Know Cancer

or
forgot password

A Pilot Induction Regimen Incorporating Topotecan for Treatment of Newly Diagnosed High Risk Neuroblastoma


Phase 1
N/A
30 Years
Not Enrolling
Both
Neuroblastoma

Thank you

Trial Information

A Pilot Induction Regimen Incorporating Topotecan for Treatment of Newly Diagnosed High Risk Neuroblastoma


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Julie R. Park, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Seattle Children's Hospital

Authority:

United States: Federal Government

Study ID:

CDR0000330140

NCT ID:

NCT00070200

Start Date:

March 2004

Completion Date:

Related Keywords:

  • Neuroblastoma
  • recurrent neuroblastoma
  • stage 4S neuroblastoma
  • localized unresectable neuroblastoma
  • localized resectable neuroblastoma
  • regional neuroblastoma
  • disseminated neuroblastoma
  • Neuroblastoma

Name

Location

Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
St. Jude Children's Research HospitalMemphis, Tennessee  38105-2794
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Mary Bridge Children's Hospital and Health Center - TacomaTacoma, Washington  98405