Comparing 123I-MIBG and 18F-MFBG Imaging in Patients With Newly Diagnosed, High Risk Neuroblastoma

PRIMARY OBJECTIVE:

I. To estimate the concordance in International Neuroblastoma Response Criteria (INRC) response designations at the end of induction as assessed by iobenguane I-123 (123I-MIBG) and florbenguane F18 (18F-MFBG) central reads in patients with high-risk stage L2 and stage M neuroblastoma.

SECONDARY OBJECTIVES:

I. To describe individual metastatic lesion response using 123I-MIBG and 18F-MFBG imaging at diagnosis and end-induction.

II. To describe concordance in central Curie score between 123I-MIBG and 18F-MFBG imaging.

III. To describe concordance in end of induction response designations (poor end-of induction response versus [vs.] good end-of induction response) as assessed by 123I-MIBG and 18F-MFBG in patients receiving high-risk therapy.

IV. To describe concordance as assessed by 123I-MIBG and 18F-MFBG in the INRC components of primary (soft tissue) tumor response and tumor response at metastatic soft tissue and bone sites in patients receiving high-risk therapy.

EXPLORATORY OBJECTIVES:

I. To describe concordance in International Neuroblastoma Risk Group Staging System (INRGSS) stage as assessed by 123I-MIBG and 18F-MFBG.

II. To describe the natural history of discordant lesions detected only by 18F-MFBG and not by 123I-MIBG in patients with high-risk neuroblastoma, and to describe additional interventions undertaken (including additional imaging, biopsies, and/or additional therapies) based on identification of discordant lesions.

III. To describe the change in standardized uptake value (SUV) of the primary and metastatic lesions on 18F-MFBG scans from diagnosis to end of induction.

IV. To evaluate the patient/family experience with 123I-MIBG and 18F-MFBG imaging.

V. To describe concordance between detection of disease using 123I-MIBG imaging (Curie score), 18F-MFBG imaging (Curie score) and the percentage of circulating tumor deoxyribonucleic acid (DNA) (as a continuous variable) testing during high-risk neuroblastoma therapy.

VI. To identify logistical barriers to successful imaging using 18F-MFBG. VII. To quantify inter-observer variability of Curie scores on 18F-MFBG and 123I-MIBG among central reviewers.

VIII. To describe acute toxicity of 18F-MFBG administration. IX. To estimate the progression free survival (PFS) and overall survival (OS) among eligible patients enrolled on the study.

OUTLINE:

Patients receive 18F-MFBG intravenously (IV) over 1 minute and undergo PET/CT or PET/MRI over 9-30 minutes at the time of each standard of care (SOC) 123I-MIBG scan (at the time of induction cycle 1, at the end of the last induction cycle, and at the time of first relapse/disease progression). Patients may undergo blood sample collection throughout the study.

Inclusion criteria

• Any age at diagnosis.
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular, unfavorable subtype) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites.
• Patients must have high-risk neuroblastoma defined as one of the following:

• Any age with International Neuroblastoma Risk Group (INRG) stage L2 or M and MYCN amplification.
• Age ≥ 547 days and INRG stage M regardless of biologic features.
• Age ≥ 547 days and INRG stage L2 with unfavorable histology.
• Patients must have newly diagnosed disease.
• Patients must have either measurable or evaluable disease by INRC.
• Patients observed or treated with a single cycle of chemotherapy per a low- or intermediate-risk neuroblastoma regimen (e.g. as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high-risk disease, but subsequently found to meet high-risk criteria will be eligible. These patients must enroll prior to the start of high-risk therapy.
• Patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
• Patients initially recognized to have high-risk disease must enroll prior to or within the first week after starting high-risk induction chemotherapy.
• Induction therapy as per a standard high-risk neuroblastoma induction regimen (examples include ANBL1531 arm A, ANBL2131 arm A, or ANBL2131 arm B) must be planned for patients to be eligible for this study.

Exclusion criteria

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events of radiation. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) at least 48 hours prior to and following all imaging studies. Abstinence is an acceptable method of birth control.
• Norepinephrine transporter (NET)-dependent agents: Many medications are known to interfere with uptake of NET-dependent agents. Investigators should use caution when prescribing these medications for patients undergoing procedures on this study. Medications that are known to substantially interfere with uptake of NET-dependent agents should be held if possible, based on patient condition 24 hours prior to each 18F-MFBG scan. These agents can be resumed immediately after each 18F-MFBG scan is completed. Patients who are receiving medications that are known to significantly interfere with uptake of NET-dependent agents (primarily tricyclic antidepressants, psychostimulants, and antihypertensives) and for whom these medications cannot be safely withheld before the start of study procedures will not be eligible.
• The patient has a known or suspected history of significant allergic reaction or anaphylaxis to any components of the 18F-MFBG or 123I-MIBG imaging agents.
• Patients who will require sedation or anesthesia only for 18F-MFBG imaging.

• Note: Patients who need anesthesia will be required to have 18F-MFBG imaging combined with other scans or procedures necessary for clinical care (ex: MRI, bone marrow aspirate/biopsies, line placement).
• Patients will be able to enroll prior to baseline 123I-MIBG imaging. However, patients who have had their baseline standard of care 123I-MIBG imaging prior to enrollment who have known MIBG non-avid disease are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.