- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01774253
Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma
A Phase II, Open-label, Multi-center Study of Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine Glioma.
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.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Phoenix, Arizona, United States, 85016
- Phoenix Children's Hospital
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Michigan
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Grand Rapids, Michigan, United States, 49503
- Helen DeVos Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
- Bilirubin ≤ 1.5 times upper limit of normal
- 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:
- Granulocyte ≥ 1500 cells/mm3
- Platelet count ≥ 100,000 (plt/mm3)
- Serum albumin ≥ 2.5 g/dL
Urinalysis:
a. No clinically significant abnormalities
Acceptable coagulation status as defined by:
- PT/INR less than 1.5
- 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:
- Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
- Diarrhea of any cause ≥ CTCAE grade 2
- Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Days Participants Experienced Progression Free Survival (PFS)
Time Frame: 5 years
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Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.
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5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: 2 years
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To determine the safety and tolerability of Vismodegib as a single agent in pediatric and young adult patients with refractory or recurrent pontine glioma
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2 years
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Determine the Median Overall Survival (OS) of Participants
Time Frame: 2 years
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Overall Survival (OS) and clinical benefit (ORR + stable disease, SD)
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2 years
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Evaluate the Impact of Quality of Life of Children Receiving Vismodegib Using PedsQL Questionnaires
Time Frame: 2 years
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Evaluate the impact of Quality of Life of children receiving Vismodegib using PedsQL questionnaires
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2 years
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Determine the Response Rates of Participants Based on Activation (or no Activation) of Their Hedgehog Signaling Pathway
Time Frame: 3 years
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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
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3 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Albert Cornelius, MD, Helen DeVos Children's Hospital
- Study Chair: Giselle Sholler, MD, Beat Childhood Cancer at Atrium Health
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NMTRCPG007
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pontine Glioma
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National Cancer Institute (NCI)RecruitingRecurrent Malignant Glioma | Recurrent Medulloblastoma | Refractory Malignant Glioma | Refractory Medulloblastoma | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Primary Central Nervous System Neoplasm | Refractory Primary Central Nervous System Neoplasm | Refractory Diffuse Intrinsic Pontine...United States, Canada
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Ralph NULL SalloumChildren's Hospital Medical Center, CincinnatiRecruitingHigh Grade Glioma | Medulloblastoma | Meningioma | Anaplastic Ependymoma | Recurrent Malignant Glioma | Recurrent Medulloblastoma | Refractory Malignant Glioma | Refractory Medulloblastoma | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Primary Central Nervous System Neoplasm | Refractory Primary... and other conditionsUnited States
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Burzynski Research InstituteSuspendedDiffuse, Intrinsic Pontine GliomaUnited States
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University of California, San FranciscoTranslational Genomics Research InstituteCompletedDiffuse Intrinsic Pontine Glioma (DIPG)United States
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Rigshospitalet, DenmarkKarolinska University Hospital; Aarhus University Hospital; Sahlgrenska University... and other collaboratorsNot yet recruitingDiffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma, H3 K27M-Mutant | Diffuse Glioma | Pontine Tumors | Brain Tumor, Pediatric | Thalamic Tumor
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Cheng-Chia (Fred) WuFocused Ultrasound FoundationActive, not recruitingDiffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma, H3 K27M-Mutant | Diffuse Pontine and Thalamic GliomasUnited States
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University of FloridaAccelerate Brain Cancer Cure; Lyla Nsouli FoundationActive, not recruitingBrain Stem Glioma | Diffuse Intrinsic Pontine Glioma (DIPG)United States
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Sidney Kimmel Comprehensive Cancer Center at Johns...Solving Kids' CancerCompletedDiffuse Intrinsic Pontine Glioma (DIPG)United States
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University of California, San FranciscoNational Institute of Neurological Disorders and Stroke (NINDS); The Chad-Tough... and other collaboratorsRecruitingDiffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma, H3 K27M-Mutant | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Diffuse Midline Glioma, H3 K27M-Mutant | Recurrent WHO Grade III Glioma | WHO Grade III GliomaUnited States, Israel, Australia, Netherlands, Switzerland, New Zealand
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Pediatric Brain Tumor ConsortiumNational Cancer Institute (NCI)CompletedMalignant Glioma | Recurrent Childhood Ependymoma | Recurrent Medulloblastoma | Recurrent Diffuse Intrinsic Pontine Glioma | Recurrent Atypical Teratoid/Rhabdoid Tumor | Refractory Diffuse Intrinsic Pontine Glioma | CNS Embryonal Tumor, Not Otherwise SpecifiedUnited States
Clinical Trials on Vismodegib
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Genentech, Inc.Completed
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University of Michigan Rogel Cancer CenterCompletedCarcinoma, Basal CellUnited States
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Genentech, Inc.Completed
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Hoffmann-La RocheCompletedBasal Cell CarcinomaItaly, Czechia, Hungary, Belgium, Canada, Ireland, Mexico, Portugal, Slovenia, Spain, Turkey, Brazil, Bosnia and Herzegovina, Romania, United Kingdom, Germany, Israel, France, Greece, Russian Federation, Lithuania, Netherlands, Norway, Colomb... and more
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Sidney Kimmel Comprehensive Cancer Center at Johns...CompletedProstate CancerUnited States
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SRH Wald-Klinikum Gera GmbHCompletedBasal Cell CarcinomaGermany
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University Hospital, LilleHoffmann-La RocheCompletedBasal Cell CarcinomaFrance
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University of ArizonaGenentech, Inc.CompletedBasal Cell CarcinomaUnited States
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Hoffmann-La RocheTerminatedBasal Cell CarcinomaUnited States
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Hoffmann-La RocheWithdrawnIdiopathic Pulmonary Fibrosis