Peptide Receptor Radionuclide Therapy for Neuroblastoma

Recruiting at 9 trial locations

Overseen By Clarity Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Clarity Pharmaceuticals Ltd

Must not be taking: Somatostatin analogues, Investigational agents

Disqualifiers: Active malignancy, Cardiac failure, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 67Cu-SARTATE, a type of peptide receptor radionuclide therapy, to determine its safety and effectiveness for children with high-risk neuroblastoma, a cancer affecting certain nerve cells. The trial administers this experimental treatment through an IV to evaluate its effectiveness against the cancer. Children with neuroblastoma that has not responded well to standard treatments might be suitable candidates for this study. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have chemotherapy, anti-cancer cytokine therapy, immunotherapy, or radiotherapy within 2 weeks before the trial, and certain other treatments have specific time restrictions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 67Cu-SARTATE is generally safe and well-tolerated. In earlier studies with adult cancer patients, it demonstrated a good safety record. For children with high-risk neuroblastoma, no problems occurred when 67Cu-SARTATE was administered at the highest dose tested. This suggests the treatment is likely safe, but it is important to remember that this study remains in the early stages. The results so far are promising, but ongoing research will provide more information about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for neuroblastoma, which often involve chemotherapy and radiation, 67Cu-SARTATE offers a targeted approach using Peptide Receptor Radionuclide Therapy (PRRT). This therapy harnesses a radioactive isotope, copper-67, to deliver radiation directly to cancer cells through a peptide, potentially minimizing damage to healthy tissues. Researchers are excited about this treatment because it could provide a more precise and less toxic alternative, with the potential to improve outcomes for patients with neuroblastoma.

What evidence suggests that 67Cu-SARTATE might be an effective treatment for neuroblastoma?

Research has shown that 67Cu-SARTATE, which participants in this trial may receive, may help treat high-risk neuroblastoma, a cancer often found in children. In animal studies, 67Cu-SARTATE significantly increased survival rates, especially when used early in treatment. These early results suggest that the treatment might effectively target and shrink cancer cells. Although studies in humans are still ongoing, the initial findings are promising and may offer benefits for patients with this aggressive cancer. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for pediatric patients with high-risk neuroblastoma that's relapsed or not responding to standard treatments. They must have a life expectancy of at least 12 weeks, adequate organ function, and a minimum performance status of 50. Participants need available stem cells for transplant and must use effective birth control if applicable.

Inclusion Criteria

I can do most activities but may need help.

My neuroblastoma is high-risk and hasn't fully responded to standard treatments.

My scan shows a lesion as active as or more than my liver.

Exclusion Criteria

I received a specific radioactive treatment within the last 8 weeks.

My major organs are healthy enough to handle the treatment.

I have undergone peptide receptor radionuclide therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Participants receive a single administration of 67Cu-SARTATE as an IV infusion with dose escalation based on cohort allocation. Dose Limiting Toxicities are monitored for 6 weeks post administration.

6 weeks

Cohort Expansion

Participants receive at least 2 therapy cycles of 67Cu-SARTATE at the Maximum Tolerated Dose (MTD) level. Additional therapy cycles may be offered based on therapeutic benefit.

Variable, up to 4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments up to 36 months following the first dose.

36 months

No in-person visits required

What Are the Treatments Tested in This Trial?

Interventions

• 64Cu-SARTATE
• 67Cu-SARTATE

Trial Overview The study tests the safety and effectiveness of a therapy called 67Cu-SARTATE in children with aggressive neuroblastoma. Patients first undergo a scan using 64Cu-SARTATE to ensure their tumors absorb the drug well enough before receiving the actual treatment.

How Is the Trial Designed?

Group I: 67Cu-SARTATE Experimental Treatment 2 Interventions

64Cu-SARTATE - patients will receive a bolus injection of 64Cu-SARTATE during screening, and following each 67Cu-SARTATE Therapy Cycle, at a rate of 2.0 MBq/kg. 67Cu-SARTATE - In the dose escalation phase, patients will receive a single administration of 67Cu-SARTATE as an IV infusion (dose will be determined based on cohort allocation). In the expansion phase, patients will receive at least 2 administrations of 67Cu-SARTATE at the MTD/MFD level as a slow IV infusion. Participants in either phase of the study that demonstrate therapeutic benefit following treatment with 67Cu-SARTATE at any dose may be offered additional Therapy Cycles (each participant may receive a maximum of 4 Therapy Cycles in total).

67Cu-SARTATE is already approved in United States for the following indications:

Approved in United States as 67Cu-SARTATE for:

• Neuroblastoma

Who Is Running the Clinical Trial?

Clarity Pharmaceuticals Ltd

Lead Sponsor

Trials

11

Recruited

720+

Published Research Related to This Trial

The study demonstrated that [64Cu]Cu-SARTATE effectively targets and detects neuroblastoma tumors expressing the SSTR2 receptor, with significant uptake in viable tumor regions and rapid clearance from non-target tissues, particularly the kidneys.

Therapeutic use of [67Cu]Cu-SARTATE starting two weeks after tumor cell inoculation significantly extended survival in a preclinical model of neuroblastoma by an average of 13 days, highlighting its potential as a treatment for minimal residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection and therapy of neuroblastoma minimal residual disease using [64/67Cu]Cu-SARTATE in a preclinical model of hepatic metastases. Dearling, JLJ., van Dam, EM., Harris, MJ., et al.[2021]

The study highlights the potential of using [64/67Cu]Cu-SARTATE as a theranostic tool for detecting and treating SSTR2-positive neuroblastoma in pediatric patients, particularly for addressing minimal residual disease after initial therapy.

The authors propose a new therapy-dosimetric equation to improve the estimation of therapeutic dosages based on initial diagnostic scans, which could enhance the effectiveness of future clinical applications of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An abbreviated therapy-dosimetric equation for the companion diagnostic/therapeutic [64/67Cu]Cu-SARTATE. Laffon, E., de Clermont, H., Marthan, R.[2021]

The peptide-linked copper chelator DOTA-R1-F(ab')2 showed superior performance in targeting neuroblastoma tumors, with higher tumor uptake and better tumor-to-tissue ratios compared to other conjugates in a mouse model.

CPTA-R1-F(ab')2 demonstrated improved biodistribution by reducing radioactivity in the kidneys, which may enhance safety and efficacy in therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A triglycine linker improves tumor uptake and biodistributions of 67-Cu-labeled anti-neuroblastoma MAb chCE7 F(ab')2 fragments. Zimmermann, K., Gianollini, S., Schubiger, PA., et al.[2019]

The monoclonal antibody chCE7, when labeled with Copper-67, demonstrated high and stable tumor uptake in neuroblastoma models, with significant increases in tumor-to-blood ratios over time, indicating effective targeting of the cancer cells.

Using the novel DO3A ligand for labeling chCE7 F(ab')2 fragments resulted in a fourfold increase in tumor uptake and a fourfold reduction in kidney radioactivity compared to the previous CPTA ligand, suggesting improved safety and efficacy for potential therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor uptake and metabolism of copper-67-labeled monoclonal antibody chCE7 in nude mice bearing neuroblastoma xenografts. Novak-Hofer, I., Zimmermann, K., Maecke, HR., et al.[2015]

Copper-64 and Copper-67 isotopes are promising for cancer treatment and imaging, with Copper-64 suitable for PET imaging and Copper-67 for SPECT imaging and radiotherapy, thanks to their favorable decay characteristics.

Recent advancements in the production of Copper-67 have provided a reliable source with high purity, enhancing the potential for copper-based radiopharmaceuticals in diagnosing and treating various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in 64Cu/67Cu-Based Radiopharmaceuticals. Krasnovskaya, OO., Abramchuck, D., Erofeev, A., et al.[2023]

The study demonstrated that 64Cu-labeled ch14.18 antibodies can specifically target neuroblastoma tumors, achieving a high accumulation rate of 31.6% ID/g in preclinical models, indicating their potential efficacy for targeted therapy.

Clinical PET/MRI scans using the radiolabeled antibodies successfully visualized neuroblastoma metastases in a patient, suggesting that this theranostic approach could be a valuable tool for therapy planning in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational immunoPET imaging using a radiolabeled GD2-specific antibody in neuroblastoma. Schmitt, J., Schwenck, J., Maurer, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04023331

Study Details | NCT04023331 | 67Cu-SARTATE™ Peptide ... The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric patients with high-risk neuroblastoma. ... This is an 'adaptive trial'.

2. claritypharmaceuticals.com claritypharmaceuticals.com/news/cl04_c4_fp/

First participant treated in the highest dose cohort ... The CL04 trial (NCT04023331) 1 is a theranostic trial evaluating 64 Cu/ 67 Cu SARTATE for diagnosis and treatment of high-risk neuroblastoma, an aggressive ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/61/supplement_1/292

Cu-67-SARTATE significantly extends survival in a hepatic ... Cu-67-SARTATE significantly extends survival in a hepatic model of neuroblastoma minimal residual disease. Jason Dearling, Ellen Van Dam, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7907331/

Detection and therapy of neuroblastoma minimal residual ... Treatment with [67Cu]Cu-SARTATE was more effective at 2 weeks post-tumor inoculation than at 4 weeks post-tumor inoculation in this model ...

5. northstarnm.com northstarnm.com/first-participant-treated-using-northstar-medical-radioisotopes-electron-accelerator/

NorthStar Medical Radioisotopes, LLC The CL04 trial (NCT04023331)1 is a theranostic trial evaluating 64Cu/67Cu SARTATE for diagnosis and treatment of high-risk neuroblastoma, an aggressive ...

6. claritypharmaceuticals.com claritypharmaceuticals.com/pipeline/sartate/

SARTATE - Next-Generation, Highly Targeted Copper- ... The trial data demonstrated 67Cu-SARTATE (SPECT/CT scan) was generally safe and well-tolerated in adult cancer patients. Clarity Pharmaceuticals.

7. urotoday.com urotoday.com/video-lectures/endourology-today/video/4232-copper-67-in-cancer-therapy-current-developments-and-future-potential-alan-taylor.html

Copper-67 (Cu-67 or 67Cu) in Cancer Therapy And we're seeing it with a safety profile, but you don't even see this safety profile in first-line therapies. So it represents, I think, a ...