Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2011 by Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor:
Collaborator:
Brown University
Information provided by:
Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier:
NCT01088035
First received: March 16, 2010
Last updated: June 21, 2011
Last verified: June 2011
  Purpose

This is a phase II study evaluating the feasibility of concurrent carboplatin given with focal radiation therapy in children age 12 months to < 21 years with newly diagnosed localized ependymoma who have no or minimal residual disease post-operatively (< 0.5 cm). The hypothesis is that utilizing carboplatin as a radiosensitizer is feasible and tolerable and may improve event-free survival (EFS) and minimize local recurrences as compared to historic controls. Following a neurosurgical resection and staging, patients who meet the eligibility criteria will receive standard fractionated radiation therapy at doses of 54 to 59.4 Gy to the primary site depending upon age. All patients will receive 35 mg/m²/day of carboplatin prior to each fraction of radiotherapy. Although significant neutropenia is not anticipated, G-CSF will be administered per study guidelines during radiation if neutropenia occurs. All patients will be followed for toxicity, response (resolution of residual disease) and event-free survival (EFS). Patients' tumor sample, blood and cerebro-spinal fluid (CSF) will also be prospectively evaluated to quantify the level of Survivin, a known inhibitor of apoptosis, via immunohistochemistry, Western Blot Analysis (in tumor tissue) and ELISA (in blood and CSF). The feasibility of obtaining these levels prospectively and in real time will be evaluated.


Condition Intervention Phase
Ependymoma
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Multi-Institutional Trial of Focal Radiotherapy With Concomitant Carboplatin as a Radiosensitizer and the Prospective Analysis of Survivin, an Inhibitor of Apoptosis, as a Biomarker in Children With Newly Diagnosed Non-Metastatic Ependymoma and Minimal Residual Disease Post-Operatively

Resource links provided by NLM:


Further study details as provided by Ann & Robert H Lurie Children's Hospital of Chicago:

Primary Outcome Measures:
  • Measure the EFS of newly diagnosed non-metastatic ependymoma patients treated with a combination of daily carboplatin as a radiosensitizer and conformal radiotherapy. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Explore the tolerability, feasibility and toxicities associated with daily carboplatin as a radiosensitizer in patients with newly diagnosed non-metastatic ependymoma receiving focal fractionated radiotherapy. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Tolerability and toxicity will be measured by documenting the toxicities associated with this treatment using the current CTCAE version 4.0. The feasibility of this therapy will be measured by observing the ability to finish therapy without delays and the ability to receive daily carboplatin and radiation in the time alloted by the study (within 4 hours) on a daily basis. Delays in therapy will be documented in an effort to define both tolerability and feasibility.


Secondary Outcome Measures:
  • Explore the overall survival (OS) in patients with newly diagnosed non-metastatic ependymoma treated with this regimen. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Evaluate the feasibility of quantifying Survivin expression in primary ependymoma tumor, blood and CSF samples in a prospective fashion. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Explore trends or relationships between Survivin expression (in tumor, blood and CSF samples) and tumor histology. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Explore trends or relationships between Survivin expression (in tumor, blood and CSF samples) and patient responses. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Explore trends or relationships between Survivin expression (in tumor, blood and CSF samples) and survival outcomes. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Explore trends or relationships between Survivin expression (in tumor, blood and CSF samples) tumor recurrences. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: April 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carboplatin Drug: Carboplatin
Patients will receive daily carboplatin as a radiation sensitizer prior to radiation each day.

  Eligibility

Ages Eligible for Study:   12 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be enrolled before treatment begins.
  • Patients must be ≥ 12 months and < 22 years of age at the time of diagnosis.
  • The target tumors are primary brain non-metastatic (M0) ependymomas tumors. Patients must have histologic verification of an ependymoma at diagnosis. Patients with the following world health organization (WHO) diagnoses will be eligible for this study:Ependymoma (Subtypes: cellular, papillary, clear cell and tanycytic) and Anaplastic Ependymoma
  • Life expectancy of ≥ 8 weeks.
  • Newly diagnosed ependymoma and must not have had any prior chemotherapy or radiotherapy.
  • All patients must have:

    • A pre-operative MRI scan of the brain with and without contrast. NOTE: CT scans are NOT sufficient for study eligibility since radiation therapy planning and responses will be based on MRI scans only.
    • Post-operative head MRI scan with and without contrast (preferably within 72 hours post-operatively).
    • Spinal MRI (T-1 weighted imaging with and without gadolinium) is required within 28 days of surgery if done post-operatively and within 14 days of surgery if done pre-operatively. For posterior fossa tumors, pre-operative MRI scans are preferred because surgically induced inflammation/blood can be difficult to distinguish from tumor.
    • Lumbar CSF cytology examination obtained between 7 and 31 days following surgery.
    • Adequate bone marrow function, defined as:
    • Peripheral absolute neutrophil count (ANC) >1500/μL
    • Platelet count ≥ 100,000/μL (transfusion independent)
    • Hemoglobin ≥ 10.0 gm/dl (may receive RBC transfusions)
    • Adequate renal function defined as:
    • Serum creatinine < 1.5 times the upper limit of normal based on the patient's age, or creatinine clearance greater than 60 ml/min/1.73 m² corrected for age and body surface area.
    • Adequate liver function defined as:
    • Total bilirubin <1.5 x the institutional normal
    • SGOT (AST) or SGPT (ALT) <2.5 x institutional normals.
  • Patients must begin chemoradiotherapy within 56 days of definitive surgery.
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • Patients must provide assent as per local IRB guidelines (if applicable).
  • Patients and/or their families must consent to the mandatory biology studies, including serum Survivin levels, CSF Survivin levels, paraffin-embedded tissue and fresh-frozen tissue when available.
  • Karnofsky/Lansky scoring greater than 50.
  • Corticosteroid supportive care is permissible at the clinician's discretion prior to and during chemo-radiotherapy.
  • Anti-seizure medication support is permitted as necessary and at the treating physician's discretion.

Exclusion:

  • Prior chemotherapy or prior radiotherapy
  • Patients who are pregnant or breast feeding, or patients (male or female) not employing adequate contraception. Acceptable means of birth control include IUD, oral contraceptive, subdermal implant, a condom with a contraceptive sponge or suppository or abstinence.
  • Patients who are unable to undergo MR imaging
  • Patients with evidence of metastatic disease on spine MRI or CSF sampling
  • Patients with post-operative residual tumor > 0.5 cm, unless a repeat surgery is performed making the residual tumor less than 1.5 cm². Note: Timing for enrollment and initiation of therapy will begin after second surgery if a repeat surgery is performed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088035

Contacts
Contact: Kelly Verel 773-880-4000 ext 8147
Contact: Lauren Evans 773-880-4000 ext 8518

Locations
United States, Illinois
Children's Memorial Hospital Recruiting
Chicago, Illinois, United States, 60614
Contact: Kelly Verel    773-880-4000 ext 8147      
Contact: Lauren Evans    7738804000 ext 8518      
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Brown University
Investigators
Principal Investigator: Jason Fangusaro, MD Ann & Robert H Lurie Children's Hospital of Chicago
Principal Investigator: Rachel Altura, MD Brown University
  More Information

No publications provided

Responsible Party: Jason Fangusaro, Children's Memorial Hospital
ClinicalTrials.gov Identifier: NCT01088035     History of Changes
Other Study ID Numbers: CMH 09C4
Study First Received: March 16, 2010
Last Updated: June 21, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Ann & Robert H Lurie Children's Hospital of Chicago:
Childhood ependymoma
Ependymoma
Survivin

Additional relevant MeSH terms:
Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carboplatin
Radiation-Sensitizing Agents
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014