Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma

Not Recruiting

Trial ID: NCT00499616

Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Isotretinoin may help neuroblastoma cells become more like normal cells, and grow and spread more slowly. Giving combination chemotherapy before surgery may make the tumor smaller and make it more likely that the tumor can be surgically removed. It is not yet known what is the minimal amount of chemotherapy needed to achieve sufficient tumor shrinkage to control intermediate risk neuroblastoma and prevent tumor recurrence or metastases. PURPOSE: This phase III trial is designed to reduce therapy for patients with favorable biology intermediate risk neuroblastoma by decreasing the number of chemotherapy cycles administered and by allowing for up to 50% residual tumor volume for patients with localized disease.

Official Title

Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma

Stanford Investigator(s)

Eligibility

DISEASE CHARACTERISTICS:

* Histologically confirmed neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/maturing subtype

* Newly diagnosed disease
* Intermediate-risk disease
* Needle biopsies or involved bone marrow are not sufficient for INPC histologic classification
* Meets 1 of the following criteria:

* Group 2

* International Neuroblastoma Staging System (INSS) stage 2A/2B; \< 50% resected or biopsy only; ≤ 12 years of age; MYCN-not amplified (NA); any histology and ploidy; normal 1p and 11q
* INSS stage 3; age \< 365 days; MYCN-NA; favorable histology (FH); hyperdiploid (DI) \> 1; normal 1p and 11q
* INSS stage 3; 365 days to 12 years of age; MYCN-NA; FH; normal 1p and 11q
* INSS stage 4S; age \< 365 days; MYCN-NA; FH; DI \>1; normal 1p and 11q; clinically symptomatic
* Group 3

* INSS stage 2A/2B; \< 50% resected or biopsy only; ≤ 12 years of age; MYCN-NA; any histology and ploidy; 1p loss of heterozygosity (LOH) and/or unb11q LOH (or data missing for either)
* INSS stage 3; age \< 365 days; MYCN-NA; FH; DI \> 1; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 3; age \< 365 days; MYCN-NA; DI = 1 and/or unfavorable histology (UH); normal 1p and 11q
* INSS stage 3; 365 days to 12 years of age; MYCN-NA; FH; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 4; age \< 365 days; MYCN-NA; FH; DI \> 1; normal 1p and 11q
* INSS stage 4S; age \< 365 days; MYCN-NA; either UH and any ploidy or FH and DI = 1; normal 1p and 11q
* INSS stage 4S; age \< 365 days; MYCN-NA; FH; DI \> 1; 1p LOH and/or unb11q LOH (or data missing for either); clinically symptomatic
* Group 4

* INSS stage 3; age \< 365 days; MYCN-NA; DI = 1 and/or UH; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 3; age 365 to \< 547 days; MYCN-NA; UH; any ploidy; any 1p and 11q
* INSS stage 4, age \< 365 days; MYCN-NA; DI = 1 and/or UH; any 1p and 11q
* INSS stage 4; age \< 365 days; MYCN-NA; FH; DI \> 1; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 4; age 365 to \< 547 days; MYCN-NA; FH; DI \> 1; any 1p and 11q
* INSS stage 4S; age \< 365 days; MYCN-NA; UH and any ploidy or FH and DI = 1; 1p LOH and/or unb11q LOH (or data missing for either)
* INSS stage 4S; age \< 365 days; unknown or incomplete biologic features

8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim.

Patients \< 12 months of age with stg 3, 4, or 4S disease who achieve a very good PR (VGPR) to chemo (with the exception of resolution of skin or liver metastases in stage 4S patients) proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

* Must already be enrolled on protocol COG-ANBL00B1

* Simultaneous enrollment on COG-ANBL00B1 and this study allowed for clinical situations in which emergent treatment may be indicated including, but not limited to, the following criteria:

* Epidural or intraspinal tumors with existing or impending neurologic impairment
* Periorbital or calvarial-based lesions with existing or impending cranial nerve impairment
* Anatomic or mechanical compromise of critical organ function by tumor (e.g., abdominal compartment syndrome, urinary obstruction)
* Asymptomatic but, in the opinion of the treating physician, it is in the patient's best interest to begin chemotherapy immediately due to impending risk of neurologic impairment or organ dysfunction
* If patient receives study chemotherapy prior to undergoing diagnostic biopsy, the biopsy must be performed within 96 hours of beginning study therapy

* The only exception to this requirement is for patients with stage 4S disease who are considered too ill to undergo a diagnostic procedure will be waived the requirement for diagnostic tissue submission but will still need to be enrolled on COG-ANBL00B1

* For patients with stage 4S disease who are very ill and in whom an open biopsy to obtain tissue for diagnosis and biologic studies is considered medically contraindicated, every effort should be made to obtain some tumor tissue by either fine-needle aspiration of a metastatic site of disease and/or sampling of involved bone marrow, so that this tumor sample can be submitted for MYCN determination
* Patients who require emergent therapy, either prior to the diagnostic biopsy or before biology features are available, can be enrolled simultaneously on COG-ANBL00B1 and COG-ANBL0531 to receive emergent protocol therapy

* In emergent circumstances, COG-ANBL0531 protocol therapy may be initiated prior to enrollment on study as long as the patient has neuroblastoma by clinical diagnosis, all other COG-ANBL0531 eligibility criteria are met, and the COG-ANBL0531 Initial Therapy consent has been signed prior to starting protocol therapy; in this circumstance ANBL0531 enrollment must occur within 4 working days of starting protocol therapy
* Clinical situations in which emergent enrollment and treatment may be indicated include, but are not limited to, the following circumstances:

* Epidural or intraspinal tumors with existing or impending neurologic impairment
* Periorbital or calvarial-based lesions with existing or impending cranial nerve impairment
* Anatomic or mechanical compromise of critical organ function by tumor (e.g., abdominal compartment syndrome, urinary obstruction)
* Evolving hepatomegaly in infants less than 2 months of age

PATIENT CHARACTERISTICS:

* See Disease Characteristics

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No other prior chemotherapy or radiotherapy with the exception of dexamethasone
* No participation in another COG study with tumor therapeutic intent

Intervention(s):

drug: carboplatin

drug: cyclophosphamide

drug: doxorubicin hydrochloride

drug: etoposide

drug: topotecan hydrochloride

drug: Isotretinoin

procedure: Surgery

drug: Filgrastim

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Peds Hem/Onc CRAs
650-723-5535

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