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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Children's Healthcare of Atlanta
Dana-Farber Cancer Institute
M.D. Anderson Cancer Center
Phoenix Children's Hospital
Alberta Children's Hospital
University of Colorado, Denver
Seattle Children's Hospital
Johns Hopkins University
Children's Mercy Hospital-Kansas City, MO
Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando
University of Florida
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01012609
First received: November 11, 2009
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Brain Cancer
Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the proportion of patients with high-grade astrocytoma and diffuse pontine tumors achieving one year progression free survival. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To explore whether there are any potential associations between primary tumor tissue molecular markers and tumor response. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To explore whether there are any potential associations between histology (grade) with protein and ELISA measurements of those proteins. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 51
Study Start Date: November 2009
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pts with high-grade astrocytoma
This is a 2-group parallel (high-grade astrocytoma, diffuse pontine tumor), single stage study investigating cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in pediatric and young adult patients. Optional exploratory components of the study include (1) correlation of tumor molecular markers with outcome, (2) CSF proteomics, and (3) assay of serum cytokine levels in patients who develop a cetuximab-associated rash.
Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
External beam radiation therapy (5940 cGy in 180 cGy fractions) with weekly cetuximab (250 mg/m2/dose).4-8 weeks rest, 10 cycles of irinotecan (16 mg/m2/day x 5 consecutive days x 2 weeks) with weekly cetuximab (250 mg/m2/dose) at about 21 day intervals. Research biological evaluations will be performed in consenting patients as an optional portion of the study. Cetuximab is to be given every 7 days (+/- 2 days). Cetuximab does not need to be given on Day 1 of each week.
Experimental: pts with diffuse pontine tumor
This is a 2-group parallel (high-grade astrocytoma, diffuse pontine tumor), single stage study investigating cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in pediatric and young adult patients. Optional exploratory components of the study include (1) correlation of tumor molecular markers with outcome, (2) CSF proteomics, and (3) assay of serum cytokine levels in patients who develop a cetuximab-associated rash.
Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
External beam radiation therapy (5940 cGy in 180 cGy fractions) with weekly cetuximab (250 mg/m2/dose).4-8 weeks rest, 10 cycles of irinotecan (16 mg/m2/day x 5 consecutive days x 2 weeks) with weekly cetuximab (250 mg/m2/dose) at about 21 day intervals. Research biological evaluations will be performed in consenting patients as an optional portion of the study. Cetuximab is to be given every 7 days (+/- 2 days). Cetuximab does not need to be given on Day 1 of each week.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01012609

Locations
United States, Arizona
Phoenix Children'S Hospital
Phoenix, Arizona, United States, 85016
United States, Colorado
University of Colorado Health Sciences Center
Denver, Colorado, United States
United States, Florida
University of Florida
Gainesville, Florida, United States
MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children
Orlando, Florida, United States, 32806
United States, Georgia
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, United States, 30322
United States, Maryland
John Hopkins Medical Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Missouri
Children's Mercy Hospital & Clinics
Kansas City, Missouri, United States, 64108
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
Md Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Children'S Hospital
Seattle, Washington, United States
Canada, Alberta
Alberta Children'S Hospital
Calgary, Alberta, Canada, T2N 1N4
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Children's Healthcare of Atlanta
Dana-Farber Cancer Institute
M.D. Anderson Cancer Center
Phoenix Children's Hospital
Alberta Children's Hospital
University of Colorado, Denver
Seattle Children's Hospital
Johns Hopkins University
Children's Mercy Hospital-Kansas City, MO
Arnold Palmer Hospital for Children/MD Anderson Cancer Center Orlando
University of Florida
Investigators
Principal Investigator: Ira Dunkel, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01012609     History of Changes
Other Study ID Numbers: 09-014
Study First Received: November 11, 2009
Last Updated: September 27, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
high-grade astrocytomas
newly diagnosed diffuse pontine tumors
External beam radiation therapy
cetuximab
irinotecan
POETIC

Additional relevant MeSH terms:
Astrocytoma
Brain Neoplasms
Brain Stem Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Infratentorial Neoplasms
Irinotecan
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014