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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070200

Purpose

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.

Condition	Intervention	Phase
Neuroblastoma	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	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Pilot Induction Regimen Incorporating Topotecan for Treatment of Newly Diagnosed High Risk Neuroblastoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

March 2004

Detailed Description:

OBJECTIVES:

Primary

Determine the toxicity and feasibility of adding cyclophosphamide and topotecan to induction therapy in patients with newly diagnosed or progressive high-risk neuroblastoma undergoing autologous peripheral blood stem cell (PBSC) transplantation.
Determine the feasibility of PBSC mobilization and in vivo PBSC tumor purging in these patients after treatment with this regimen.

Secondary

Determine tumor response rate in patients treated with this regimen.
Determine the pharmacokinetics of this regimen in these patients.
Determine whether topotecan affects cyclophosphamide pharmacokinetics in these patients.
Correlate host DNA with toxicity and cyclophosphamide and topotecan pharmacokinetics in patients treated with this regimen.
Determine toxicity in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study. Patients are stratified according to diagnosis (newly diagnosed vs initially stage 1, 2, or 4S that progressed to stage 4 without interval chemotherapy).

Induction therapy: Patients receive 6 courses of induction therapy.
- Courses 1 and 2: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 6 and continuing until blood counts recover.
- Course 3: Patients receive etoposide IV over 2 hours on days 1-3, cisplatin IV over 1 hour on days 1-4, and G-CSF SC or IV beginning on day 5 and continuing until blood counts recover.
- Course 4: Patients receive cyclophosphamide IV over 6 hours on day 1 and doxorubicin IV and vincristine IV continuously over 24 hours on days 1-3. Patients also receive G-CSF SC or IV beginning on day 4 and continuing until blood counts recover.
- Course 5: Patients receive etoposide, cisplatin, and G-CSF as in course 3.
- Course 6: Patients receive cyclophosphamide, doxorubicin, vincristine, and G-CSF as in course 4.

Treatment repeats every 21 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Consolidation therapy: Within 4-6 weeks after completing induction therapy, patients receive melphalan IV on days -7 to -5 and etoposide IV and carboplatin IV continuously over 24 hours on days -7 to -4.
Stem cell transplantation: Peripheral blood stem cells are collected after course 2 of induction therapy and infused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover.
Surgery: After course 5 of induction therapy, patients undergo surgery.
Radiotherapy: Beginning 28-42 days after transplantation, patients receive 12 fractions of local radiotherapy to all areas of residual soft tissue disease and the primary tumor site, even if completely resected.
Maintenance therapy: Beginning 66 days after transplantation, patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 10-29 patients will be accrued for this study within 2 years.

Eligibility

Ages Eligible for Study:	up to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070200

Locations

United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0106
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Mary Bridge Children's Hospital and Health Center - Tacoma
Tacoma, Washington, United States, 98405
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia, 2145

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Julie R. Park, MD

Seattle Children's Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000330140, COG-ANBL02P1
Study First Received:	October 3, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00070200 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma

localized resectable neuroblastoma
regional neuroblastoma
disseminated neuroblastoma

Additional relevant MeSH terms:

Melphalan
Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neuroblastoma
Cisplatin
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Isotretinoin
Dermatologic Agents

Alkylating Agents
Etoposide
Neoplasms by Histologic Type
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 27, 2009