Phase 3
N=464
Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma
Neuroblastoma
Bottom Line
View on ClinicalTrials.gov: NCT00499616 ↗Enrolled (actual)
464
Serious AEs
3.6%
Results posted
Jun 2017
Primary outcome: Primary: Overall Survival (OS) Rates — 99.4; 93.5; 88.4 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- carboplatin (Drug); cyclophosphamide (Drug); doxorubicin hydrochloride (Drug); etoposide (Drug); topotecan hydrochloride (Drug); Isotretinoin (Drug); Surgery (Procedure); Filgrastim (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Children's Oncology Group
- Primary completion
- Jun 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) Rates |
99.4; 93.5; 88.4 | — |
| PRIMARY Definitive Determination of the Prognostic Ability of 1p and 11q |
87.2; 84.6; 65.4; 99.4; 92.8; 83.7 | — |
| PRIMARY Comparison Between Reduce Intensity of Therapy for Patients With Stage 4 Neuroblastoma and Favorable Biological Features and Patients < 1 Year of Age With Stage 4 Neuroblastoma Treated on COG-A3961 |
66.7 | .3212 |
| PRIMARY Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961 |
100.0 | — |
| PRIMARY Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma |
0.18; 0.11; 0 | — |
| PRIMARY Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment |
50.0; 25.0 | — |
| PRIMARY Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS) |
95.4; 88.4; 78.6; 82.2; 85.1; 69.2 | .0253 sig |
| PRIMARY Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates |
100.0; 95.4; 96.4; 99.1; 93.5; 86.5 | .1022 |
| PRIMARY Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate |
.32; .19; .18; .14; .13; .09 | .0016 sig |
| SECONDARY Second-event-free Survival (E2FS) |
57.14 | — |
| SECONDARY Second-Overall Survival |
85.71 | — |
| SECONDARY Biological Surrogate Markers |
— | — |
| SECONDARY Neurologic Symptoms |
36.57; 35.46; 27.27 | — |
| SECONDARY Association Between Surgical Biopsy Technique With Adequacy of Tissue Acquisition for Biologic Studies, and With Complications Associated With the Biopsy Procedure |
— | — |
| SECONDARY Image Defined Risk Factor (IDRF) |
54.86; 60.28; 56.82 | — |
Summary
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.
Eligibility Criteria
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; 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 1; normal 1p and 11q; clinically symptomatic
- Group 3
- INSS stage 2A/2B; 1; 1p LOH and/or unb11q LOH (or data missing for either)
- INSS stage 3; age 1; normal 1p and 11q
- INSS stage 4S; age 1; 1p LOH and/or unb11q LOH (or data missing for either); clinically symptomatic
- Group 4
- INSS stage 3; age 1; 1p LOH and/or unb11q LOH (or data missing for either)
- INSS stage 4; age 365 to 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 cir
Data sourced from ClinicalTrials.gov (NCT00499616). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.