Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Spectrum Health Hospitals
Sponsor:
Collaborators:
Spectrum Health Hospitals
Phoenix Children's Hospital
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT01774253
First received: January 18, 2013
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

The purpose of this research study is to evaluate an investigational drug (Vismodegib) for Pontine Glioma that is growing or has come back (reoccurred). This study will look at the tumors response to the study drug, Vismodegib, and will also look at the safety and tolerability of Vismodegib.

Vismodegib has been tested in multiple adult clinical trials and one pediatric trial. Laboratory testing in pontine gliomas suggests that this drug may be effective in treating this disease.


Condition Intervention Phase
Pontine Glioma
Drug: Vismodegib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Open-label, Multi-center Study of Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma.

Resource links provided by NLM:


Further study details as provided by Spectrum Health Hospitals:

Primary Outcome Measures:
  • Determine the Progression Free Survival (PFS) of Participants using days until progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To determine the activity of Vismodegib based on Progression Free Survival (PFS) in pediatric and adolescent subjects with refractory or recurrent pontine glioma.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the safety and tolerability of Vismodegib as a single agent in pediatric and young adult patients with refractory or recurrent pontine glioma

  • Determine the Median overall survival (OS) of Participants [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)

  • Evaluate the impact of Quality of Life of children receiving Vismodegib using PedsQL questionnaires [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the impact of QOL of children receiving Vismodegib

  • Determine the response rates of Participants based on activation (or no activation) of their hedgehog signaling pathway [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the objective response rates (partial and complete response) for patients without and with evidence of activation of Hedgehog signaling pathway in their tumors


Estimated Enrollment: 48
Study Start Date: May 2013
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vismodegib
Vismodegib will be dosed at 150mg-300mg orally (max dose: 300mg) once a day on days 1 to 28 of a 28-day cycle. In the absence of unacceptable toxicity or disease progression, treatment may continue for as long as tolerated.
Drug: Vismodegib
Other Name: Erivedge

  Eligibility

Ages Eligible for Study:   3 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have radiographically proven diffuse intrinsic pontine glioma and confirmation of residual disease after initial therapy or at the time of recurrence/progression as confirmed by MRI of the brain
  • Subjects must be age ≥3 years and ≤ 18 years
  • Diffuse intrinsic pontine glioma with measurable disease after receiving radiotherapy either concurrent with or followed by ≤ 2 prior courses of chemotherapy
  • Measurable disease as defined by:

Measurable tumor >10mm by MRI

  • Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)
  • Body surface area > 0.67 m2 and ≤ 2.21 m2
  • Life expectancy of at least 2 months
  • A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
  • Acceptable liver function as defined by:

    1. Bilirubin ≤ 1.5 times upper limit of normal
    2. AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal
  • 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)
  • Acceptable hematologic status as defined by:

    1. Granulocyte ≥ 1500 cells/mm3
    2. Platelet count ≥ 100,000 (plt/mm3)
    3. Serum albumin ≥ 2.5 g/dL
  • Urinalysis:

    a. No clinically significant abnormalities

  • Acceptable coagulation status as defined by:

    1. PT/INR less than 1.5
    2. PTT within normal limits
  • Subjects must be able to swallow and retain oral medication
  • Female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for 7 (seven) months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots).
  • Male post-pubertal study subjects need to agree to use condoms with spermicide, even after a vasectomy, during sexual intercourse with female partners while being treated with Erivedge capsule and for 2 months after the last dose to avoid exposing an embryo or fetus to Vismodegib.
  • Voluntarily signed and dated a written IRB-approved informed consent by parent or legal guardian of subject

Exclusion Criteria:

  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for generally about 3 weeks (8 weeks for radiotherapy) prior to the first dose of study medication, as well as recovered from toxicity (to ≤ than grade 2 except for alopecia) induced by previous treatments.
  • Currently receiving another investigational medicinal product.
  • Uncontrolled concurrent illness including, but not limited to:

    1. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
    2. Diarrhea of any cause ≥ CTCAE grade 2
    3. Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
    4. Any kind of malabsorption syndrome significantly affecting gastrointestinal function
  • Pregnant or nursing female patients. NOTE: If a female patient becomes pregnant or suspects that she is pregnant while participating in this study, she should stop taking study drug and immediately inform her treating physician immediately.
  • Prior therapy with a Hedgehog inhibitor
  • Unwillingness or inability to comply with procedures required in this protocol
  • Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
  • History of Congestive Heart Failure (CHF) or ventricular arrhythmia requiring medication.
  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: NCT01774253

Contacts
Contact: Genevieve Bergendahl, RN 616-267-0335 genevieve.bergendahl@helendevoschildrens.org
Contact: Alyssa VanderWerff (616) 267-0327 alyssa.vanderwerff@helendevoschildrens.org

Locations
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Sam Chimienti    602-546-0188    schimienti@phoenixchildrens.com   
Principal Investigator: Amy Rosenfeld, MD         
United States, Michigan
Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Shannon Mackeigan    616-267-1162    shannon.mackeigan@helendevoschildrens.org   
Principal Investigator: Albert Cornelius, MD         
Principal Investigator: Giselle Sholler, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Kate McCormack, RN    843-792-3379    mccormk@musc.edu   
Principal Investigator: Amy-Lee Bredlau, MD         
Sponsors and Collaborators
Giselle Sholler
Spectrum Health Hospitals
Phoenix Children's Hospital
Investigators
Study Chair: Giselle Sholler, MD The Spectrum Health Group
Principal Investigator: Albert Cornelius, MD Helen DeVos Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT01774253     History of Changes
Other Study ID Numbers: NMTRCPG007
Study First Received: January 18, 2013
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Spectrum Health Hospitals:
DIPG

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

ClinicalTrials.gov processed this record on August 18, 2014