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

Brain Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01012609
• Other study ID #: 09-014
• Status: Completed
• Phase: Phase 2
• Start date: October 30, 2009
• Est. completion date: January 15, 2018

Study information

• Verified date: March 2022
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: January 15, 2018
• Est. primary completion date: January 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Astrocytoma
• Brain Cancer
• Brain Neoplasms
• Brain Stem Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Canada	Alberta Children'S Hospital	Calgary	Alberta
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia
United States	John Hopkins Medical Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Md Anderson Cancer Center	Houston	Texas
United States	Children's Mercy Hospital & Clinics	Kansas City	Missouri
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children	Orlando	Florida
United States	Phoenix Children'S Hospital	Phoenix	Arizona
United States	Seattle Children'S Hospital	Seattle	Washington

Sponsors (11)

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

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival.		1 year
Primary	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	Time to Progression		2 years
Secondary	Number of Participants Who Have Undergone Tumor Analysis	Participant tumor analysis for potential associations between primary tumor tissue molecular markers and tumor response.	2 years
Secondary	Number of Samples Demonstrating EGFR Copy Number Gain	Identify gene transcripts for putative cetuximab	2 years
Secondary	Number of Participant Tumors Analyzed for Potential Association Between Histology (Grade) With Protein and ELISA Measurements of Those Proteins.		2 years
Secondary	Percentage of Participants With Development of Rash, Either Acneiform and/or Desquamation	The purpose is 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.	2 years
Secondary	Event Free Survival		up to 12 months
Secondary	Overall Survival		Up to 43 months

External Links

•   Memorial Sloan-Kettering Cancer Center