Brain CancerPhase 2NCT01012609
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
A Phase 2 study testing cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in people with Brain Cancer, run by Memorial Sloan Kettering Cancer Center at 12 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Brain Cancer
- What is being tested?
- cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 30 Oct 2009to 15 Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States11 sites
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, 30322
John Hopkins Medical Center
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
University of Colorado Health Sciences Center
Denver, Colorado
University of Florida
Gainesville, Florida
Md Anderson Cancer Center
Houston, Texas, 77030
Children's Mercy Hospital & Clinics
Kansas City, Missouri, 64108
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
MD Anderson Cancer Center Orlando at Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Phoenix Children'S Hospital
Phoenix, Arizona, 85016
Seattle Children'S Hospital
Seattle, Washington
About this study
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)
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
- Being tested
- cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan
- Keywords
- high-grade astrocytomas, newly diagnosed diffuse pontine tumors, External beam radiation therapy, cetuximab, irinotecan, POETIC
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecanOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival.
Measured: 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)
Measured: 2 years
Secondary outcomes (7)
Time to Progression
Measured: 2 years
Number of Participants Who Have Undergone Tumor Analysis
Participant tumor analysis for potential associations between primary tumor tissue molecular markers and tumor response.
Measured: 2 years
Number of Samples Demonstrating EGFR Copy Number Gain
Identify gene transcripts for putative cetuximab
Measured: 2 years
Number of Participant Tumors Analyzed for Potential Association Between Histology (Grade) With Protein and ELISA Measurements of Those Proteins.
Measured: 2 years
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.
Measured: 2 years
Event Free Survival
Measured: up to 12 months
Overall Survival
Measured: Up to 43 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2009 (estimated)
- Study start30 Oct 2009
- Primary completion15 Jan 2018
- Study completion15 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- 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, University of Florida
- Responsible party
- Sponsor
- Investigators
- Ira Dunkel, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01012609
- Sponsor's protocol ID
- 09-014
- Status last verified
- Mar 2022
- First submitted
- 11 Nov 2009
- Last updated
- 14 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01012609
- Acronym / sponsor ID
- 09-014
- Conditions
- Brain Cancer
- Keywords
- high-grade astrocytomas, newly diagnosed diffuse pontine tumors, External beam radiation therapy, cetuximab, irinotecan, POETIC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- 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, University of Florida
- Study start
- 30 Oct 2009 (actual)
- Primary completion
- 15 Jan 2018 (actual)
- Study completion
- 15 Jan 2018 (actual)
- First posted
- 13 Nov 2009 (estimated)
- Results
- Posted 30 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| pts with high-grade astrocytoma | Experimental | Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecanThis 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. |
| pts with diffuse pontine tumor | Experimental | Other: cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecanThis 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. |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecanExternal 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. | Other | pts with diffuse pontine tumor, pts with high-grade astrocytoma |
Primary outcome
Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival.
Time frame: 1 year
Number of Participants Experiencing Toxicity
Time frame: 2 years
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)
7 secondary outcomes
Time to Progression
Time frame: 2 years
Number of Participants Who Have Undergone Tumor Analysis
Time frame: 2 years
Number of Samples Demonstrating EGFR Copy Number Gain
Time frame: 2 years
Number of Participant Tumors Analyzed for Potential Association Between Histology (Grade) With Protein and ELISA Measurements of Those Proteins.
Time frame: 2 years
Percentage of Participants With Development of Rash, Either Acneiform and/or Desquamation
Time frame: 2 years
Event Free Survival
Time frame: up to 12 months
Overall Survival
Time frame: Up to 43 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ira Dunkel, MD principal investigator
Memorial Sloan Kettering Cancer Center
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab in conjunction with external beam radiation therapy, followed by cetuximab and irinotecan in people with Brain Cancer, run by Memorial Sloan Kettering Cancer Center at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With High-grade Astrocytoma and Diffuse Pontine Tumors Achieving One Year Progression Free Survival. (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2022; AzTrials last refreshed its copy on 8 Nov 2026.