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

NCT01012609 | Completed Phase 2 Results

• 1 other identifier: 09-014
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

Brain Cancer

Keywords

high-grade astrocytomas; newly diagnosed diffuse pontine tumors; External beam radiation therapy; cetuximab; irinotecan; POETIC

Outcome Measures

Primary Outcomes (2)

• Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival.

  1 year

• Number of Participants Experiencing Toxicity

  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, toxicities will be assessed via the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 3.0)

  2 years

Secondary Outcomes (7)

• Time to Progression

  2 years

• Number of Participants Who Have Undergone Tumor Analysis

  2 years

• Number of Samples Demonstrating EGFR Copy Number Gain

  2 years

• Number of Participant Tumors Analyzed for Potential Association Between Histology (Grade) With Protein and ELISA Measurements of Those Proteins.

  2 years

• Percentage of Participants With Development of Rash, Either Acneiform and/or Desquamation

  2 years

Study Arms (2)

pts with high-grade astrocytoma

EXPERIMENTAL

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

pts with diffuse pontine tumor

EXPERIMENTAL

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

Interventions

cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan OTHER

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.

pts with diffuse pontine tumor; pts with high-grade astrocytoma

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Children's Healthcare of Atlanta: collaborator
• Dana-Farber Cancer Institute: collaborator
• M.D. Anderson Cancer Center: collaborator
• Phoenix Children's Hospital: collaborator
• Alberta Children's Hospital: collaborator
• University of Colorado, Denver: collaborator
• Seattle Children's Hospital: collaborator
• Johns Hopkins University: collaborator
• Children's Mercy Hospital Kansas City: collaborator
• University of Florida: collaborator

Study Sites (12)

Phoenix Children'S Hospital

Phoenix, Arizona, 85016, United States

Location

University of Colorado Health Sciences Center

Denver, Colorado, United States

Location

University of Florida

Gainesville, Florida, United States

Location

MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

John Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Children's Mercy Hospital & Clinics

Kansas City, Missouri, 64108, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children'S Hospital

Seattle, Washington, United States

Location

Alberta Children'S Hospital

Calgary, Alberta, T2N 1N4, Canada

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Cetuximab; Irinotecan

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Ira Dunkel, MD
• Organization: Memorial Sloan Kettering Cancer Center

dunkeli@mskcc.org

212-639-2153

Study Officials

• Ira Dunkel, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2009
• First Posted: November 13, 2009
• Study Start: October 30, 2009
• Primary Completion: January 15, 2018
• Study Completion: January 15, 2018
• Last Updated: March 14, 2022
• Results First Posted: March 30, 2021

Record last verified: 2022-03

Locations

US (11); CA (1)