External Beam Radiation Therapy and Cetuximab Followed by Irinotecan and Cetuximab for Children and Young Adults With Newly Diagnosed Diffuse Pontine Tumors and High-Grade Astrocytomas
Information source: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Brain Cancer
Intervention: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan (Other)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Memorial Sloan Kettering Cancer Center Official(s) and/or principal investigator(s): Ira Dunkel, MD, Principal Investigator, Affiliation: Memorial Sloan Kettering Cancer Center
Summary
Standard treatment for patients with diffuse pontine tumors is radiation therapy, but less
than 10% of patients are cured. Adding standard chemotherapy has not improved the cure rate.
Standard treatment for high-grade astrocytomas is surgery and radiation. The surgeon removes
as much of the tumor as she or he can. Radiation after that tries to kill any cancer cells
that are left. Some patients also get chemotherapy. These are anti-cancer drugs. They can be
given during or after radiation. Current standard treatments do not cure many patients.
In this study the doctors are adding a new medication called cetuximab to the treatment and
will also use a chemotherapy medication (irinotecan) that has been promising for patients
treated for recurrent disease.
Clinical Details
Official title: A Phase II Trial of External Beam Radiation Therapy and Cetuximab Followed by Irinotecan and Cetuximab for Children and Young Adults With Newly Diagnosed Diffuse Pontine Tumors and High-Grade Astrocytomas (POE08-01)
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To determine the proportion of patients with high-grade astrocytoma and diffuse pontine tumors achieving one year progression free survival.To determine the safety of cetuximab administered weekly in conjunction with involved field external beam radiation therapy for diffuse pontine tumors and high-grade astrocytomas.
Secondary outcome: To estimate the response rate, time to progression, and overall survival in 2 cohorts of patients (diffuse intrinsic pontine tumors, high-grade astrocytomas) treated on this protocol.To explore whether there are any potential associations between primary tumor tissue molecular markers and tumor response. Identify CSF protein markers that might indicate the presence of a brain tumor, to validate proteomic methodology by correlating protein & ELISA measurements of known proteins implicated in angiogenesis & tumor progression (VEGF, bFGF, SPARC, attractin) To explore whether there are any potential associations between histology (grade) with protein and ELISA measurements of those proteins. To investigate whether the rash associated with cetuximab is secondary to an inflammatory pathway initiated and mediated by the action of cetuximab on host cells.
Eligibility
Minimum age: 3 Years.
Maximum age: 21 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients must have either (1) histologic proof of a high-grade astrocytoma reviewed
by a POETIC institutional pathologist or (2) a radiological diagnosis via MRI scan of
a typical diffuse pontine tumor made by a POETIC institutional neuroradiologist.
Patients with a radiological diagnosis via MRI scan of a typical diffuse pontine
tumor will be enrolled on the diffuse pontine tumor arm of the study regardless of
histology in cases that are biopsied. Note: For collaborating non-POETIC
institutions, the reviews may be done by an institutional
pathologist/neuroradiologist.
- Patients must begin study prescribed therapy within 42 days of neurosurgical
resection or biopsy of the tumor (high-grade astrocytoma patients) or radiological
diagnosis (diffuse pontine tumor patients).
- Age ≥ 3-years and < 22-years-old.
- Brain MRI (and any other studies done according to clinical indications) must not
show any definitive evidence of leptomeningeal or extra-neural metastases.
- ANC ≥ 1000/μL and platelet count ≥ 100,000/μL
- Patients must have adequate organ function as defined by:
- Hepatic: total bilirubin < 1. 5 mg/dl, AST ≤ 2. 5 x the upper limit of normal.
- Renal: serum creatinine ≤ 1. 5 x the upper limit of normal for age, or calculated
creatinine clearance or nuclear GFR ≥ 70 ml/min/1. 73 m2.
- The patient, or for minors, a parent or legal guardian, must give informed written
consent indicating they are aware of the investigational nature of this study.
Exclusion Criteria:
- Evidence of leptomeningeal or extra-neural metastatic disease.
- Prior radiation therapy or chemotherapy
- Pregnancy, mothers unwilling to refrain from breast-feeding, and sexually mature
patients unwilling to practice an effective form of birth control.
- Other significant concomitant medical illnesses that would compromise the patient's
ability to receive all prescribed study therapy.
- Prior therapy which specifically and directly targets the EGFR pathway.
- Prior severe infusion reaction to a monoclonal antibody.
- Significant history of uncontrolled cardiac disease; i. e., uncontrolled hypertension,
unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
congestive heart failure, and cardiomyopathy with decreased ejection fraction.
- Patients with known Gilbert's Syndrome.
Locations and Contacts
Alberta Children'S Hospital, Calgary, Alberta T2N 1N4, Canada
Phoenix Children'S Hospital, Phoenix, Arizona 85016, United States
University of Colorado Health Sciences Center, Denver, Colorado, United States
University of Florida, Gainesville, Florida, United States
MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children, Orlando, Florida 32806, United States
Children's Healthcare of Atlanta at Egleston, Atlanta, Georgia 30322, United States
John Hopkins Medical Center, Baltimore, Maryland 21287, United States
Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
Children's Mercy Hospital & Clinics, Kansas City, Missouri 64108, United States
Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States
Md Anderson Cancer Center, Houston, Texas 77030, United States
Seattle Children'S Hospital, Seattle, Washington, United States
Additional Information
Memorial Sloan-Kettering Cancer Center
Starting date: November 2009
Last updated: September 30, 2014
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