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A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma

Primary Purpose

Abdominal Neuroblastoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Intensity Modulated Radiation Therapy (IMRT)
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Abdominal Neuroblastoma focused on measuring Neuroblastoma, Radiation Therapy

Eligibility Criteria

6 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Mucositis ≤ Grade 2
  • Patient stable on room air
  • Albumin > 3 g/dL without albumin infusions for 1 week
  • Serum creatinine should be < 1.5 x normal for age
  • Lansky score >60

  • Risk Strata Eligibility: Patients between 6 months and 18 years of age with newly diagnosed abdominal primary, high-risk neuroblastoma defined as one of the following:

    • International agreement on staging (INSS) stage 2a or 2b with N-myc (MYCN) amplification (greater than four-fold increase in (MYCN) signals as compared to reference signals), regardless of age or additional biologic features
    • INSS stage 3 with either MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features, or for age > 18 months with unfavorable pathology, regardless of MYCN status
    • INSS stage 4 with MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features, or for age >18 months with unfavorable pathology, regardless of MYCN status
    • INSS stage 4S with MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features

  • Exceptional Cases Still Considered Eligible:

    • Prior palliative radiotherapy if not related to the primary site, however, children receiving definitive radiotherapy as a part of the pre-enrollment regimen are ineligible. Prior treatment regimen must follow the guidelines of an applicable high-risk neuroblastoma regimen. Slight variations from this timeframe are acceptable based on recovery of blood counts or other concerns left to the discretion of the treating radiation oncologist.
    • Patients receiving surgical management elsewhere are still considered eligible to enroll on protocol therapy for assessment of the primary local control objective, renal motion and toxicity assessment. Target motion objectives may be excluded from the analysis of these patients.

Exclusion Criteria

  • Patients who have received prior definitive radiotherapy at or adjacent to the primary abdominal tumor bed.
  • Patients who are unable to cooperate with acquisition of 4-dimensional computed tomography (4DCT), computed tomography (CT) or magnetic resonance imaging- (MRI)-based imaging procedures.
  • Patients with known brain metastases.
  • Any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
  • Pregnant women.
  • Mediastinal primary tumors.
  • Patients receiving surgery elsewhere, or at St. Jude within 3 months prior to study activation, are excluded from assessment of target and motion objectives. However they are still eligible to enroll for assessment of the primary objective, renal motion and toxicity.

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen will be eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients will begin the planning process for abdominal irradiation. Interventions: Intensity Modulated Radiation Therapy (IMRT)

Outcomes

Primary Outcome Measures

Percentage of Participants Who Failed to Reach Local-regional Control
Measured from start of radiation therapy to date of local-regional failure or last follow-up.
Pattern of Local-regional Failure.
Categorical measurements of local-regional failure.

Secondary Outcome Measures

Quantify the Range of Organ Movement During the Breathing Phase Measured by 4-dimensional MRI (4DMRI) and 4DCT.
Normal tissue motion-defining measurements were obtained which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue. Participants underwent CT simulation and 4D-CT acquisition as well as real-time dynamic 4D MRI prior to the start of radiation therapy (RT), and a subsequent repeat 4D-CT was obtained approximately 2 weeks after the start of RT. The imaging position was supine with general anesthesia. Renal edges were marked in a customized graphical interface for each imaging series with the image resolution determining the minimum motion extent. Vectors of renal edge motion were quantified in the anterior-posterior (A-P), medial-lateral (M-L), and superior-inferior (S-I) dimensions. The motion extent derived from the MRI dataset was considered in defining the margins for RT treatment planning.
Quantify (in mm/cm) the Range of Target Movement During the Breathing Phase Measured by 4DMRI and 4DCT.
Obtain target tissue motion-defining data which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue.

Full Information

First Posted
September 20, 2011
Last Updated
February 3, 2016
Sponsor
St. Jude Children's Research Hospital
Collaborators
Mayo Clinic
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1. Study Identification

Unique Protocol Identification Number
NCT01440283
Brief Title
A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma
Official Title
A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Terminated
Study Start Date
September 2011 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
Mayo Clinic

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
High risk neuroblastoma (NB) is an aggressive, prevalent non-brain cancer derived from nerve cells of the body. It mostly affects infants, and more children die from this tumor each year than are cured. Standard therapy includes a combination of chemotherapy, surgery, bone marrow transplant, radiation and immunotherapy. NB is very sensitive to radiation, but due to it's aggressive spread pattern, radiation use is currently limited by toxicity. This study seeks to improve delivery of radiation to reduce toxicity by quantifying outcomes, and measuring differences in renal toxicity and organ motion so that radiation can be focused more effectively against tumor while sparing normal tissues and reducing side-effects.
Detailed Description
Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen will be eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients will begin the planning process for abdominal irradiation; this requires multiple baseline studies, including computed tomography (CT), magnetic resonance imaging (MRI), renal scintigraphy, and bloodwork. Most of these tests will be repeated on a varying schedule over the five year follow-up period of the protocol, in order to evaluate the impact of conformal radiotherapy on intra-abdominal tissues. Intensity modulated radiation therapy (IMRT) delivery will follow current conventional volume-targeting guidelines, however, appropriate application within the abdomen will be determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease is required. Concurrent neuro-hormonal tests, cytokine analyses, functional and morphologic imaging will generate novel data describing the acute and chronic effects of radiotherapy within the abdomen. NOTE: This study is currently closed to accrual, however, it is expected to re-open to accrual later in 2015.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Abdominal Neuroblastoma
Keywords
Neuroblastoma, Radiation Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Patients with high-risk abdominal neuroblastoma who receive any high-risk neuroblastoma treatment regimen will be eligible to enroll prior to surgical resection of the primary tumor. Following implantation of fiducial markers within the tumor bed and autologous hematopoietic rescue, patients will begin the planning process for abdominal irradiation. Interventions: Intensity Modulated Radiation Therapy (IMRT)
Intervention Type
Radiation
Intervention Name(s)
Intensity Modulated Radiation Therapy (IMRT)
Other Intervention Name(s)
IMRT
Intervention Description
IMRT delivery will follow current conventional volume-targeting guidelines, however, appropriate application within the abdomen will be determined by ascertaining intra-abdominal organ motion and the potential for reducing normal tissue dose, while simultaneously increasing dose delivered to target tissues, particularly when dose escalation for gross residual disease is required. Concurrent neuro-hormonal tests, cytokine analyses, functional and morphologic imaging will generate novel data describing the acute and chronic effects of radiotherapy within the abdomen.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Failed to Reach Local-regional Control
Description
Measured from start of radiation therapy to date of local-regional failure or last follow-up.
Time Frame
2 years after last patient enrollment
Title
Pattern of Local-regional Failure.
Description
Categorical measurements of local-regional failure.
Time Frame
2 years after last patient enrollment
Secondary Outcome Measure Information:
Title
Quantify the Range of Organ Movement During the Breathing Phase Measured by 4-dimensional MRI (4DMRI) and 4DCT.
Description
Normal tissue motion-defining measurements were obtained which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue. Participants underwent CT simulation and 4D-CT acquisition as well as real-time dynamic 4D MRI prior to the start of radiation therapy (RT), and a subsequent repeat 4D-CT was obtained approximately 2 weeks after the start of RT. The imaging position was supine with general anesthesia. Renal edges were marked in a customized graphical interface for each imaging series with the image resolution determining the minimum motion extent. Vectors of renal edge motion were quantified in the anterior-posterior (A-P), medial-lateral (M-L), and superior-inferior (S-I) dimensions. The motion extent derived from the MRI dataset was considered in defining the margins for RT treatment planning.
Time Frame
Baseline and approximately 2 weeks following initiation of irradiation.
Title
Quantify (in mm/cm) the Range of Target Movement During the Breathing Phase Measured by 4DMRI and 4DCT.
Description
Obtain target tissue motion-defining data which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue.
Time Frame
Baseline and approximately 2 weeks following initiation of irradiation.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Mucositis ≤ Grade 2 Patient stable on room air Albumin > 3 g/dL without albumin infusions for 1 week Serum creatinine should be < 1.5 x normal for age Lansky score >60 Risk Strata Eligibility: Patients between 6 months and 18 years of age with newly diagnosed abdominal primary, high-risk neuroblastoma defined as one of the following: International agreement on staging (INSS) stage 2a or 2b with N-myc (MYCN) amplification (greater than four-fold increase in (MYCN) signals as compared to reference signals), regardless of age or additional biologic features INSS stage 3 with either MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features, or for age > 18 months with unfavorable pathology, regardless of MYCN status INSS stage 4 with MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features, or for age >18 months with unfavorable pathology, regardless of MYCN status INSS stage 4S with MYCN amplification (greater than four-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features Exceptional Cases Still Considered Eligible: Prior palliative radiotherapy if not related to the primary site, however, children receiving definitive radiotherapy as a part of the pre-enrollment regimen are ineligible. Prior treatment regimen must follow the guidelines of an applicable high-risk neuroblastoma regimen. Slight variations from this timeframe are acceptable based on recovery of blood counts or other concerns left to the discretion of the treating radiation oncologist. Patients receiving surgical management elsewhere are still considered eligible to enroll on protocol therapy for assessment of the primary local control objective, renal motion and toxicity assessment. Target motion objectives may be excluded from the analysis of these patients. Exclusion Criteria Patients who have received prior definitive radiotherapy at or adjacent to the primary abdominal tumor bed. Patients who are unable to cooperate with acquisition of 4-dimensional computed tomography (4DCT), computed tomography (CT) or magnetic resonance imaging- (MRI)-based imaging procedures. Patients with known brain metastases. Any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease). Pregnant women. Mediastinal primary tumors. Patients receiving surgery elsewhere, or at St. Jude within 3 months prior to study activation, are excluded from assessment of target and motion objectives. However they are still eligible to enroll for assessment of the primary objective, renal motion and toxicity.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chia-Ho Hua, PhD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude

Learn more about this trial

A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma

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