NCT00822458

Brief Summary

This phase I trial is studying the side effects and best dose of GDC-0449 in treating young patients with medulloblastoma that is recurrent or did not respond to previous treatment. GDC-0449 may be effective in treating young patients with medulloblastoma.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2009

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

January 13, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 14, 2009

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2013

Completed
Last Updated

April 2, 2014

Status Verified

June 1, 2013

Enrollment Period

4.7 years

First QC Date

January 13, 2009

Last Update Submit

April 1, 2014

Conditions

Recurrent Childhood Medulloblastoma

Outcome Measures

Primary Outcomes (2)

  • Mean steady-state total (protein bound and non-protein bound) GDC-0449 plasma concentrations (Css)

    95% confidence interval estimates for 2 doses compared.

    21 days

  • Pharmacokinetics of GDC-0449, including the elimination rate constant and terminal half life

    We will study two BSA defined strata.

    Up to 3 months after completion of study treatment

Secondary Outcomes (2)

  • Tumor responses

    Up to 30 days after completion of study treatment

  • Progression-free survival

    Up to 30 days after completion of study treatment

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral hedgehog antagonist GDC-0449 once daily on days 1 and 4-28 in course 1 and on days 1-28 in all subsequent courses. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic studies. Archival tumor tissue samples are collected and analyzed for the expression of genes that activate the SHH (e.g., Gli1, Gli2, SFRP1, ATOH1, and PTCH2) or WNT (e.g., DKK2 and DKK4) cell signal pathways by in situ hybridization and reverse transcriptase real time-PCR.

Drug: vismodegibOther: laboratory biomarker analysisOther: pharmacological study

Interventions

vismodegibDRUG

Given orally

Also known as: Erivedge, GDC-0449, Hedgehog antagonist GDC-0449
Arm I
laboratory biomarker analysisOTHER
Arm I
pharmacological studyOTHER
Also known as: pharmacological studies
Arm I

Eligibility Criteria

Age3 Years - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Histologically confirmed medulloblastoma, including posterior fossa primitive neuroectodermal tumor (PNET)
  • Recurrent, progressive, or refractory to standard therapy
  • No known curative therapy exists
  • Neurological deficits allowed provided they are stable for ≥ 1 week prior to study entry
  • No atypical teratoid/rhabdoid tumor or supratentorial PNET
  • Karnofsky performance status (PS) 60-100% (for patients \> 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)
  • ANC ≥ 1,000/μL\*
  • Platelet count ≥ 100,000/μL (transfusion independent)\*
  • Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed)\*
  • 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)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • +23 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

UCSF-Mount Zion

San Francisco, California, 94115, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60614, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Medulloblastoma

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

GliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeuroectodermal Tumors, PrimitiveNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • Amar Gajjar

    Pediatric Brain Tumor Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2009

First Posted

January 14, 2009

Study Start

January 1, 2009

Primary Completion

September 1, 2013

Last Updated

April 2, 2014

Record last verified: 2013-06

Locations

US(9)