Clinical trial NCT01012609: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Cancer
Keywords: high-grade astrocytomas
newly diagnosed diffuse pontine tumors
External beam radiation therapy
cetuximab
irinotecan
POETIC
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Children's Healthcare of Atlanta
name: Dana-Farber Cancer Institute
name: M.D. Anderson Cancer Center
name: Phoenix Children's Hospital
name: Alberta Children's Hospital
name: University of Colorado, Denver
name: Seattle Children's Hospital
name: Johns Hopkins University
name: Children's Mercy Hospital Kansas City
name: University of Florida
First posted: 2009-11-13
Enrollment: 47
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival.
timeFrame: 1 year
measure: Number of Participants Experiencing Toxicity
timeFrame: 2 years
Secondary outcomes:
measure: Time to Progression
timeFrame: 2 years
measure: Number of Participants Who Have Undergone Tumor Analysis
timeFrame: 2 years
measure: Number of Samples Demonstrating EGFR Copy Number Gain
timeFrame: 2 years
measure: Number of Participant Tumors Analyzed for Potential Association Between Histology (Grade) With Protein and ELISA Measurements of Those Proteins.
timeFrame: 2 years
measure: Percentage of Participants With Development of Rash, Either Acneiform and/or Desquamation
timeFrame: 2 years
measure: Event Free Survival
timeFrame: up to 12 months
measure: Overall Survival
timeFrame: Up to 43 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children'S Hospital
state: Arizona
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
city: Baltimore
country: United States
facility: John Hopkins Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital & Clinics
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children'S Hospital
state: Washington
city: Calgary
country: Canada
facility: Alberta Children'S Hospital
state: Alberta
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ira Dunkel, MD
role: PRINCIPAL_INVESTIGATOR
References: