Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma
- Conditions
- Neuroblastoma
- Interventions
- Registration Number
- NCT00499616
- Lead Sponsor
- Children's Oncology Group
- Brief 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.
- Detailed Description
OBJECTIVES:
Primary
* Reduce therapy for patients with intermediate-risk neuroblastoma while maintaining a 3-year overall survival (OS) rate of ≥ 95% by using a response-based duration of therapy algorithm.
* Maintain an overall 3-year OS rate of ≥ 90% for patients within each group.
* Utilize loss of heterozygosity, prospectively, at 1p36 and 11q23 to refine risk-stratification and treatment assignment, allowing patients whose tumors lack these chromosomal abnormalities to receive a reduction in therapy, and compare the outcome with patients treated on COG-A3961.
* Reduce intensity of therapy for patients 365 to \< 547 days (12-18 months) of age with stage 4 neuroblastoma and favorable biological features and maintain a 3-year event-free survival (EFS) rate consistent with that for patients \< 1 year of age with stage 4 neuroblastoma treated on COG-A3961.
* Reduce intensity of therapy for patients 365 to \< 547 days (12-18 months) of age with stage 3 MYCN-nonamplified but unfavorable histology neuroblastoma and maintain a 3-year EFS rate consistent with that for patients \< 1 year of age with stage 3, MYCN-nonamplified, unfavorable histology neuroblastoma treated on COG-A3961.
* Reduce surgical morbidity for patients with stage 4S neuroblastoma by allowing for biopsy only, rather than complete surgical resection, of the primary tumor.
* Systematically study the outcome of patients with stage 4S neuroblastoma who are unable to undergo biopsy for biology-based risk assignment.
* Determine if the extent of surgical resection correlates with the maintenance of local control, EFS and/or OS rates, and surgical complication rate.
Secondary
* Determine the results of a standard retrieval approach for patients with residual disease after 8 courses of initial therapy.
* Determine the results of a standard retrieval approach for patients with progressive, nonmetastatic disease.
* Identify additional biological surrogate markers for disease relapse and/or metastatic progression.
* Describe the neurologic outcome of patients with paraspinal neuroblastoma primary tumors.
* Correlate surgical biopsy technique with adequacy of tissue acquisition for biologic studies and with complications associated with the biopsy procedure.
* Prospectively validate the prognostic ability of the International Neuroblastoma Risk Group image-defined risk factor system, and compare the institutional assessment of image-defined risk factors with that of central review.
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 3 treatment groups by risk-stratification based on age, stage (INSS stage 2, 3, 4, or 4S), MYCN status (amplified vs not amplified), histopathologic classification, tumor DNA index, and allelic status at chromosome bands 11q23 and 1p36.
* Initial chemotherapy: Courses of initial chemotherapy are administered every 21 days according to group assignment as outlined below:
* Course 1: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
* Course 2: Patients receive carboplatin IV over 1 hour, cyclophosphamide IV over 1 hour, and doxorubicin hydrochloride IV over 15 minutes on day 1.
* Course 3: Patients receive cyclophosphamide IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
* Course 4: Patients receive carboplatin IV over 1 hour and doxorubicin hydrochloride IV over 15 minutes on day 1 and etoposide IV over 1 hour on days 1-3.
* Course 5: Patients receive cyclophosphamide IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
* Course 6: Patients receive carboplatin IV over 1 hour, cyclophosphamide IV over 1 hour, and doxorubicin hydrochloride IV over 15 minutes on day 1.
* Course 7: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3.
* Course 8: Patients receive cyclophosphamide IV over 1 hour and doxorubicin hydrochloride IV over 15 minutes on day 1.
* Group 2: Patients receive 2 courses of initial chemotherapy. Patients with a partial response (PR) (50-90% reduction in volume) to chemotherapy proceed to observation. Patients without a PR receive 2-6 additional courses of chemotherapy (beginning with course 3). Patients who do not achieve a PR after additional chemotherapy proceed to retrieval chemotherapy.
* Group 3: Patients receive 4 courses of initial chemotherapy. Patients with a PR after chemotherapy proceed to observation. Patients without a PR receive 2-4 additional courses of chemotherapy (beginning with course 5). Patients who do not achieve a PR after additional chemotherapy proceed to retrieval chemotherapy.
* Group 4: Patients receive 8 courses of initial chemotherapy. Patients under 12 months of age with stage 3, 4, or 4S disease who achieve a very good PR (VGPR) (\> 90% reduction in the volume of the primary tumor and resolution of metastatic disease, with the exception of liver and skin metastases) to chemotherapy proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease \[age 365 to \< 547 days at diagnosis, INSS stage 3, MYCN-NA, unfavorable histology, any ploidy and patients age 365 to \< 547 days at diagnosis, INSS stage 4, MYCN-NA, favorable histology, DI \> 1\] who achieve a VGPR proceed to isotretinoin therapy. Patients who do not achieve a VGPR after 8 courses of initial chemotherapy +/- surgery will proceed to retrieval chemotherapy with cyclophosphamide/topotecan for 2-6 courses until a VGPR can be achieved with a combination of chemotherapy and surgery.
* Retrieval chemotherapy\*: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 6 courses.
* Groups 2 and 3: Patients with a PR after 2-6 courses of retrieval chemotherapy proceed to observation. Patients without a PR after 2-6 courses of retrieval chemotherapy are removed from protocol therapy.
* Group 4: Patients under 12 months of age with stage 4 disease with a VGPR after retrieval chemotherapy proceed to observation. Patients 12-18 months of age with stage 3 or 4 disease who achieve a VGPR after retrieval chemotherapy proceed to isotretinoin therapy. Patients who do not achieve a VGPR after retrieval chemotherapy are removed from protocol therapy.
Group 4 patients who develop progressive, non-metastatic disease within 3 years of study enrollment will also receive retrieval chemotherapy with cyclophosphamide and topotecan.
NOTE: \*Patients who have previously received cyclophosphamide and topotecan to achieve first PR/VGPR are not eligible for this Retrieval Therapy.
* 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. Reassessment for definitive surgery (for patients who undergo biopsy only or partial resection at diagnosis) is made at the completion of scheduled chemotherapy (after course 2 for group 2, after course 4 for group 3, and after course 8 for group 4).
* Isotretinoin therapy: Beginning 3-4 weeks after completion of chemotherapy or 2 weeks post-operatively (for patients who undergo surgical resection), patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically for up to 10 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 464
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 4 (chemotherapy, surgery, antineoplastic therapy) carboplatin 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. Group 2 (chemotherapy, surgery) topotecan hydrochloride 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) topotecan hydrochloride 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 3 (chemotherapy, surgery) 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 2 (chemotherapy, surgery) 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 4 (chemotherapy, surgery, antineoplastic therapy) doxorubicin hydrochloride 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. Group 4 (chemotherapy, surgery, antineoplastic therapy) topotecan hydrochloride 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. Group 4 (chemotherapy, surgery, antineoplastic therapy) Surgery 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 Surgery 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. Group 2 (chemotherapy, surgery) carboplatin 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 2 (chemotherapy, surgery) cyclophosphamide 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 2 (chemotherapy, surgery) doxorubicin hydrochloride 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 2 (chemotherapy, surgery) etoposide 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 2 (chemotherapy, surgery) Filgrastim 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) carboplatin 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 3 (chemotherapy, surgery) cyclophosphamide 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 3 (chemotherapy, surgery) doxorubicin hydrochloride 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 3 (chemotherapy, surgery) etoposide 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 3 (chemotherapy, surgery) Filgrastim 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) cyclophosphamide 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. Group 4 (chemotherapy, surgery, antineoplastic therapy) etoposide 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. Group 4 (chemotherapy, surgery, antineoplastic therapy) Isotretinoin 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. Group 4 (chemotherapy, surgery, antineoplastic therapy) Filgrastim 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Rates 3 years OS time is calculated from date of enrollment until death, or until last contact if the patient is alive.
Definitive Determination of the Prognostic Ability of 1p and 11q At baseline Addressed by a descriptive comparison of the EFS and OS rates for patients with 1p loss vs without 1p loss, and for those with unbalanced 11q vs normal 11q.
Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961 Up to 3 years Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients \< 1 yrs of age
Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS) Up to 10 years To test the predictive ability of the extent of surgical resection for EFS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection.
Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates Up to 10 years To test the predictive ability of the extent of surgical resection for OS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection.
Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate Up to 10 years To test for the association of the extent of surgical resection (CR vs \<CR) with surgical complications rate (complications of any kind vs no complications at all), a chi-square test will be performed.
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 Up to 3 years Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients \< 1 yrs of age.
Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma Up to 3 years Descriptive analyses of the proportion of stage 4S infants that experience a surgical or post-operative event.
Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment From baseline to up to 10 years Kaplan-Meier curves and lifetables of Event Free Survival (EFS) and Overall Survival (OS) rates will be generated to describe the outcome of the stage 4S infants unable to undergo biopsy.
- Secondary Outcome Measures
Name Time Method Second-event-free Survival (E2FS) From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse, progressive disease, secondary malignancy, or death; up to 3 years E2FS (from time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.
Second-Overall Survival From the time of the first progressive, non-metastatic event; up to 3 years OS (from the time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.
Biological Surrogate Markers At baseline and surgery Multivariable analyses will be performed to identify variables of prognostic interest.
Image Defined Risk Factor (IDRF) At baseline Percentage of patients with presence of one or more IDRFs will be calculated. IDRFs describe anatomic features which may make surgical resection more difficult.
Neurologic Symptoms At baseline Percentage of patients with neurologic symptoms will be calculated. Includes patients with paraspinal or intraspinal tumors, including epidural tumors with or without spinal cord compression. Neurologic symptoms include back or extremities neurologic symptoms, motor deficit, abnormal sensation, abnormal bladder/bowel sphincteric function, chronic pain in back or extremities, scoliosis, kyphosis, or clinically relevant/functional abnormality in size or contour of leg or foot.
Association Between Surgical Biopsy Technique With Adequacy of Tissue Acquisition for Biologic Studies, and With Complications Associated With the Biopsy Procedure During and after surgery A chi-square test will be performed.
Trial Locations
- Locations (189)
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Floating Hospital for Children at Tufts - New England Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸Miami, Florida, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Mountain States Tumor Institute at St. Luke's Regional Medical Center
🇺🇸Boise, Idaho, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Tulane Cancer Center Office of Clinical Research
🇺🇸Alexandria, Louisiana, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
West Virginia University Health Sciences Center - Charleston
🇺🇸Charleston, West Virginia, United States
Allan Blair Cancer Centre at Pasqua Hospital
🇨🇦Regina, Saskatchewan, Canada
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Maine Children's Cancer Program at Barbara Bush Children's Hospital
🇺🇸Scarborough, Maine, United States
Universitair Medisch Centrum St. Radboud - Nijmegen
🇳🇱Nijmegen, Netherlands
T.C. Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
🇺🇸Long Beach, California, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Lucile Packard Children's Hospital at Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Broward General Medical Center Cancer Center
🇺🇸Fort Lauderdale, Florida, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Walter Reed Army Medical Center
🇺🇸Washington, District of Columbia, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Kaplan Cancer Center at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
Memorial Cancer Institute at Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
🇺🇸Atlanta, Georgia, United States
Baptist-South Miami Regional Cancer Program
🇺🇸Miami, Florida, United States
MBCCOP - Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Keyser Family Cancer Center at Advocate Hope Children's Hospital
🇺🇸Oak Lawn, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Tripler Army Medical Center
🇺🇸Tripler AMC, Hawaii, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
CancerCare of Maine at Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
Breslin Cancer Center at Ingham Regional Medical Center
🇺🇸Lansing, Michigan, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Hackensack University Medical Center Cancer Center
🇺🇸Hackensack, New Jersey, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Albany Medical Center Hospital
🇺🇸Albany, New York, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
Overlook Hospital
🇺🇸Morristown, New Jersey, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Maimonides Cancer Center at Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Dayton Children's - Dayton
🇺🇸Dayton, Ohio, United States
Mercy Children's Hospital
🇺🇸Toledo, Ohio, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸Providence, Rhode Island, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo
🇺🇸Amarillo, Texas, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Baylor University Medical Center - Houston
🇺🇸Houston, Texas, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Fletcher Allen Health Care - University Health Center Campus
🇺🇸Burlington, Vermont, United States
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Royal Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Janeway Children's Health and Rehabilitation Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Children's Hospital of Western Ontario
🇨🇦London, Ontario, Canada
Starship Children's Health
🇳🇿Auckland, New Zealand
San Jorge Children's Hospital
🇵🇷Santurce, Puerto Rico
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
Legacy Emanuel Hospital and Health Center and Children's Hospital
🇺🇸Portland, Oregon, United States
Knight Cancer Institute at Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Children's Hospital Center for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Children's Hospital
🇺🇸Omaha, Nebraska, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Women's and Children's Hospital
🇦🇺North Adelaide, South Australia, Australia
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Schneider Children's Hospital
🇺🇸New Hyde Park, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Simmons Cooper Cancer Institute
🇺🇸Springfield, Illinois, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Sutter Cancer Center
🇺🇸Sacramento, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
Kaiser Permanente Medical Center - Oakland
🇺🇸Sacramento, California, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Advocate Lutheran General Cancer Care Center
🇺🇸Park Ridge, Illinois, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Mission Hospitals - Memorial Campus
🇺🇸Asheville, North Carolina, United States
Geisinger Cancer Institute at Geisinger Health
🇺🇸Danville, Pennsylvania, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Carilion Medical Center for Children at Roanoke Community Hospital
🇺🇸Roanoke, Virginia, United States
Madigan Army Medical Center - Tacoma
🇺🇸Tacoma, Washington, United States
Mary Bridge Children's Hospital and Health Center - Tacoma
🇺🇸Tacoma, Washington, United States
Providence Cancer Center at Sacred Heart Medical Center
🇺🇸Spokane, Washington, United States
Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Palmetto Health South Carolina Cancer Center
🇺🇸Columbia, South Carolina, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
M.D. Anderson Cancer Center at Orlando
🇺🇸Orlando, Florida, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
Lucille P. Markey Cancer Center at University of Kentucky
🇺🇸Lexington, Kentucky, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Greenville Hospital Cancer Center
🇺🇸Greenville, South Carolina, United States
Children's Hospital and Research Center Oakland
🇺🇸Oakland, California, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States