This phase II trial is studying how well vismodegib works in treating adult patients with recurrent or refractory medulloblastoma. Vismodegib may slow the growth of tumor cells and may be an effective treatment for medulloblastoma.
PRIMARY OBJECTIVES: I. To estimate the efficacy of GDC-0449 (vismodegib) treatment for adult patients with recurrent or refractory medulloblastoma, as measured by the objective response rates for patients without (Stratum A) and with (Stratum B) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of GDC-0449 administered on a once daily schedule. II. To estimate the duration of objective response and progression-free survival (PFS). III. To characterize the pharmacokinetics (plasma and cerebrospinal fluid) of GDC-0449 in adults with refractory medulloblastoma. IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway. V. To describe the objective responses observed in patients whose pathologic assessment of tumor result in unknown (Stratum C) evidence of activation of Sonic Hedgehog (SHH) signaling pathway tumors. OUTLINE: This is a multicenter study. Patients are stratified according to PTCH/Sonic Hedgehog signaling pathway activation (inactivated vs activated vs unknown). Patients receive vismodegib orally (PO) once daily on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for up to 12 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Correlative studies
Given PO
Children's Hospital Los Angeles
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
UCSF Medical Center-Mount Zion
Objective Response (CR+PR) Sustained for ≥ 8 Weeks
Objective response is either a complete response or a partial response sustained for 8 weeks in a patient. The objective response rate will be reported separately for patients of each stratum. CR is complete disappearance of all enhancing tumor. PR is \>= 50% reduction in tumor size.
Time frame: Up to 12 months
Progression-free Survival
Progression-free survival (PFS) is measured from the date of initial treatment with GDC-0449 until the earliest of progression or death on study. PFS is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment. Kaplan-Meier method is used to estimate the progression-free survival.
Time frame: From start of treatment up to 2 years
Duration of Objective Response
The duration of objective response is measured from the initial scan documenting complete or partial response that was subsequently confirmed until the earlier of documented progression or death on study. Duration of objective response is censored at the last tumor assessment date for patients without disease progression who have not died within 30 days of last exposure to study treatment.
Time frame: From start of treatment up to 2 years
Pharmacokinetic Parameters of Vismodegib, CSF Penetration
The estimated median of cerebrospinal fluid (CSF) drug penetration is reported when expressed as an AUC ratio of CSF vismodegib to that of unbound drug in plasma.
Time frame: up to 12 month
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
...and 3 more locations