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

This study has been terminated.
Sponsor:
Collaborator:
Mayo Clinic
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01440283
First received: September 20, 2011
Last updated: February 3, 2016
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Abdominal Neuroblastoma
Radiation: Intensity Modulated Radiation Therapy (IMRT)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Percentage of Participants Who Failed to Reach Local-regional Control [ Time Frame: 2 years after last patient enrollment ] [ Designated as safety issue: No ]
    Measured from start of radiation therapy to date of local-regional failure or last follow-up.

  • Pattern of Local-regional Failure. [ Time Frame: 2 years after last patient enrollment ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and approximately 2 weeks following initiation of irradiation. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and approximately 2 weeks following initiation of irradiation. ] [ Designated as safety issue: No ]
    Obtain target tissue motion-defining data which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue.


Enrollment: 14
Study Start Date: September 2011
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

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)

Radiation: Intensity Modulated Radiation Therapy (IMRT)
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.
Other Name: IMRT

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.

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440283

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Mayo Clinic
Investigators
Principal Investigator: Chia-Ho Hua, PhD St. Jude Children's Research Hospital
  More Information

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01440283     History of Changes
Other Study ID Numbers: NBIMRT 
Study First Received: September 20, 2011
Results First Received: November 9, 2015
Last Updated: February 3, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Neuroblastoma
Radiation Therapy

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 28, 2016