Induction Chemotherapy Using Cyclophosphamide and Topotecan in Treating Patients Who Are Undergoing Autologous Peripheral Stem Cell Transplantation for Newly Diagnosed or Progressive Neuroblastoma

NCT00070200 | Completed Phase 1 DMC

• 3 other identifiers: ANBL02P1CDR0000330140COG-ANBL02P1
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 6

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan and cyclophosphamide, use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of induction chemotherapy using cyclophosphamide and topotecan in treating patients who are undergoing surgery and autologous stem cell transplantation followed by radiation therapy for newly diagnosed or progressive neuroblastoma.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma; stage 4S neuroblastoma; localized unresectable neuroblastoma; localized resectable neuroblastoma; regional neuroblastoma; disseminated neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who are classified as a "success"

  Given that the documented delivered dose intensity of chemotherapy in current induction regimens is 75-85% of the intended dose intensity,5,78 we shall consider an individual patient as a "success" in terms of feasibility if the patient is able to receive 75% or more of the intended chemotherapy doses of known active agents.

  Length of study

Secondary Outcomes (5)

• Number of toxic deaths

  Length of study

• Proportion of patients with dose limiting toxicities during induction cycle 1 and 2

  Length of study

• Tumor contamination of PBSCs

  Length of study

• Inability to adequately mobilize PBSCs

  Length of study

• Assessment of response

  Length of study

Study Arms (1)

All patients

EXPERIMENTAL

Induction Cycles 1 and 2 (CT) (21 days each), Cyclophosphamide (Days 1 thru 5) weight based dosage (\> 12 kg 400 mg/m2/day, \< 12 kg 13.3 mg/kg/day, \< 2 years old N/A. Topotecan (Days 1 thru 5) weight based dosage (\> 12 kg 1.2 mg/m2/day, \< 12 kg 0.04 mg/kg/day, \< 2 years old 0.04 mg/kg/day). Filgrastim (Days 6 →) weight based dosage (\> 12 kg 5 micrograms/kg, \< 12 kg 5 micrograms /kg, \< 2 years old 5 micrograms /kg.

Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: isotretinoin; Drug: melphalan; Drug: topotecan hydrochloride; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

filgrastim BIOLOGICAL

All patients

cisplatin DRUG

All patients

cyclophosphamide DRUG

All patients

doxorubicin hydrochloride DRUG

All patients

etoposide DRUG

All patients

isotretinoin DRUG

All patients

melphalan DRUG

All patients

topotecan hydrochloride DRUG

All patients

vincristine sulfate DRUG

All patients

conventional surgery PROCEDURE

All patients

peripheral blood stem cell transplantation PROCEDURE

All patients

radiation therapy RADIATION

All patients

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed neuroblastoma or ganglioneuroblastoma meeting 1 of the following staging criteria: * Newly diagnosed disease, at least 1 year of age, and meets criteria for 1 of the following: * International Neuroblastoma Staging System (INSS) stage 2a/2b with MYCN amplification (greater than 10) AND unfavorable pathology * INSS stage 3 with MYCN amplification OR unfavorable pathology * Newly diagnosed INSS stage 4 disease meeting criteria for 1 of the following: * Over 18 months of age * Age 12 to 18 months with any unfavorable biologic feature (MYCN amplification, unfavorable pathology, and/or DNA index=1) or any biologic feature that is indeterminant, unsatisfactory, or unknown * No INSS stage 4 disease and age 12 to 18 months with all 3 favorable biologic features (i.e., nonamplified MYCN, favorable pathology, and DNA index greater than 1) * Newly diagnosed INSS stage 3, 4, or 4S disease AND under 1 year of age with MYCN amplification * At least 1 year of age and initially diagnosed with INSS stage 1, 2, or 4S disease that progressed to stage 4 without interval chemotherapy * Must have been enrolled on COG-ANBL00B1 at initial diagnosis PATIENT CHARACTERISTICS: Age * 30 and under at initial diagnosis Performance status * Not specified Life expectancy * Not specified Hematopoietic * Absolute neutrophil count at least 1,000/mm\^3\* * Platelet count at least 100,000/mm\^3\* (transfusion independent) * Hemoglobin at least 10.0 g/dL\* (red blood cell transfusions allowed) NOTE: \*Granulocytopenia, anemia, and/or thrombocytopenia allowed for patients with tumor metastatic to the bone marrow Hepatic * Bilirubin no greater than 1.5 mg/dL * ALT less than 300 IU/L Renal * Creatinine no greater than 1.5 mg/dL * Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min Cardiovascular * ECG normal * Shortening fraction at least 27% by echocardiogram OR * Ejection fraction at least 50% by MUGA Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * No more than 1 prior chemotherapy course on the low- or intermediate-risk neuroblastoma studies (COG-P9641, COG-A3961) prior to determination of MYCN amplification and Shimada histology Endocrine therapy * Not specified Radiotherapy * Prior localized emergency radiotherapy to sites of life-threatening or function-threatening disease allowed Surgery * Not specified Other * No other prior systemic therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

UCSF Comprehensive Cancer Center

San Francisco, California, 94143-0106, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Mary Bridge Children's Hospital and Health Center - Tacoma

Tacoma, Washington, 98405, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Related Publications (1)

• Park JR, Scott JR, Stewart CF, London WB, Naranjo A, Santana VM, Shaw PJ, Cohn SL, Matthay KK. Pilot induction regimen incorporating pharmacokinetically guided topotecan for treatment of newly diagnosed high-risk neuroblastoma: a Children's Oncology Group study. J Clin Oncol. 2011 Nov 20;29(33):4351-7. doi: 10.1200/JCO.2010.34.3293. Epub 2011 Oct 17.

  PMID: 22010014 RESULT

MeSH Terms

Conditions

Neuroblastoma

Interventions

Filgrastim; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; Isotretinoin; Melphalan; Topotecan; Vincristine; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Julie R. Park, MD

  Seattle Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2003
• First Posted: October 7, 2003
• Study Start: March 1, 2004
• Primary Completion: September 1, 2006
• Study Completion: December 1, 2013
• Last Updated: February 13, 2014

Record last verified: 2014-02

Locations

US (5); AU (1)