Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin
RATIONALE: 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.
PURPOSE: 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.
Drug: doxorubicin hydrochloride
Drug: irinotecan hydrochloride
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Other: pharmacological study
Other: questionnaire administration
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Radiation: external beam radiation therapy
Radiation: intensity-modulated radiation therapy
Radiation: iobenguane I 131
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A COG Pilot Study of Intensive Induction Therapy and 131I-MIBG With Myeloablative Carboplatin, Etoposide and Melphalan (CEM) for Newly Diagnosed High-Risk Neuroblastoma|
- Proportion of patients treated with iodine I 131 meta-iodobenzylguanidine (131 I-MIBG), carboplatin, etoposide phosphate, and melphalan [ Designated as safety issue: No ]
- 1-year event-free survival rate [ Designated as safety issue: No ]
- Response rate [ Designated as safety issue: No ]
- Tumor burden [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Relationship of sinusoidal obstruction syndrome to dosages of myeloablative consolidation therapy and autologous stem cell rescue, and whole-body radiation dose or delay of radiation clearance due to 131 I-MIBG [ Designated as safety issue: No ]
|Study Start Date:||December 2011|
|Estimated Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
- 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)/irinotecan/vincristine delivered after multi-agent chemotherapy, and post-Induction busulfan/melphalan consolidation therapy.
- To assess the tolerability of these regimens in these patients.
- To assess the response rate of patients treated with these regimens.
- To describe the relationship of tumor norepinephrine transporter (hNET) expression with ^131I-MIBG uptake at diagnosis and immediately after ^131I-MIBG therapy, and tumor response.
- To assess the relative reliability of ^123 I-MIBG and 18FDG-PET imaging in assessment of tumor activity at diagnosis, after 2 courses of induction chemotherapy, before surgical resection and ^131I-MIBG.
- To compare detectable tumor burden before and immediate after therapy on the ^123I-MIBG diagnostic scan.
- To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to dosages of myeloablative consolidation therapy with busulfan/melphalan and whole-body radiation dose or delay of radiation clearance due to^131I-MIBG.
- To analyze busulfan first-dose pharmacokinetics as measured by area under the curve (AUC) and to relate exposure to SOS incidence.
- To describe the toxicity of ^131I-MIBG combined with vincristine and irinotecan given on a 5-day schedule.
OUTLINE: This is a pilot, multicenter study.
Induction chemotherapy: Patients receive 5 courses of induction therapy.
- Courses 1-2: Patients receive cyclophosphamide 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 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 (^131I-MIBG) 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 ùundergo 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 28-42 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 oral isotretinoin twice daily 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.
|United States, Alabama|
|UAB Comprehensive Cancer Center||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Contact: Clinical Trials Office - UAB Comprehensive Cancer Center 205-934-0309|
|United States, California|
|Childrens Hospital Los Angeles||Recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Leo Mascarenhas 323-361-2529|
|UCSF Helen Diller Family Comprehensive Cancer Center||Recruiting|
|San Francisco, California, United States, 94115|
|Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi 877-827-3222|
|United States, Colorado|
|Children's Hospital Colorado Center for Cancer and Blood Disorders||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Kelly W. Maloney 720-777-6673|
|United States, District of Columbia|
|Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010-2970|
|Contact: Clinical Trials Office - Children's National Medical Center 202-884-2549|
|United States, Illinois|
|University of Chicago Cancer Research Center||Recruiting|
|Chicago, Illinois, United States, 60637-1470|
|Contact: Clinical Trials Office - University of Chicago Cancer Research 773-834-7424|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229-3039|
|Contact: Clinical Trials Office - Cincinnati Children's Hospital Medica 513-636-2799|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Elizabeth Fox 267-425-3010|
|Principal Investigator:||Brian Weiss, MD||Children's Hospital Medical Center, Cincinnati|