Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Surgery in Treating Children With Neuroblastoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	Under 21	NCI	COG-P9641 POG-P9641, CCG-P9641, NCT00003119, P9641

Objectives

1. To determine if asymptomatic patients with low-risk neuroblastoma treated with surgery alone will have a 3-year survival rate of 95%.
2. Estimate the response and 3-year event-free survival rates of symptomatic patients treated with chemotherapy.
3. Estimate the event-free survival and overall survival rates in patients who relapse or progress after initial treatment with surgery alone.
4. Determine the acute and chronic toxic effects associated with treating low-risk neuroblastoma with surgery alone or surgery and chemotherapy.

Entry Criteria

Disease Characteristics:

• Histologically proven low-risk neuroblastoma (excluding ganglioneuroma)
  • International Neuroblastoma Staging System (INSS) stage 1 in all patients
  • INSS stage 2A or 2B in patients less than 365 days of age
  • INSS stage 2A or 2B tumor with nonamplified MYCN with any Shimada histology in patients ages 1 to 20 years
  • INSS stage 2A or 2B tumor with amplified MYCN with Shimada favorable histology in patients ages 1 to 20 years
  • INSS stage 4S tumors with nonamplified MYCN, Shimada favorable histology, and a DNA index not equal to 1 in patients less than 365 days of age



• Immediate chemotherapy allowed prior to biopsy for patients with intradural extension and/or emergent paresis if biopsy performed within 96 hours
  • Must have no abnormal organ function unless due to neuroblastoma



• Concurrent registration on companion biology study (protocol COG-ANBL00B1) or its successor

Prior/Concurrent Therapy:

Biologic therapy:

• No prior immunotherapy

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• No prior hormonal therapy

Radiotherapy:

• No prior radiotherapy

Surgery:

• Prior surgery allowed

Other:

• No other prior therapy

Patient Characteristics:

Age:

• Under 21

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 1.5 times normal
• SGOT or SGPT less than 2.5 times normal

Renal:

• Creatinine less than 1.5 times normal

Cardiovascular:

• Shortening fraction greater than 27% by echocardiogram

  OR

• Ejection fraction greater than 47% by radionuclide angiogram

Expected Enrollment

A total of 820 patients will be accrued for this study within 4 years.

Outline

This is a multicenter study. Patients are stratified according to disease stage, MYCN status, age, and histology.

Patients undergo primary tumor resection and biopsy of regional nodes. Patients with at least 50% of the tumor resected are followed monthly for 3 months, every 3 months for 9 months, every 6 months for one year, and then annually thereafter.

Regimen I

• Patients with clinically symptomatic (e.g., respiratory distress, spinal cord compromise with or without neurologic deficit, inferior vena cava compression with renal or bowel ischemia, intractable vomiting due to gastrointestinal obstruction, genitourinary obstruction, or coagulopathy) low-risk neuroblastoma or who have less than 50% of the primary tumor resected receive 4 different courses of chemotherapy.



• Course 1: Patients receive carboplatin IV over 1 hour followed by etoposide IV over 2 hours on day 0 and etoposide only on days 1 and 2.



• Course 2: Patients receive carboplatin IV over 1 hour, cyclophosphamide IV over 1 hour, and doxorubicin IV over 15-60 minutes on day 1.



• Course 3: Patients receive cyclophosphamide IV over 1 hour followed by etoposide IV over 2 hours on day 0 and etoposide only on days 1 and 2.



• Course 4: Patients receive carboplatin IV over 1 hour and etoposide IV over 2 hours followed by doxorubicin IV over 15-60 minutes on day 0 and etoposide only on days 1 and 2.

Regimen II

• Patients who progress to or recur with unfavorable biology intermediate-risk disease receive an additional 4 courses of chemotherapy.



• Course 5: Patients receive treatment as in course 3 above.



• Course 6: Patients receive treatment as in course 2 above.



• Course 7: Patients receive treatment as in course 1 above.



• Course 8: Patients receive cyclophosphamide IV over 1 hour followed by doxorubicin IV over 15-60 minutes on day 1.

All infants under 60 days of age receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 to 36 hours after chemotherapy and continuing until blood counts recover.

Courses in both regimens repeat every 3 weeks in the absence of unacceptable toxicity.

Patients at risk for symptomatic spinal cord compression may also receive chemotherapy. Patients experiencing progressive or recurrent disease after observation undergo repeat surgery and/or chemotherapy as above. Patients with clinically symptomatic disease may also undergo radiotherapy if response to chemotherapy is not rapid.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Attiyeh EF, Mosse YP, Diskin S, et al.: Identification of genomic DNA signatures predicting relapse in low- and intermediate- risk neuroblastoma using a case control design and high-density SNP genotyping: a Children's Oncology Group (COG) study. [Abstract] J Clin Oncol 25 (Suppl 18): A-9500, 526s, 2007.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Douglas Strother, MD, Protocol chair		Ph: 403-955-7272

Registry Information
Official Title		Primary Surgical Therapy for Biologically Defined Low-Risk Neuroblastoma: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study
Trial Start Date		1998-03-01
Registered in ClinicalTrials.gov		NCT00003119
Date Submitted to PDQ		1997-10-15
Information Last Verified		2004-06-09
NCI Grant/Contract Number		U10-CA30969

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