior to study entry (6 weeks if prior

   - Decadron dose should also be stable or decreasing for at least 1 week (7days) prior to
   starting therapy

   - Radiation therapy (XRT) >= 3 months prior to study entry for craniospinal irradiation;
   >= 8 weeks for local irradiation to primary tumor; >= 2 weeks prior to study entry for
   focal irradiation for symptomatic metastatic sites

   - Off all colony stimulating factors > 1 week prior to study entry (granulocyte colony
   stimulating factor [GCSF], granulocyte macrophage colony stimulating factor [GM CSF],

   - Prior therapy will include primary therapy (including radiation therapy and
   chemotherapy) and a maximum of 2 additional salvage therapies; patients can enroll on
   the protocol after failure on primary therapy

   - Absolute neutrophil count (ANC) >= 1000 µL

   - Platelet count >= 50,000/uL (transfusion independent)

   - Hemoglobin >= 8.0 gm/dL (may receive red blood cell [RBC] transfusions)

   - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73
   m^2 or a serum creatinine =< 1.5 mg/dL

   - Serum Total Bilirubin =< 1.5 x upper limit of normal (ULN) for age

   - Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5
   times institutional ULN for age

   - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
   2.5 times institutional ULN for age

   - Alkaline Phosphatase =< 1.5 times institutional ULN

   - Serum albumin >= 2.5 g/dL

   - Patient must have recovered from the significant acute toxicities of all prior therapy
   before entering this study and meet all other eligibility criteria specified in the
   Inclusion and Exclusion Criteria

   - Pregnancy should be avoided for 12 months after the last dose of GDC-0449 for females
   of child-bearing potential; female patients of childbearing potential must not be
   pregnant or breast-feeding; female patients of childbearing potential must have a
   negative serum or urine pregnancy test within 24 hours prior to beginning treatment

   - Women of childbearing potential are required to have a negative serum pregnancy test
   (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior
   to the first dose of GDC-0449 (serum or urine); a pregnancy test (serum or urine) will
   be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks
   if their cycles are irregular while on study within the 24-hour period prior to the
   administration of GDC-0449; prior to dispensing GDC-0449, the investigator must
   confirm and document the patient's use of two contraceptive methods, dates of negative
   pregnancy test, and confirm the patient's understanding of the of GDC-0449 to cause
   spontaneous abortion or birth defects; female patients are required to use two forms
   of acceptable contraception, including one barrier method during participation in the
   study and for the 12 months following the last dose; all patients should receive
   contraceptive counseling either by the investigator, or by an obstetrician (OB),
   gynecologist or other physician who is qualified in this area of expertise; if a woman
   of childbearing potential believes that her contraceptive method has failed, emergency
   contraception should be considered; if a patient is suspected to be pregnant, GDC-0449
   should be immediately discontinued; in addition, a positive urine test must be
   confirmed by a serum pregnancy test; if it is confirmed that the patients is not
   pregnant, the patient may resume dosing with GDC-0449; if a female patient becomes
   pregnant during therapy or within 12 months after the last dose of GDC-0449, or if the
   female partner of a male patient exposed to the drug becomes pregnant while the male
   patient is receiving GDC-0449 or within 12 months after the last dose of GDC-0449, the
   investigator must be notified in order to facilitate outcome follow-up; female
   patients should not breastfeed a baby while on this study; female patients must NEVER
   donate ova while being treated with GDC-0449; all sexually active male subjects
   (including those who have undergone vasectomy) should utilize a barrier form of
   contraception during study treatment and for 12 months after the last dose as it is
   not known whether GDC-0449 that may be present in seminal fluid would cause serious or
   life-threatening birth defects in a fetus born to the female partner of a male
   subject; males should also not donate sperm during treatment or up to 12 months after
   the last dose

   - Signed informed consent must be obtained including for pharmacokinetic study according
   to institutional guidelines

Exclusion Criteria:

   - Central nervous system (CNS) embryonal tumor other than medulloblastoma; for example,
   patients with diagnosis of Atypical Teratoid / Rhabdoid Tumor (ATRT), primitive
   neuroectodermal tumor (PNET) from a non-cerebellar site within the central nervous
   system, ependymoblastoma, or medulloepithelioma

   - Patients with any clinically significant unrelated systemic illness (serious
   infections or significant cardiac, pulmonary, hepatic or other organ dysfunction),
   that would compromise the patient's ability to tolerate protocol therapy or would
   likely interfere with the study procedures or results

   - Patients receiving any other anticancer or investigational drug therapy, or warfarin

   - Patients with inability to return for follow-up visits or obtain follow-up studies
   required to assess toxicity to therapy

   - Other: below given criteria are confirmed by the patient history

      - Inability to swallow capsules

      - Malabsorption syndrome or other condition that would interfere with enteral

      - History of congestive heart failure

      - History of ventricular arrhythmia requiring medication

      - Uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as
      less than the lower limit of normal for the institution despite adequate
      electrolyte supplementation

      - Clinically important history of liver disease, including viral or other hepatitis
      or cirrhosis


drug: vismodegib

other: pharmacological study

other: laboratory biomarker analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Prianka Kumar

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