Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00939484
First received: July 14, 2009
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Adult Medulloblastoma
Drug: vismodegib
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial Evaluating the Efficacy and Safety of GDC-0449 in Adults With Recurrent or Refractory Medulloblastoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rates (PR and CR) graded using RECIST criteria [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Ninety-five percent confidence interval estimates of the true, unknown objective response rate will be constructed for each of the three strata. The proportions of patients with confirmed complete responses, partial responses and stable disease will be reported descriptively for each of the three strata. Cumulative incidence functions of time to objective response will also be provided.


Secondary Outcome Measures:
  • Duration of sustained objective response [ Time Frame: From the initial scan documenting complete or partial response that was subsequently confirmed until the earlier of documented progression or death on study, assessed up to 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be constructed.

  • Progression-free survival [ Time Frame: From the date of initial treatment with GDC-0449 until the earliest of progression or death on study, assessed up to 12 months ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be constructed.


Other Outcome Measures:
  • Pharmacokinetic parameters of vismodegib, estimated using compartmental methods [ Time Frame: Up 12 months ] [ Designated as safety issue: No ]
    Plasma and cerebrospinal fluid (CSF) drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form.


Estimated Enrollment: 50
Study Start Date: June 2009
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vismodegib)
Patients receive vismodegib 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.
Drug: vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Hedgehog antagonist GDC-0449
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   22 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a histologically confirmed diagnosis of medulloblastoma (including posterior fossa PNET) that is recurrent, progressive, or refractory to standard therapy and for which there is no known curative therapy are eligible; there must be evidence of residual measurable disease or lesion in pre-study MRI as described in section; patients with spinal disease that is measurable will be eligible
  • The diagnosis should be confirmed at the treating institution and tissue (either from the diagnosis or relapse or preferably from both time points) must be available for biological studies
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0- 2
  • No other myelosuppressive chemotherapy or immunotherapy within 4 weeks prior to study entry (6 weeks if prior nitrosourea)
  • 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 (>= 23 Gy); >= 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 (GCSF, GM CSF, erythropoietin)
  • Absolute neutrophil count (ANC) >= 1000/μL
  • Platelet count >= 50,000/uL (transfusion independent)
  • Hemoglobin >= 8.0 gm/dL (may receive RBC transfusions)
  • Creatinine clearance or radio-isotope GFR >= 70ml/min/1.73 m2 or
  • A serum creatinine =< 2.0 mg/dL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x institutional ULN
  • Serum glutamic-oxalacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 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
  • 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 use 2 forms of acceptable contraception, including one barrier method during participation in the study and for the 12 months following the last dose; for medical or personal reasons, 100% commitment to abstinence is considered an acceptable form of birth control. All patients should receive contraceptive counseling either by the investigator, or by an OB/gynecologist or other physician who is qualified in this area of expertise; 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
  • Signed informed consent according to institutional guidelines must be obtained

Exclusion Criteria:

  • 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
  • Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
  • Life expectancy < 12 weeks as determined by treating physician
  • Inability to swallow capsules
  • Prior treatment with GDC-0449 or other antagonists of the HH pathway
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • 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
  • Congenital long QT syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00939484

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
UCSF-Mount Zion
San Francisco, California, United States, 94115
University of California at San Francisco - Comprehensive Cancer Center
San Francisco, California, United States, 94143-0875
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60611
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Pediatric Brain Tumor Consortium
Memphis, Tennessee, United States, 38105
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Amar Gajjar Pediatric Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00939484     History of Changes
Other Study ID Numbers: NCI-2012-03020, NCI-2012-03020, PBTC-025B, PBTC-025B, U01CA081457
Study First Received: July 14, 2009
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Medulloblastoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive

ClinicalTrials.gov processed this record on October 20, 2014