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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

Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Disseminated Neuroblastoma; Ganglioneuroblastoma; Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Regional Neuroblastoma; Stage 4S Neuroblastoma

Intervention: cyclophosphamide (Drug); topotecan hydrochloride (Drug); cisplatin (Drug); etoposide phosphate (Drug); vincristine sulfate (Drug); doxorubicin hydrochloride (Drug); iobenguane I 131 (Radiation); therapeutic conventional surgery (Procedure); busulfan (Drug); melphalan (Drug); autologous hematopoietic stem cell transplantation (Procedure); in vitro-treated peripheral blood stem cell transplantation (Procedure); 3-dimensional conformal radiation therapy (Radiation); external beam radiation therapy (Radiation); intensity-modulated radiation therapy (Radiation); isotretinoin (Drug); pharmacological study (Other); questionnaire administration (Other); laboratory biomarker analysis (Other)

Phase: N/A

Status: Recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Brian Weiss, MD, Principal Investigator, Affiliation: Children's Oncology Group

Summary

This clinical trial is studying induction therapy followed by meta-iodobenzylguanidine (MIBG) labeled with iodine-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 MIBG labeled with iodine-131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as cisplatin, 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 can replace blood-forming cells that are damaged by MIBG labeled with iodine-131 and chemotherapy.

Clinical Details

Official title: A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG Followed by Myeloablative Busulfan/Melphalan (Bu/Mel) for Newly Diagnosed High-Risk Neuroblastoma

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Proportion of MIBG avid patients who are able to be treated with iobenguane I 131

Proportion of MIBG avid patients who are able to be treated with iobenguane I 131 and then Bu/Mel

Percentage of average per capita income encompassed by the total of travel + housing + lost wages

Proportion of eligible high-risk patients accrued to the study

Event-free survival rate

Secondary outcome:

Response rate, defined as the proportion of evaluable patients who attain a response of partial response or better at the end of iobenguane I 131 + Bu/Mel therapy and local radiotherapy

Incidence of adverse events and SOS, assessed by Common Terminology Criteria version 4.0 for toxicity assessment and grading

Detailed 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.

Eligibility

Minimum age: 1 Year. Maximum age: 30 Years. Gender(s): Both.

Criteria:

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

Locations and Contacts

Children's Hospital of Alabama, Birmingham, Alabama 35233, United States; Recruiting
Alyssa T. Reddy, Phone: 205-934-0309
Alyssa T. Reddy, Principal Investigator

University of Alabama at Birmingham, Birmingham, Alabama 35294, United States; Recruiting
Alyssa T. Reddy, Phone: 205-934-0309
Alyssa T. Reddy, Principal Investigator

Phoenix Childrens Hospital, Phoenix, Arizona 85016, United States; Recruiting
Jessica Boklan, Phone: 602-546-0920
Jessica Boklan, Principal Investigator

Children's Hospital Los Angeles, Los Angeles, California 90027, United States; Recruiting
Leo Mascarenhas, Phone: 323-361-4110
Leo Mascarenhas, Principal Investigator

University of California San Francisco Medical Center-Parnassus, San Francisco, California 94143, United States; Recruiting
Katherine K. Matthay, Phone: 877-827-3222
Katherine K. Matthay, Principal Investigator

Children's Hospital Colorado, Aurora, Colorado 80045, United States; Recruiting
Timothy P. Garrington, Phone: 720-777-6672
Timothy P. Garrington, Principal Investigator

Connecticut Children's Medical Center, Hartford, Connecticut 06106, United States; Recruiting
Michael S. Isakoff, Phone: 860-545-9981
Michael S. Isakoff, Principal Investigator

Children's National Medical Center, Washington, District of Columbia 20010, United States; Recruiting
Jeffrey S. Dome, Phone: 202-884-2549
Jeffrey S. Dome, Principal Investigator

University of Chicago, Chicago, Illinois 60637, United States; Recruiting
Susan L. Cohn, Phone: 773-834-7424
Susan L. Cohn, Principal Investigator

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Carlos Rodriguez-Galindo, Phone: 866-790-4500
Carlos Rodriguez-Galindo, Principal Investigator

C S Mott Children's Hospital, Ann Arbor, Michigan 48109, United States; Recruiting
Rajen Mody, Phone: 800-865-1125
Rajen Mody, Principal Investigator

University of North Carolina, Chapel Hill, North Carolina 27599, United States; Recruiting
Stuart H. Gold, Phone: 877-668-0683, Email: cancerclinicaltrials@med.unc.edu
Stuart H. Gold, Principal Investigator

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Susan G. Kreissman, Phone: 888-275-3853
Susan G. Kreissman, Principal Investigator

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States; Recruiting
Brian D. Weiss, Phone: 513-636-2799
Brian D. Weiss, Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Yael P. Mosse, Phone: 215-590-2810
Yael P. Mosse, Principal Investigator

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Jacqueline M. Kraveka, Phone: 843-792-9321
Jacqueline M. Kraveka, Principal Investigator

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States; Recruiting
Naomi J. Winick, Phone: 214-648-7097
Naomi J. Winick, Principal Investigator

Cook Children's Medical Center, Fort Worth, Texas 76104, United States; Terminated

Primary Children's Hospital, Salt Lake City, Utah 84113, United States; Recruiting
Phillip E. Barnette, Phone: 801-585-5270
Phillip E. Barnette, Principal Investigator

Seattle Children's Hospital, Seattle, Washington 98105, United States; Recruiting
Douglas S. Hawkins, Phone: 866-987-2000
Douglas S. Hawkins, Principal Investigator

Providence Sacred Heart Medical Center and Children's Hospital, Spokane, Washington 99204, United States; Recruiting
Judy L. Felgenhauer, Phone: 800-228-6618, Email: HopeBeginsHere@providence.org
Judy L. Felgenhauer, Principal Investigator

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States; Recruiting
Kenneth B. DeSantes, Phone: 608-262-5223
Kenneth B. DeSantes, Principal Investigator

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States; Recruiting
Meghen B. Browning, Phone: 414-805-4380
Meghen B. Browning, Principal Investigator

Additional Information

Starting date: October 2010
Last updated: February 23, 2015

Page last updated: August 23, 2015

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