Vismodegib in Treating Patients With Recurrent or Refractory Medulloblastoma

NCT00939484 | Completed Phase 2 Results

• 3 other identifiers: NCI-2012-03020PBTC-025BU01CA081457
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Adult Medulloblastoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 months

Secondary Outcomes (3)

• Progression-free Survival

  From start of treatment up to 2 years

• Duration of Objective Response

  From start of treatment up to 2 years

• Pharmacokinetic Parameters of Vismodegib, CSF Penetration

  up to 12 month

Study Arms (1)

Treatment (vismodegib)

EXPERIMENTAL

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.

Other: Pharmacological Study; Drug: Vismodegib

Interventions

Pharmacological Study OTHER

Correlative studies

Treatment (vismodegib)

Vismodegib DRUG

Given PO

Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

Treatment (vismodegib)

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-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, 60611, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, 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

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I, Packer RJ, Goldman S, Prados MD, Desjardins A, Chintagumpala M, Takebe N, Kaste SC, Rusch M, Allen SJ, Onar-Thomas A, Stewart CF, Fouladi M, Boyett JM, Gilbertson RJ, Curran T, Ellison DW, Gajjar A. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032. J Clin Oncol. 2015 Aug 20;33(24):2646-54. doi: 10.1200/JCO.2014.60.1591. Epub 2015 Jul 13.

  PMID: 26169613 DERIVED

MeSH Terms

Conditions

Medulloblastoma

Interventions

HhAntag691

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Tong Lin (Biostatistician)
• Organization: St. Jude Children's Research Hospital

Tong.Lin@stjude.org

9015952048

Study Officials

• Amar Gajjar

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: July 15, 2009
• Study Start: June 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: August 1, 2015
• Last Updated: February 25, 2016
• Results First Posted: February 25, 2016

Record last verified: 2015-03

Locations

US (13)