Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	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 with or without isotretinoin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which treatment regimen is more effective in treating young patients with neuroblastoma.

PURPOSE: This phase III trial is comparing different regimens of combination chemotherapy and surgery with or without isotretinoin to see how well they work in treating young patients with neuroblastoma.

Condition	Intervention	Phase
Neuroblastoma	Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: isotretinoin Drug: topotecan hydrochloride Procedure: conventional surgery	Phase III

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Carboplatin Etoposide Isotretinoin Topotecan hydrochloride Topotecan Etoposide phosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	395
Study Start Date:	October 2007
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Experimental Patients receive courses 1-2 of initial chemotherapy. Patients with a partial response (PR) proceed to observation. Patients without a PR continue to receive 2-6 additional courses of chemotherapy (beginning with course 3) until PR is achieved. Patients who do not achieve a PR after additional chemotherapy proceed to retrieval chemotherapy comprising cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may then receive isotretinoin therapy. Some patients may also undergo surgery.	Drug: carboplatin Given IV Drug: cyclophosphamide Given IV Drug: etoposide Given IV Drug: isotretinoin Oral, twice daily Drug: topotecan hydrochloride Given IV Procedure: conventional surgery With the exception of patients with INSS 4S disease, patients will undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.
Group 2: Experimental Patients receive courses 1-4 of initial chemotherapy. Patients with a PR proceed to observation. Patients without a PR continue to receive 2-4 additional courses of chemotherapy (beginning with course 3) until PR is achieved. Patients who do not achieve a PR after additional chemotherapy proceed to retrieval chemotherapy. Patients receive Retrieval chemotherapy as in group 1. Some patients may then receive isotretinoin therapy. Some patients may also undergo surgery.	Drug: carboplatin Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: isotretinoin Oral, twice daily Drug: topotecan hydrochloride Given IV Procedure: conventional surgery With the exception of patients with INSS 4S disease, patients will undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.
Group 3: Experimental Patients receive courses 1-8 of initial chemotherapy. Patients under 12 months of age with stage 4 disease who achieve a very good (VG) PR proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease who achieve a VGPR proceed to isotretinoin therapy. Patients who do not achieve a VGPR proceed to retrieval chemotherapy. Patients receive Retrieval chemotherapy as in group 1. Some patients may then receive isotretinoin therapy. Some patients may also undergo surgery.	Drug: carboplatin Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: isotretinoin Oral, twice daily Drug: topotecan hydrochloride Given IV Procedure: conventional surgery With the exception of patients with INSS 4S disease, patients will undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.

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Eligibility

Ages Eligible for Study:	up to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed neuroblastoma or ganglioneuroblastoma
- Newly diagnosed disease
- Intermediate-risk disease
Meets 1 of the following criteria:
- Group 1
  - International Neuroblastoma Staging System (INSS) stage 2A/2B < 50% resected or biopsy only, age 0 to 12 years, MYCN-not amplified (NA), any histology, any ploidy, normal 1p and 11q
  - INSS stage 3, age < 365 days, MYCN-NA, favorable histology (FH), hyperdyploid (DI) > 1, normal 1p and 11q
  - INSS stage 3, age ≥ 365 days to 12 years, MYCN-NA, FH, normal 1p and 11q
  - INSS stage 4S, age < 365 days, MYCN-NA, FH, DI > 1, normal 1p and 11q, but clinically symptomatic
- Group 2
  - INSS stage 2A/2B < 50% resected or biopsy only, age 0 to ≤ 12 years, MYCN-NA, any histology and ploidy, 1p loss of heterozygosity (LOH) and/or unb11q LOH (or data missing for either)
  - INSS stage 3, < 365 days old, MYCN-NA, FH, DI > 1, 1p LOH and/or unb11q LOH (or data missing for either)
  - inss Stage 3, < 365 days old, MYCN-na, either DI = 1 and/or unfavorable histology (UH), normal 1p and 11q
  - INSS stage 3, ≥ 365 days to 12 years old, MYCN-NA, FH, 1p LOH and/or unb11q LOH (or data missing for either)
  - INSS stage 4, < 365 days old, MYCN-NA, FH, DI > 1, normal 1p and 11q
  - INSS stage 4S, < 365 days old, MYCN-NA, either UH and any ploidy, or FH and DI = 1, normal 1p and 11q
  - INSS stage 4S, < 365 days old, MYCN-NA, FH, DI > 1, 1p LOH and/or unb11q LOH (or data missing for either) and clinically symptomatic
  - INSS stage 4S, < 365 days old, unknown MYCN, histology, and/or ploidy
- Group 3
  - INSS stage 3, < 365 days old, MYCN-NA, either DI = 1 and/or UH, 1p LOH and/or unb11q LOH (or data missing for either)
  - INSS stage 3, 365 to < 547 days old, MYCN-NA, UH, any ploidy, any 1p and 11q
  - INSS stage 4, < 365 days old, MYCN-NA, either 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, 365 to < 547 days old, MYCN-NA, FH, DI > 1, any 1p and 11q
  - INSS stage 4S, < 365 days old, MYCN-NA, either UH and any ploidy or FH and DI = 1 and 1p LOH and/or unb11q LOH (or data missing for either)
Must be enrolled on protocol COG-ANBL00B1

PATIENT CHARACTERISTICS:

See Disease Characteristics

PRIOR CONCURRENT THERAPY:

No prior chemotherapy with the exception of the following:
- Patients with intradural tumor extension and emergent paresis can be given chemotherapy according to COG-ANBL0531 prior to biopsy provided the biopsy is subsequently performed within 96 hours
- Patients without symptoms may be enrolled and treated immediately with chemotherapy at the discretion of the investigator if it is considered to be in the best interest of the patient (e.g., a patient with intradural tumor extension who is at risk of developing neurologic deficits)
- Prior dexamethasone allowed at the discretion of the investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499616

Show 153 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Clare Twist, MD	Lucile Packard Children's Hospital at Stanford University Medical Center
Investigator:	Mary Lou Schmidt, MD	University of Illinois

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000554708, COG-ANBL0531
Study First Received:	July 10, 2007
Last Updated:	October 21, 2008
ClinicalTrials.gov Identifier:	NCT00499616
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma
localized resectable neuroblastoma

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Cyclophosphamide
Carboplatin
Etoposide phosphate
Neuroblastoma
Doxorubicin
Neuroectodermal Tumors

Neoplasms, Germ Cell and Embryonal
Isotretinoin
Neuroepithelioma
Topotecan
Etoposide
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antirheumatic Agents
Dermatologic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009