Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Followed by Surgery and/or Radiation Therapy in Treating Young Patients With Advanced Neuroblastoma

NCT ID: NCT00002740

Last Updated: 2014-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-05-31

Study Completion Date

2005-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation followed by surgery and/or radiation therapy in treating young patients who have newly diagnosed advanced neuroblastoma.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

OBJECTIVES: I. Estimate the maximum tolerated dose of carboplatin that can be given in combination with cyclophosphamide (CTX) and etoposide following high dose CTX, doxorubicin, and vincristine in patients with newly diagnosed stage IV neuroblastoma. II. Determine the hematologic and nonhematologic toxic effects of this regimen in this patient population. III. Determine the change in neuroblastoma tumor cell content in peripheral blood stem cells (PBSC) collected following chemotherapy. IV. Assess the feasibility of repetitive collection, storage, and infusion of PBSC with multicycle high-dose chemotherapy in pediatric patients. V. Assess hematopoietic recovery following PBSC infusion as well as the CD34 content and CFU-GM yield of the PBSC products. VI. Assess the response rate and disease-free survival in the context of a phase I pilot study. VII. Determine the feasibility of administering twice-daily radiotherapy fractions to post-chemotherapy residual tumor volumes in neuroblastoma patients.

OUTLINE: This is a dose escalation study of carboplatin. Patients receive induction chemotherapy consisting of vincristine IV over 24 hours, cyclophosphamide IV over 4 hours, and doxorubicin IV over 24 hours on days 0, 1, 21, and 22. Patients receive filgrastim (G-CSF) subcutaneously (SQ) or IV beginning on days 3 and 24 and continuing until blood counts recover. Patients undergo peripheral blood stem cell (PBSC) collection after course 2 of induction chemotherapy. Patients receive G-CSF SQ or IV for 2 days prior to and during collection. PBSC are collected daily for 1-3 days. Patients may undergo autologous bone marrow collection after course 1 of consolidation therapy (after PBSC collection). Following mobilization, patients receive consolidation chemotherapy consisting of etoposide IV over 4 hours on days 0, 1, and 2 and carboplatin IV over 1 hour and cyclophosphamide IV over 4 hours on days 0 and 1. Patients receive G-CSF SQ or IV beginning on day 3 (within 4 hours of PBSC infusion) and continuing until blood counts recover. Patients receive PBSC reinfusion at 48-72 hours following completion of each chemotherapy course. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Upon recovery from consolidation chemotherapy, patients with no disease progression undergo tumor resection with or without radiotherapy. Patients undergoing radiotherapy receive therapy twice daily over 7 days. Patients with no disease progression, less than 2% detectable bone marrow disease, and adequate bone marrow cellularity may undergo additional therapy consisting of autologous bone marrow transplantation per appropriate transplant protocol. Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose limiting toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within approximately 2 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Neuroblastoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Primary Study Purpose

TREATMENT

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment - Carboplatin Chemotherapy

See detailed description.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

mesna

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

low-LET cobalt-60 gamma ray therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

filgrastim

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide

Intervention Type DRUG

mesna

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

low-LET cobalt-60 gamma ray therapy

Intervention Type RADIATION

low-LET photon therapy

Intervention Type RADIATION

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

G-CSF (Granulocyte colony stimulating factor Neupogen NSC# 614629 CBDCA Cis-diamine [1,1-cyclobutane-dicarboxylato] platinum) NSC# 241240 Cytoxan CTX NSC# 26271 Adriamycin NSC #123127 VP-16 NSC# 141540 Sodium 2-mercaptoethane sulfonate NSC# 113891 Oncovin VCR Leucocristine NSC# 67474

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

DISEASE CHARACTERISTICS: Newly diagnosed stage IV neuroblastoma by one of the following: Histologic verification Demonstration of tumor cell clumps in bone marrow with elevated urinary catecholamine metabolites Initial presentation with low-stage disease allowed if followed by progression to stage IV disease

PATIENT CHARACTERISTICS: Age: 1 to 21 Performance status: Not specified Hematopoietic: (unless bone marrow involvement by tumor) Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 3.0 mg/dL Renal: Creatinine less than 1.5 mg/dL Creatinine clearance or radionuclide GFR greater than 60 mL/min Cardiovascular: EKG normal Ejection fraction at least 55% by radionuclide MUGA OR Fractional shortening at least 28% by echocardiogram Other: No other significant organ dysfunction that precludes study treatment Body weight at least 10 kg Not pregnant or nursing Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: No prior systemic chemotherapy No prior radiotherapy except as emergency treatment
Minimum Eligible Age

1 Year

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Susan G. Kreissman, MD

Role: STUDY_CHAIR

Duke Cancer Institute

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Columbus

Columbus, Ohio, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Bensimhon P, Villablanca JG, Sender LS, Matthay KK, Park JR, Seeger R, London WB, Yap JS, Kreissman SG. Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: a report from the Childrens Oncology Group. Pediatr Blood Cancer. 2010 Apr;54(4):596-602. doi: 10.1002/pbc.22344.

Reference Type RESULT
PMID: 20049927 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CCG-3951

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000064656

Identifier Type: OTHER

Identifier Source: secondary_id

3951

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.