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

Phase 2

Terminated

Conditions: Abdominal Neuroblastoma

Interventions: Radiation: Intensity Modulated Radiation Therapy (IMRT)

Registration Number: NCT01440283

Lead Sponsor: St. Jude Children's Research Hospital

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 14

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Intensity Modulated Radiation Therapy (IMRT)	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)

Primary Outcome Measures

Name	Time	Method
Pattern of Local-regional Failure.	2 years after last patient enrollment	Categorical measurements of local-regional failure.
Percentage of Participants Who Failed to Reach Local-regional Control	2 years after last patient enrollment	Measured from start of radiation therapy to date of local-regional failure or last follow-up.

Secondary Outcome Measures

Name	Time	Method
Quantify the Range of Organ Movement During the Breathing Phase Measured by 4-dimensional MRI (4DMRI) and 4DCT.	Baseline and approximately 2 weeks following initiation of irradiation.	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.	Baseline and approximately 2 weeks following initiation of irradiation.	Obtain target tissue motion-defining data which can guide future more conformal therapeutic regimens incorporating smaller volumes of uninvolved tissue.