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
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Neuroblastoma |
Drug: busulfan Drug: cisplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: irinotecan hydrochloride Drug: isotretinoin Drug: melphalan 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 Type: | Interventional |
| 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 ]
| Estimated Enrollment: | 44 |
| Study Start Date: | December 2011 |
| Estimated Primary Completion Date: | April 2012 (Final data collection date for primary outcome measure) |
Show Detailed Description
Eligibility| Ages Eligible for Study: | 1 Year to 30 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Diagnosis of neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites meeting 1 of the following staging criteria:
Newly diagnosed International Neuroblastoma Staging System (INSS) stage 4 disease meeting 1 of the following criteria:
- 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, or unknown
Newly diagnosed INSS stage 3 disease meeting 1 of the following criteria:
- 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
- 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
- Age ≥ 365 days initially diagnosed with INSS stage 1, 2, or 4S who progressed (within the past 4 weeks) to a stage 4 without interval chemotherapy
- No patients aged 12-18 months with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1)
- Must be enrolled onto ANBL00B1 biologic study
- Must have ≥ 1 "MIBG-avid target lesion" present on MIBG scan in the past 4 weeks
PATIENT CHARACTERISTICS:
- Total bilirubin ≤1.5 times upper limit of normal (ULN)
- AST or ALT ≤ 10 times ULN
Creatinine clearance or radioisotope GFR ≥ 70 mL/min 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)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by radionuclide evaluation
Able to tolerate peripheral blood stem cell (PBSC) collection
- No contraindications to PBSC collection including weight, size, or physical condition that would preclude apheresis
PRIOR CONCURRENT THERAPY:
No prior systemic therapy
- Localized emergency radiotherapy to sites of life-threatening or function-threatening disease and ≥ 1 measurable lesion is not irradiated
- No more than 1 course of chemotherapy per low- or intermediate-risk neuroblastoma therapy before determination of MYCN amplification and histology
No local radiotherapy that includes any of the following:
1,200 cGy to more than 33% of both kidneys
- Patient must have ≥ 1 kidney that has not exceeded the dose/volume of radiation listed
- 1,800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver
- No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
Contacts and Locations| 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 |
More Information
Additional Information:
No publications provided
| Responsible Party: | Gregory H. Reaman, Children's Oncology Group - Group Chair Office |
| ClinicalTrials.gov Identifier: | NCT01175356 History of Changes |
| Other Study ID Numbers: | CDR0000682629, COG-ANBL09P1 |
| Study First Received: | August 3, 2010 |
| Last Updated: | April 6, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
disseminated neuroblastoma localized resectable neuroblastoma localized unresectable neuroblastoma regional neuroblastoma stage 4S neuroblastoma |
Additional relevant MeSH terms:
|
Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Busulfan Cyclophosphamide Melphalan Etoposide phosphate Irinotecan |
Cisplatin Doxorubicin Etoposide Vincristine 3-Iodobenzylguanidine Camptothecin Topotecan Isotretinoin Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013