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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01175356
Other study ID # ANBL09P1
Secondary ID NCI-2011-01745AN
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date October 4, 2010
Est. completion date September 28, 2024

Study information

Verified date December 2023
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This pilot clinical trial studies 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 phosphate, 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. Giving radioisotope therapy, chemotherapy, and peripheral stem cell transplant may kill more tumor cells.


Description:

PRIMARY OBJECTIVE: I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131]) delivered after multi-agent chemotherapy, and b) post-induction busulfan/melphalan (Bu/Mel) consolidation therapy. SECONDARY OBJECTIVES: I. To assess the tolerability of treating high-risk neuroblastoma 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. TERTIARY OBJECTIVES: 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 fludeoxyglucose F-18 (18FDG)-positron emission tomography (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 relate exposure to SOS incidence. OUTLINE: 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 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 10-12 weeks from the date of iobenguane I 131 infusion, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1. 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 (2 dimensional [D], 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 99
Est. completion date September 28, 2024
Est. primary completion date September 28, 2016
Accepts healthy volunteers No
Gender All
Age group 1 Year to 30 Years
Eligibility Inclusion Criteria: - Patients have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [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 International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: - v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (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 deoxyribonucleic acid [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/1.73 m^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 x upper limit of normal (ULN) for age - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age - Shortening fraction >= 27% by echocardiogram 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 Exclusion Criteria: - 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 centigray (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

Study Design


Related Conditions & MeSH terms


Intervention

Radiation:
3-Dimensional Conformal Radiation Therapy
Undergo radiotherapy
Procedure:
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
Drug:
Busulfan
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Doxorubicin Hydrochloride
Given IV
Etoposide Phosphate
Given IV
Radiation:
External Beam Radiation Therapy
Undergo radiotherapy
Procedure:
In Vitro-Treated Peripheral Blood Stem Cell Transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
Radiation:
Intensity-Modulated Radiation Therapy
Undergo radiotherapy
Iobenguane I-131
Given IV
Drug:
Isotretinoin
Given PO
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Melphalan
Given IV
Other:
Pharmacological Study
Correlative studies
Questionnaire Administration
Ancillary studies
Procedure:
Therapeutic Conventional Surgery
Undergo surgery
Drug:
Topotecan Hydrochloride
Given IV
Vincristine Sulfate
Given IV

Locations

Country Name City State
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Children's Hospital of Alabama Birmingham Alabama
United States University of Alabama at Birmingham Cancer Center Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Duke University Medical Center Durham North Carolina
United States Cook Children's Medical Center Fort Worth Texas
United States Connecticut Children's Medical Center Hartford Connecticut
United States Children's Hospital Los Angeles Los Angeles California
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Children's Hospital of Wisconsin Milwaukee Wisconsin
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Phoenix Childrens Hospital Phoenix Arizona
United States Primary Children's Hospital Salt Lake City Utah
United States UCSF Medical Center-Mission Bay San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Seattle Children's Hospital Seattle Washington
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Children's National Medical Center Washington District of Columbia

Sponsors (2)

Lead Sponsor Collaborator
Children's Oncology Group National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131 Number of MIBG avid patients who receive 131I-MIBG divided by the number of patients evaluable for the feasibility of MIBG endpoint x 100%. Up to 6 weeks after course 5 of induction
Primary Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy Number of MIBG avid patients who receive 131I-MIBG and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint x 100%. Up to day -6 of conditioning
Secondary Incidence of Unacceptable Toxicity and Sinusoidal Obstruction Syndrome (SOS), Assessed by Common Terminology Criteria (CTV)v.4.0 for Toxicity Assessment and Grading for I-MIBG Number of patients who had an unacceptable toxicity or experienced SOS. Unacceptable toxicity was defined as CTC Grade 4-5 Pulmonary/Respiratory. Up to 6 weeks after course 5 of induction
See also
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Recruiting NCT00904241 - Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
Active, not recruiting NCT02311621 - Engineered Neuroblastoma Cellular Immunotherapy (ENCIT)-01 Phase 1
Recruiting NCT05192980 - SIOPEN BIOPORTAL, An International Registry Linked to a Virtual Biobank for Patients With Peripheral Neuroblastic Tumours N/A
Active, not recruiting NCT03126916 - Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL) Phase 3
Active, not recruiting NCT03786783 - Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Phase 2
Recruiting NCT02112617 - Phase II Study of Proton Radiation Therapy for Neuroblastoma N/A
Completed NCT01767194 - Irinotecan Hydrochloride and Temozolomide With Temsirolimus or Dinutuximab in Treating Younger Patients With Refractory or Relapsed Neuroblastoma Phase 2
Active, not recruiting NCT02176967 - Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma Phase 3
Active, not recruiting NCT01798004 - Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Phase 1