Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
| Status: | Completed |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 21 |
| Updated: | 2/8/2015 |
| Start Date: | April 2010 |
| End Date: | April 2015 |
| Contact: | Kelly Verel |
| Phone: | 773-880-4000 |
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
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.
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.
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.
We found this trial at
1
site
225 E Chicago Ave
Chicago, Illinois 60611
Chicago, Illinois 60611
(312) 227-4000
Ann & Robert H. Lurie Children's Hospital of Chicago Ann & Robert H. Lurie Children
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