Phase II Study of Proton Radiation Therapy for Neuroblastoma

This research study is evaluating a therapy called proton beam radiation therapy (PBRT) as a possible treatment for neuroblastoma.

Neuroblastoma most commonly occurs in and around the adrenal glands, which are located at the top of the kidneys. However, it can also occur in other areas where groups of nerve cells exist, such as other areas of the abdomen, neck and near the spine.

Conventional radiation therapy with photons is used as standard treatment for many patients with neuroblastic tumors. In this research study, the investigators are looking at another type of radiation called proton radiation which is known to spare surrounding tissues and organs from unnecessary radiation. Proton radiation delivers radiation to the area requiring radiation. This may reduce side effects that patients would normally experience with standard radiation therapy or other means of delivering proton radiation therapy.

In this research study, the investigators are evaluating the effectiveness of using proton radiation delivered to reduce side effects associated with radiation treatment. The investigators will also be assessing the late side effects experienced by participants in each treatment group.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma; Ganglioneuroblastoma
• Intervention / Treatment: Radiation: Proton Beam Radiation Therapy

Detailed Description

Proton radiation will be delivered daily for 3-4 weeks, depending on the dose prescribed by study doctor. Treatment is delivered (Monday - Friday) for 5 days (no weekends or holidays). Each treatment the participant will lie on a table for 30-45 minutes.

The radiation therapy will be outpatient at Massachusetts General Hospital.

During radiation therapy, the participant will have the following weekly assessments and procedures:

• Physical Exam
• Assess for any side effects
• Routine blood tests (weekly or at least every other week)

Post-treatment Follow Up Visit (s):

The participant will be asked to return to the clinic 3-6 months after their last dose of radiation therapy and then annually for up to 5 years for the following procedures:

• Medical History
• Physical Exam
• Diagnostic Imaging
• Assess for side effects
• Lung Function Tests (if required)
• MUGA or ECHO (if required)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shannon M MacDonald, MD; Phone Number: 617-643-7250; Email: smacdonald@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Shannon M. MacDonald, MD; Phone Number: 617-643-7250; Email: smacdonald@partners.org
      • Principal Investigator: Shannon M. MacDonald, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically confirmed neuroblastoma or ganglioneuroblastoma or elevated urinary catecholamine metabolites. If tumor tissue was obtained, pathological review of surgical specimen at the Massachusetts General Hospital or other DF/HCC institution is required, but preliminary report only required prior to enrollment. If no tumor tissue was obtained, urinary catecholamine metabolites are required.
• Participants do not need to have measurable disease at the time of radiation. Age ≥ 3 and ≤ 25 years at the time of diagnosis because this study evaluates this disease entity in the pediatric population which may differ from the adult population.
• Life expectancy of greater than 12 months.
• ECOG performance status ≤2 (Karnofsky ≥60%, Lansky ≥60%, see Appendix A).
• Diagnostic Imaging MRI and/or CT of the area to be treated within 8 weeks of any treatment. Baseline bone marrow biopsy and bone scan (with 99mTc-diphosphonate or MIBG scan (131I-MIBG or 123I-MIBG) from time of original diagnosis is required.
• Because radiation is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability of the patient or the patient's legal guardian to understand and the willingness to sign a written informed consent document.
• Participants or their legal guardian must sign consent prior to the initiation of radiation therapy.

Exclusion Criteria:

• Patients will be ineligible if any prior therapeutic radiation therapy > 500 cGy has been delivered.
• Patients will be ineligible if chemotherapy was completed ≥ 1 year from the planned start date of radiation therapy or if the patient is referred for radiation therapy after a relapse following a regimen with chemotherapy alone.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
• Pregnant females are excluded. Women of childbearing age/menstruating must have a negative pregnancy test prior to initiation of radiation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proton Beam Radiation Therapy (PBRT); Proton radiation will be delivered daily for 3-4 weeks, depending on the dose prescribed by study doctor. Treatment is delivered (Monday - Friday) for 5 days (no weekends or holidays). Each treatment the participant will lie on a table for 30-45 minutes.	Radiation: Proton Beam Radiation Therapy; Proton radiation will be delivered daily for 3-4 weeks, depending on the dose prescribed by study doctor. Treatment is delivered (Monday - Friday) for 5 days (no weekends or holidays). Each treatment the participant will lie on a table for 30-45 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe late complications of radiation therapy delivered with proton radiotherapy in place of photon radiation for patients with neuroblastoma	To describe late complications of radiation therapy delivered with proton radiotherapy in place of photon radiation for patients with neuroblastoma. Specifically, cardiac, pulmonary, gastrointestinal, endocrine, growth and second malignancies will be described.	5 years
To evaluate acute and subacute toxicities of proton radiotherapy in place of photon radiation for patients with neuroblastoma.	To evaluate acute and subacute toxicities of proton radiotherapy in place of photon radiation for patients with neuroblastoma. Specifically, nausea, vomiting, diarrhea, radiation pneumonitis and skin toxicity will be described.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	10 years
Overall survival rates	10 Years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Shannon M. MacDonald, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 10, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimated): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Neuroblastoma; Childhood neuroblastoma; Ganglioneuroblastoma; Pediatric neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma; Ganglioneuroblastoma; Therapeutics; Radiotherapy; Heavy Ion Radiotherapy; Proton Therapy
• Other Study ID Numbers: 13-443