A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) in High Risk Abdominal Neuroblastoma
Condition: Abdominal Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: Intensity Modulated Radiation Therapy (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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 6 Months
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Neuroblastoma; Radiation Therapy

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.
    

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.