AzTrials
AzTrials

Recurrent Childhood MedulloblastomaPhase 1NCT00822458

GDC-0449 in Treating Young Patients With Medulloblastoma That is Recurrent or Did Not Respond to Previous Treatment

A Phase 1 study testing vismodegib, laboratory biomarker analysis and pharmacological study in people with Recurrent Childhood Medulloblastoma, run by National Cancer Institute (NCI) at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 3 to 21 years
Conditions the study is for
Recurrent Childhood Medulloblastoma
What is being tested?
vismodegib, laboratory biomarker analysis and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
9 sitesUnited States
Study dates
Jan 2009to Sep 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)
Show all 38Show fewer
  • 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
  • ALT/AST ≤ 2.5 times ULN for age
  • Serum albumin ≥ 2.5 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile female patients must use 2 effective methods of contraception during and for 12 months following study treatment
  • Fertile male patients must use effective barrier contraception during and for 12 months following study treatment
  • Body surface area > 0.67 m^2 and ≤ 2.5 m^2
  • Able to swallow capsules
  • No malabsorption syndrome or other condition that would interfere with enteral absorption
  • No history of congestive heart failure
  • No history of ventricular arrhythmia requiring medication
  • No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation
  • No clinically important history of liver disease, including viral hepatitis or cirrhosis
  • No concurrent clinically significant unrelated systemic illness (e.g., serious infection) or significant cardiac, pulmonary, hepatic, or other organ dysfunction that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results
  • NOTE: * In the absence of bone marrow involvement
  • Recovered from prior treatment-related toxicity
  • At least 3 months since prior craniospinal radiotherapy (at doses ≥ 23 Gy)
  • At least 8 weeks since prior local radiotherapy to primary tumor
  • At least 2 weeks since prior focal radiotherapy to symptomatic metastatic sites
  • More than 4 weeks since prior myelosuppressive chemotherapy or immunotherapy (6 weeks for nitrosoureas)
  • More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)
  • No other concurrent anticancer or investigational drug therapy
  • Concurrent dexamethasone allowed provided dosage is stable or decreasing for ≥ 1 week prior to study entry

Who cannot join

None listed.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60614

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Pediatric Brain Tumor Consortium

    Memphis, Tennessee, 38105

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • UCSF-Mount Zion

    San Francisco, California, 94115

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase I Pharmacokinetic and Safety Study in Children With Recurrent or Refractory Medulloblastoma to Identify a Pharmacokinetic Based Dose for GDC-0449

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To investigate the safety and pharmacokinetics of a daily dose of hedgehog antagonist GDC-0449 using the available formulation in pediatric patients with recurrent or refractory medulloblastoma.

SECONDARY OBJECTIVES:

  1. To document and describe toxicities associated with this drug in these patients.

II. To characterize the pharmacokinetics of this drug in these patients. III. To document preliminary antitumor activity of this drug in these patients. IV. To document pathologic and genomic methods to identify CNS tumors with activation of the PTCH/SHH pathway.

OUTLINE: This is a multicenter study.

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.

After completion of study therapy, patients are followed for 90 days.

Being tested
vismodegib, laboratory biomarker analysis, pharmacological study
Medical subject headings
Medulloblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vismodegibDrug

    Also called Erivedge, GDC-0449, Hedgehog antagonist GDC-0449

    Given orally

  • laboratory biomarker analysisOther

  • pharmacological studyOther

    Also called pharmacological studies

Study groups in NCT00822458
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: vismodegib; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    95% confidence interval estimates for 2 doses compared.

    Measured: 21 days

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

    We will study two BSA defined strata.

    Measured: Up to 3 months after completion of study treatment

Secondary outcomes (2)

  1. Tumor responses

    Descriptive statistics will be provided describing tumor responses.

    Measured: Up to 30 days after completion of study treatment

  2. Progression-free survival

    Kaplan-Meier estimates of the distribution of progression-free survival (PFS) will be constructed.

    Measured: Up to 30 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2009 (estimated)
  2. Study startJan 2009
  3. Primary completionSep 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00822458
Sponsor's protocol ID
NCI-2009-01180
Other IDs
NCI-2009-01180, CDR0000631677, PBTC-025, PBTC-025, U01CA081457
Status last verified
Jun 2013
First submitted
13 Jan 2009
Last updated
2 Apr 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vismodegib, laboratory biomarker analysis and pharmacological study in people with Recurrent Childhood Medulloblastoma, run by National Cancer Institute (NCI) at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean steady-state total (protein bound and non-protein bound) GDC-0449 plasma concentrations (Css) (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00822458.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in