|No phase specified||Biomarker/Laboratory analysis, Treatment||Active||1 to 30||NCI, Other||ANBL09P1|
NCI-2011-01745, CDR0000682629, U10CA098543, COG-ANBL09P1, NCT01175356
This clinical trial is studying induction therapy followed by iobenguane I 131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin. Radioisotope therapy, such as iobenguane I 131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as carboplatin, etoposide, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that are destroyed by iobenguane I 131 and chemotherapy.
Further Study Information
I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days to 30 years, with an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131])/irinotecan/vincristine delivered after multi-agent chemotherapy, and post-Induction busulfan/melphalan (Bu/Mel) consolidation therapy.
I. To assess the tolerability of these regimens in these patients, age 365 days - 30 years, with a) an Induction block of 131I-MIBG therapy delivered after multi-agent chemotherapy, and b) the tolerability of receiving post-Induction Bu/Mel Consolidation therapy with autologous stem-cell rescue (ASCR), and local radiation therapy.
I. To assess the response rate after a regimen of Induction chemotherapy and 131I-MIBG and after a consolidation regimen of Bu/Mel with ASCR and local radiation therapy.
II. To describe the relationship of tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at diagnosis as well as with tumor response.
III. To assess the relative reliability of 123 I-MIBG and 18FDG-PET imaging in assessment of tumor activity at diagnosis, and prior to surgical resection.
IV. To compare detectable tumor burden on the pre-surgical resection radioiodinated -MIBG diagnostic scan and the immediate post-MIBG therapy 131I-MIBG scan.
V. To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to Bu/Mel or to whole-body radiation dose or delayed radiation clearance due to 131I-MIBG.
VI. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and to relate exposure to SOS incidence.
OUTLINE: This is a pilot, multicenter study.
INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy.
Courses 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Patients undergo peripheral blood stem cell (PBSC) collection after course 2.
Course 3 and 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3. Patients undergo surgery to remove remaining tumor following course 5.
Course 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2 and vincristine sulfate IV over 1 minute and doxorubicin hydrochloride IV over 24 hours on days 1-3.
Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease proceed to iobenguane I 131 induction therapy beginning 3-6 weeks after course 5. Patients receive vincristine IV on day 0, irinotecan IV over 90 minutes on day 0-4, and iobenguane I 131 IV over 90-120 minutes on day 1.
SURGERY: Patients undergo surgery after course 4 or before consolidation therapy.
CONSOLIDATION THERAPY: Within 4-6 weeks after completion of induction therapy, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1. Patients also complete a questionnaire regarding costs for travel and accommodations during therapy. Blood samples maybe collected after the first dose of busulfan for pharmacokinetic assays.
AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0.
RADIOTHERAPY: Beginning no sooner than 42 days after peripheral blood stem cell infusion, patients undergo 12 fractions of external-beam radiotherapy (2D, 3D-conformal, or intensity-modulated) to all areas of residual disease, primary tumor site, and involved nodal disease.
MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for 6 courses.
After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.
- Patients have a diagnosis of neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:
- Patients with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following:
- MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days regardless of additional biologic features
- Age > 18 months (> 547 days) regardless of biologic features
- Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown
- Patients with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following:
- MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), and age >= 365 days, regardless of additional biologic features
- Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
- Patients with newly diagnosed INSS Stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days, regardless of additional biologic features
- Patients >= 365 days initially diagnosed with: INSS Stage 1, 2, 4S who progressed to a Stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to Stage 4 for INSS Stage 1, 2, 4S
- Patients must have had no prior systemic therapy except for localized emergency radiation to sites of life- threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per Low- or Intermediate-Risk neuroblastoma therapy (P9641, A3961, ANBL0531) prior to determination of MYCN amplification and histology
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73m^2 OR serum creatinine based on age and/or gender as follows:
- =< 0.6 mg/dL (1 to < 2 years of age)
- =< 0.8 mg/dL (2 to < 6 years of age)
- =< 1.0 mg/dL (6 to < 10 years of age)
- =< 1.2 mg/dL (10 to < 13 years of age)
- =< 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- =< 1.7 mg/dL (male) or 1.4 mg/dL (female) ( >= 16 years of age)
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 times ULN for age
- Shortening fraction >= 27% by echocardiogram (ECHO) or
- Ejection fraction >= 50% by radionuclide evaluation
- No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
- Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method
- Female patients who are lactating must agree to stop breast-feeding
- Patients that are 12-18 months of age with INSS Stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible
- Patients are not eligible if they have received local radiation which includes any of the following: 1200 cGy to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria
Trial Lead Organizations/Sponsors
Children's Oncology GroupNational Cancer Institute
|Brian Weiss, MD||Principal Investigator|
|Children's Hospital of Alabama at University of Alabama at Birmingham|
|Alyssa T Reddy||Ph: 205-934-0309|
|UAB Comprehensive Cancer Center|
|Alyssa T Reddy||Ph: 205-934-0309|
|Phoenix Children's Hospital|
|Jessica Boklan||Ph: 602-546-0920|
|Children's Hospital Los Angeles|
|Leo Mascarenhas||Ph: 323-361-4110|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|Katherine K Matthay||Ph: 877-827-3222|
|Children's Hospital Colorado Center for Cancer and Blood Disorders|
|Timothy P Garrington||Ph: 720-777-6672|
|Connecticut Children's Medical Center|
|Michael S Isakoff||Ph: 860-545-9981|
|District of Columbia|
|Children's National Medical Center|
|Jeffrey S Dome||Ph: 202-884-2549|
|University of Chicago Cancer Research Center|
|Susan L Cohn||Ph: 773-834-7424|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute|
|Carlos Rodriguez-Galindo||Ph: 866-790-4500|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Stuart H Gold||Ph: 877-668-0683|
|Duke Cancer Institute|
|Susan G Kreissman||Ph: 888-275-3853|
|Cincinnati Children's Hospital Medical Center|
|Brian D Weiss||Ph: 513-636-2799|
|Children's Hospital of Philadelphia|
|Yael P. Mosse||Ph: 215-590-2810|
|Hollings Cancer Center at Medical University of South Carolina|
|Jacqueline M Kraveka||Ph: 843-792-9321|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas|
|Naomi J Winick||Ph: 214-648-7097|
|Cook Children's Medical Center - Fort Worth|
|Mary Meaghan P Granger||Ph: 682-885-2103|
|Salt Lake City|
|Primary Children's Medical Center|
|Phillip E Barnette||Ph: 801-585-5270|
|Children's Hospital and Regional Medical Center - Seattle|
|Douglas S Hawkins||Ph: 866-987-2000|
|Providence Cancer Center at Sacred Heart Medical Center|
|Judy L Felgenhauer||Ph: 800-228-6618|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Kenneth B DeSantes||Ph: 608-262-5223|
|Midwest Children's Cancer Center at Children's Hospital of Wisconsin|
|Meghen B Browning||Ph: 414-805-4380|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01175356
ClinicalTrials.gov processed this data on March 03, 2014
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