Treatment for high-risk neuroblastoma in children using 67Cu-SARTATE

67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk Neuroblastoma: A Multi-center, Dose-escalation, Open-label, Non-randomized, Phase 1-2a Theranostic Clinical Trial

This study is testing a new treatment using 67Cu-SARTATE for children with high-risk neuroblastoma to see if it is safe and effective in helping them.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Sex: All
• Sponsor: Clarity Pharmaceuticals Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 8 sites (Phoenix, Arizona and 7 other locations)
• Trial ID: NCT04023331 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of 67Cu-SARTATE peptide receptor radionuclide therapy in pediatric patients with high-risk neuroblastoma. It employs an adaptive trial design, allowing modifications based on accumulating data, and a personalized approach to determine treatment intervals and cycles for each patient. The study consists of two phases: a dose escalation phase using a modified 3+3 design and a cohort expansion phase for additional subjects once the maximum tolerated dose is established. Participants may receive up to four therapy cycles based on their response to treatment.

Who should consider this trial

Good fit: Ideal candidates include pediatric patients with high-risk neuroblastoma or those whose intermediate-risk neuroblastoma has relapsed or progressed to high-risk.

Not a fit: Patients with low-risk neuroblastoma or those who have not progressed after standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for children with high-risk neuroblastoma who have limited alternatives.

How similar studies have performed: Other studies using peptide receptor radionuclide therapy have shown promise, but this specific approach with 67Cu-SARTATE is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Participant is able and willing to provide informed consent (≥18 years), or informed consent is obtained by the parent or legal guardian for minor participants, with the minor providing age appropriate assent, according to local law and regulations;
2. Life expectancy ≥ 12 weeks;
3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has relapsed or progressed to high-risk, with failure to achieve complete response with standard therapy (defined as at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, or according to a standard high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to receive standard treatment OR who are intolerant to standard treatment;
4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the Investigator or treating Sub-Investigator;
5. Adequate liver function as defined by the following laboratory values obtained within 28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 x upper limit of normal (ULN);
6. Adequate renal function;
7. Adequate laboratory parameters: Absolute neutrophil count \> 1.0 x 10 9/L; Platelet count \> 50 x 10 9/L; Total bilirubin \<1.5 x ULN;
8. Karnofsky or Lansky performance status ≥50;
9. All participants must have a hematopoietic stem cell product available (minimum CD34+ cell dose is ≥2 x 10 6 cells/kg);
10. Sexually active participants of reproductive potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is considered acceptable;
11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than that of the liver in order to move on to the therapy phase of the study.

Exclusion Criteria:

1. Participants with disease of any major organ system that would compromise their ability to tolerate therapy, as deemed by the Investigator or treating Sub-Investigator;
2. Any other active malignancy, or a history of prior malignancy within the past 3 years;
3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance, oxygen requirement, clinically significant cardiac dysfunction;
4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the administration of 64Cu-SARTATE;
6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney within 12 months prior to the administration of 64Cu-SARTATE;
7. Administration of any investigational agents within 21 days prior to administration of 64Cu-SARTATE;
8. Treatment with long acting somatostatin analogues (administered within 28 days prior to the administration of 64Cu-SARTATE), or short acting somatostatin analogues (administered within 24 hours prior to the administration of 64Cu-SARTATE);
9. Known sensitivity or allergy to somatostatin analogues;
10. Previous peptide receptor radionuclide therapy (PRRT);
11. Female participants who are pregnant or lactating;
12. Participants who are on hemodialysis;
13. QTc interval ≥ 0.45 seconds as measured by Screening ECG;
14. Participants with uncontrolled infection(s);
15. Any medical condition which the Investigator feels may interfere with the procedures or evaluations of the study;
16. Participants 12 months and younger will be excluded from cohorts where the planned single or cumulative administered activity is modelled to deliver a radiation dose to the marrow that exceeds 2 Gy.

Where this trial is running

Phoenix, Arizona and 7 other locations

• Phoenix Children's Hospital — Phoenix, Arizona, United States (Recruiting)
• Washington University School of Medicine — Saint Louis, Missouri, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Cincinnati Children's Hospital Medical Centre — Cincinnati, Ohio, United States (Recruiting)
• Medical University of South Carolina — Charleston, South Carolina, United States (Recruiting)
• University of Texas Southwestern Medical Centre — Dallas, Texas, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• University of Wisconsin — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Study coordinator: Clarity Pharmaceuticals

Conditions Neuroblastoma; Relapsed Neuroblastoma; Refractory Neuroblastoma