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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00499616
First received: July 10, 2007
Last updated: June 26, 2017
Last verified: June 2015
Results First Received: December 1, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: No masking;   Primary Purpose: Treatment
Condition: Neuroblastoma
Interventions: Drug: carboplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: topotecan hydrochloride
Drug: Isotretinoin
Procedure: Surgery
Drug: Filgrastim

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Group 2 (Chemotherapy, Surgery) 2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
Group 3 (Chemotherapy, Surgery) 4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) 8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo 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.
Non-intermediate Risk Enrolled on Intermediate Risk Trial

The no treatment group assignment patients may have received some treatment on ANBL0531 but they were not evaluable on this study due to being non-intermediate risk and hence did not receive a treatment assignment on ANBL0531.

Surgery: With the exception of patients with INSS 4S disease, patients undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.


Participant Flow:   Overall Study
    Group 2 (Chemotherapy, Surgery)   Group 3 (Chemotherapy, Surgery)   Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)   Non-intermediate Risk Enrolled on Intermediate Risk Trial
STARTED   176   142   89   57 
COMPLETED   161   114   53   0 
NOT COMPLETED   15   28   36   57 
Death                1                5                3                1 
Lack of Efficacy                5                0                19                0 
Lost to Follow-up                0                0                1                0 
Physician Decision                6                16                9                0 
Withdrawal by Subject                1                0                1                0 
Ineligible                1                2                0                15 
Not evaluable                0                0                0                41 
Patient/Parent Refusal                1                5                3                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Group 2 (Chemotherapy, Surgery) 2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
Group 3 (Chemotherapy, Surgery) 4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) 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.
Non-intermediate Risk Enrolled on Intermediate Risk Trial

The no treatment group assignment patients may have received some treatment on ANBL0531 but they were not evaluable on this study due to being non-intermediate risk and hence did not receive a treatment assignment on ANBL0531.

Surgery: With the exception of patients with INSS 4S disease, patients undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.

Total Total of all reporting groups

Baseline Measures
   Group 2 (Chemotherapy, Surgery)   Group 3 (Chemotherapy, Surgery)   Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)   Non-intermediate Risk Enrolled on Intermediate Risk Trial   Total 
Overall Participants Analyzed 
[Units: Participants]
 176   142   89   57   464 
Age 
[Units: Participants]
Count of Participants
         
<=18 years      176 100.0%      142 100.0%      89 100.0%      57 100.0%      464 100.0% 
Between 18 and 65 years      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
>=65 years      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Age 
[Units: Years]
Mean (Standard Deviation)
 1.23  (1.47)   .74  (.89)   .60  (.36)   1.51  (1.83)   0.99  (1.26) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      70  39.8%      72  50.7%      49  55.1%      26  45.6%      217  46.8% 
Male      106  60.2%      70  49.3%      40  44.9%      31  54.4%      247  53.2% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
         
Hispanic or Latino      18  10.2%      26  18.3%      7   7.9%      6  10.5%      57  12.3% 
Not Hispanic or Latino      150  85.2%      109  76.8%      74  83.1%      49  86.0%      382  82.3% 
Unknown or Not Reported      8   4.5%      7   4.9%      8   9.0%      2   3.5%      25   5.4% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native      0   0.0%      0   0.0%      2   2.2%      0   0.0%      2   0.4% 
Asian      5   2.8%      8   5.6%      4   4.5%      2   3.5%      19   4.1% 
Native Hawaiian or Other Pacific Islander      3   1.7%      4   2.8%      0   0.0%      1   1.8%      8   1.7% 
Black or African American      23  13.1%      12   8.5%      8   9.0%      9  15.8%      52  11.2% 
White      133  75.6%      92  64.8%      59  66.3%      40  70.2%      324  69.8% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      12   6.8%      26  18.3%      16  18.0%      5   8.8%      59  12.7% 
Region of Enrollment 
[Units: Participants]
         
New Zealand   2   0   1   0   3 
Canada   16   6   10   5   37 
United States   153   131   78   50   412 
Australia   5   5   0   2   12 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival (OS) Rates   [ Time Frame: 3 years ]

2.  Primary:   Definitive Determination of the Prognostic Ability of 1p and 11q   [ Time Frame: At baseline ]

3.  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   [ Time Frame: Up to 3 years ]

4.  Primary:   Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961   [ Time Frame: Up to 3 years ]

5.  Primary:   Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma   [ Time Frame: Up to 3 years ]

6.  Primary:   Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment   [ Time Frame: From baseline to up to 10 years ]

7.  Primary:   Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS)   [ Time Frame: Up to 10 years ]

8.  Primary:   Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates   [ Time Frame: Up to 10 years ]

9.  Primary:   Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate   [ Time Frame: Up to 10 years ]

10.  Secondary:   Biological Surrogate Markers   [ Time Frame: At baseline and surgery ]

11.  Secondary:   Association Between Surgical Biopsy Technique With Adequacy of Tissue Acquisition for Biologic Studies, and With Complications Associated With the Biopsy Procedure   [ Time Frame: During and after surgery ]

12.  Secondary:   Second-event-free Survival (E2FS) of Intermediate Risk Patients   [ Time Frame: From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse, progressive disease, secondary malignancy, or death ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

13.  Secondary:   Overall Survival Time   [ Time Frame: From the time of the first progressive, non-metastatic event ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

14.  Secondary:   Proportion of Patients With Neurologic Symptoms Overall and Type of Symptom   [ Time Frame: On treatment and post-treatment ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

15.  Secondary:   Prognostic Ability of the INRG Image-defined Risk Factor (IDRF) System   [ Time Frame: At baseline, during and after completion of study treatment ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
phone: 626-447-0064
e-mail: resultsreportingcoordinator@childrensoncologygroup.org



Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00499616     History of Changes
Other Study ID Numbers: ANBL0531
COG-ANBL0531 ( Other Identifier: Children's Oncology Group )
NCI-2009-00400 ( Other Identifier: CTRP (Clinical Trial Reporting Program) )
Study First Received: July 10, 2007
Results First Received: December 1, 2015
Last Updated: June 26, 2017