Overview

This trial is active, not recruiting.

Condition brain cancer
Treatment cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
Phase phase 2
Sponsor Memorial Sloan Kettering Cancer Center
Collaborator Children's Healthcare of Atlanta
Start date November 2009
End date November 2016
Trial size 51 participants
Trial identifier NCT01012609, 09-014

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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.
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)
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.
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.

Primary Outcomes

Measure
To determine the proportion of patients with high-grade astrocytoma and diffuse pontine tumors achieving one year progression free survival.
time frame: 1 year
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

Secondary Outcomes

Measure
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
To explore whether there are any potential associations between primary tumor tissue molecular markers and tumor response.
time frame: 2 years
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
To explore whether there are any potential associations between histology (grade) with protein and ELISA measurements of those proteins.
time frame: 2 years
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

Eligibility Criteria

Male or female participants from 3 years up to 21 years old.

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.

Additional Information

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)
Principal investigator Ira Dunkel, MD
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center.