DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

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


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 deaths

Proportion 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


- 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.


Minimum age: N/A. Maximum age: 30 Years. Gender(s): Both.



- 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


- 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


- 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


- 30 and under at initial diagnosis

Performance status

- Not specified

Life expectancy

- Not specified


- 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


- Creatinine no greater than 1. 5 mg/dL

- Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min


- ECG normal

- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative


- Not specified


- 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


- Prior localized emergency radiotherapy to sites of life-threatening or

function-threatening disease allowed Surgery

- Not specified


- 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

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017