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

NCT ID: NCT01440283

Last Updated: 2016-03-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2015-03-31

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.

Conditions

Abdominal Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Other Intervention Names

IMRT

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chia-Ho Hua, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NBIMRT

Identifier Type: -

Identifier Source: org_study_id