An Investigational Scan (68Ga-DOTATATE PET/CT) in Diagnosing Pediatric Metastatic Neuroendocrine Tumors

Study Overview
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Brief Summary
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This trial studies how well an investigational scan called 68Ga-DOTATATE PET/CT works in diagnosing pediatric patients with neuroendocrine tumors that have spread to other places in the body (metastatic). A neuroendocrine tumor is an abnormal growth of neuroendocrine cells, which are cells resembling nerve cells and hormone-producing cells. 68Ga-DOTATATE is a radioactive substance called a radiotracer that when used with PET/CT scans, may work better than standard of care MIBG scans in diagnosing pediatric metastatic neuroendocrine tumors and targeting them with radiation therapy.

Detailed Description
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PRIMARY OBJECTIVE: I. To estimate the difference in radiation therapy (RT) target volume definition between gallium Ga 68-DOTATATE (68Ga-DOTATATE) PET/CT and iobenguane (metaiodobenzylguanidine [MIBG]). SECONDARY OBJECTIVES: I. To estimate the difference in metastatic tumor burden as detected by 68Ga-DOTATATE PET/CT and MIBG. II. To estimate the difference in metabolic activity between tumors diagnosed on 68Ga-DOTATATE PET/CT and MIBG. III. To evaluate patterns of failure after RT in association with 68Ga-DOTATATE PET/CT and MIBG. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients with newly diagnosed high-risk neuroendocrine cancer receive 68Ga-DOTATATE intravenously (IV) and undergo PET/CT over 20-30 minutes at diagnosis (before any treatment) and at the time of radiation treatment planning. COHORT B: Patients with previously diagnosed high-risk neuroendocrine cancer receive 68Ga-DOTATATE IV and undergo PET/CT over 20-30 minutes at the time of radiation treatment planning. After completion of study, patients are followed up every 3 months for up to 2 years.

Official Title
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Utility of Gallium-68-DOTA-Octreotate PET/CT in the Characterization of Pediatric Neuroendocrine Tumors

Conditions
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Ganglioneuroblastoma, Ganglioneuroma, Neuroblastoma

Intervention / Treatment
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* Procedure: Computed Tomography
* Drug: Gallium Ga 68-DOTATATE
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age =< 30 years Histological confirmation of neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. High-risk neuroblastoma requiring consolidative RT, as determined by the treating radiation oncologist. Eastern Cooperative Oncology Group (ECOG) performance status 0-3. Planned for radiation planning and RT at enrolling institution. Documented negative pregnancy test prior to induction chemotherapy, for women of childbearing age within =< 7 days prior to registration. Signed written informed consent from patient, parent, and/or legal guardian. Willing to return to enrolling institution for follow-up imaging and clinical evaluation, or willing to send follow-up imaging and clinical notes to enrolling institution (during the observation phase of the study). Exclusion Criteria: Pregnant women, nursing women who refuse to stop breastfeeding, or men/women of childbearing age who are unwilling to use an effective birth control method. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Immunocompromised patients and patients known to be human immunodeficiency virus positive and currently receiving antiretroviral therapy. NOTE: Patients known to be human immunodeficiency virus positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A (68Ga-DOTATATE, PET/CT)<br>Patients with newly diagnosed high-risk neuroendocrine cancer receive 68Ga-DOTATATE intravenously (IV) and undergo PET/CT over 20-30 minutes at diagnosis (before any treatment) and at the time of radiation treatment planning. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Drug: Gallium Ga 68-DOTATATE<br>* Given IV<br>* Other names: Gallium-68 DOTA-DPhe1, Tyr3-octreotate;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|
| Experimental: Cohort B (68Ga-DOTATATE, PET/CT)<br>Patients with previously diagnosed high-risk neuroendocrine cancer receive 68Ga-DOTATATE IV and undergo PET/CT over 20-30 minutes at the time of radiation treatment planning. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Drug: Gallium Ga 68-DOTATATE<br>* Given IV<br>* Other names: Gallium-68 DOTA-DPhe1, Tyr3-octreotate;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in radiation treatment target volume definition between 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) and iobenguane (MIBG) | Will analyze the data descriptively in lieu of hypothesis testing. However, each metastatic lesion will be analyzed independently. Will report the mean and standard deviation of the difference between target tumor volumes. For patients with more than one metastasis, will compute the difference in the sum of the target volumes for all metastases. | From baseline to the time of radiation treatment planning (up to 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of agreement between MIBG and 68Ga-DOTATATE PET/CT in identifying neuroendocrine tumors | Will calculate the proportion of metastatic tumors detected by MIBG that are also detected by 68Ga-DOTATATE PET/CT. Each metastatic lesion will be considered an independent data point. A 95% confidence interval will be included using the Clopper-Pearson method. | At diagnosis and during the radiation treatment (RT) planning period (up to 3 months) | 
| Tumor metabolic activity of 68Ga-DOTATATE PET/CT compared to MIBG | Will perform some descriptive analyses to note the differences between MIBG and 68Ga-DOTATATE PET/CT. This may include measuring the difference in the number of metastatic sites per patient. Each metastatic lesion will be considered an independent data point. | At diagnosis and during the RT planning period (up to 3 months) | 
| Patterns of failure after RT | Will evaluate patterns of failure after RT and associate with MIBG and 68Ga-DOTATATE PET/CT using two-year relapse rates. Relapse is defined as an increase in treated lesion(s) and/or new tumor per the progressive disease category of the International Neuroblastoma Response Criteria. Two-year cumulative incidence of relapse from first day of RT for the four categories listed above will be calculated considering death as a competing risk. Each relapse site will be considered an independent event. | Up to 2 years |