Induction Chemotherapy Using Cyclophosphamide and Topotecan in Treating Patients Who Are Undergoing Autologous Peripheral Stem Cell Transplantation for Newly Diagnosed or Progressive Neuroblastoma
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: Neuroblastoma
Intervention: filgrastim (Biological); cisplatin (Drug); cyclophosphamide (Drug); doxorubicin hydrochloride (Drug); etoposide (Drug); isotretinoin (Drug); melphalan (Drug); topotecan hydrochloride (Drug); vincristine sulfate (Drug); conventional surgery (Procedure); peripheral blood stem cell transplantation (Procedure); radiation therapy (Radiation)
Phase: Phase 1
Status: Completed
Sponsored by: Children's Oncology Group Official(s) and/or principal investigator(s): Julie R. Park, MD, Study Chair, Affiliation: Seattle Children's Hospital
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.
Clinical Details
Official title: A Pilot Induction Regimen Incorporating Topotecan for Treatment of Newly Diagnosed High Risk Neuroblastoma
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Proportion of patients who are classified as a "success"
Secondary outcome: Number of toxic deathsProportion of patients with dose limiting toxicities during induction cycle 1 and 2 Tumor contamination of PBSCs Inability to adequately mobilize PBSCs Assessment of response
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
Minimum age: N/A.
Maximum age: 30 Years.
Gender(s): Both.
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
Locations and Contacts
UCSF Comprehensive Cancer Center, San Francisco, California 94143-0106, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
Westmead Hospital, Westmead, New South Wales 2145, Australia
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Mary Bridge Children's Hospital and Health Center - Tacoma, Tacoma, Washington 98405, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: March 2004
Last updated: February 12, 2014
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