Targeted Radiotherapy for Brain Tumor

Not currently recruiting at 7 trial locations

Overseen By Kate Oliver

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Cellectar Biosciences, Inc.

Must not be taking: Antitumor therapy

Disqualifiers: HIV, Serious infection, Cardiac dysfunction, 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: Unknown

Duration: 6-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CLR 131, a targeted radiotherapy, for children, teens, and young adults with difficult-to-treat or recurring brain tumors known as high-grade gliomas. The trial aims to determine the safety and effectiveness of CLR 131 at two different doses. Participants will receive the treatment in cycles to identify the most effective dose. Those diagnosed with high-grade glioma that does not respond to current treatments and have at least one measurable tumor may be suitable for this study. As a Phase 1 trial, participants will be among the first to receive CLR 131, aiding researchers in understanding how this new treatment works in people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antitumor or investigational therapy, you must wait for a certain period before joining the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that CLR 131 is likely to be safe for humans?

Research has shown that CLR 131 has been tested in children, teens, and young adults with difficult-to-treat brain tumors. The studies suggest that CLR 131 is generally well-tolerated. In earlier trials, patients received different doses, and the results showed some promise in managing the disease.

While specific safety data for CLR 131 in brain tumors is still being collected, it has been tested in other conditions, such as certain blood cancers. In these studies, CLR 131 was usually well-tolerated, but like any treatment, side effects may occur. Discussing potential risks and benefits with a doctor before joining a trial is important.

This trial is in its early stages, so researchers are still determining the best dose and assessing its safety. Participating in a trial like this could help improve understanding of CLR 131's safety and effectiveness in treating brain tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CLR 131 is unique because it offers a targeted radiotherapy approach specifically designed for tough-to-treat brain tumors like pediatric high-grade gliomas. Unlike traditional treatments such as surgery, chemotherapy, or general radiation therapy that can affect healthy brain tissue, CLR 131 delivers radiation directly to tumor cells using a phospholipid ether analog, minimizing damage to surrounding areas. This precision targeting not only holds promise for more effective treatment but also potentially reduces side effects, making it an exciting development in the fight against aggressive brain tumors.

What evidence suggests that CLR 131 might be an effective treatment for high-grade glioma?

Studies have shown that CLR 131 can help treat high-grade gliomas, aggressive brain tumors. Early results suggest it may extend the lives of children whose cancer has returned or resisted standard treatments. Research indicates that CLR 131 delivers targeted radiation directly to the tumor, helping to shrink it and slow the disease. Data from previous studies show promising signs of longer survival and better disease control in children with these challenging tumors. These encouraging results support further research into CLR 131's effectiveness. Participants in this trial will be divided into two dosing cohorts to explore different dosing regimens of CLR 131. ^{1 2 3 6 7}

Who Is on the Research Team?

Jarrod Longcor

Principal Investigator

Chief Operating Officer

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults aged 2-25 with high-grade glioma (a type of brain tumor) that has come back or hasn't responded to treatment. They must be in a stable condition, not pregnant, able to follow the study plan, and have certain blood counts and organ functions within specific ranges.

Inclusion Criteria

Estimated GFR > 60 ml/min/1.73m2 using the bedside Schwartz formula

I am between 10 and 25 years old.

Absolute neutrophil count ≥ 750/μL

Exclusion Criteria

I haven't had cancer treatment or experimental therapy recently.

Pregnancy or breast-feeding

I have HIV or a serious infection that is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CLR 131 in two dosing cohorts; first arm receives two doses of 20 mCi/m2 each, separated by 14 days for two cycles, with a third optional cycle. Second arm receives two doses of 10 mCi/m2 each, separated by 14 days for three cycles with a fourth optional cycle.

6-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression free survival and overall survival assessments.

3 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• CLR 131

Trial Overview

The trial is testing two different doses of CLR 131 to see how safe it is and if it works against relapsed or refractory high-grade gliomas in pediatric patients. It's a dose-finding study which means they're trying to find the right amount of drug that's effective but also safe.

How Is the Trial Designed?

Group I: Pediatric High-Grade Glioma Patients Experimental Treatment 1 Intervention

Two dosing cohorts will be explored; patients in the first arm will receive two doses, 20 mCi/m2 each, separated by 14 days for two cycles, with a third optional cycle. Patients in the second arm will receive two doses, 10 mCi/m2 each, separated by 14 days for three cycles with a fourth optional cycle.

CLR 131 is already approved in United States, European Union for the following indications:

Approved in United States as Iopofosine I-131 for:

• Relapsed or refractory multiple myeloma
• Lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia
• Diffuse large B-cell lymphoma

Approved in European Union as Iopofosine I-131 for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Cellectar Biosciences, Inc.

Lead Sponsor

Trials

15

Recruited

1,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a pilot trial involving 12 patients with brain tumors, 124I-CLR1404 showed significant uptake in 9 out of 13 tumors, particularly in high-grade tumors, indicating its potential as a selective imaging agent for cancer.

The study demonstrated high tumor-to-background ratios for malignant tumors at 24 and 48 hours post-injection, suggesting that 124I-CLR1404 could effectively differentiate between tumor and normal brain tissue, although further research is needed to confirm its clinical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors. Hall, LT., Titz, B., Robins, HI., et al.[2020]

In a study involving 27 adult patients with suspected high-grade brain tumors, [124I]CLR1404 PET/CT demonstrated high sensitivity for detecting tumor tissue, with positive uptake in nearly all patients diagnosed with primary or recurrent tumors.

The study found that [124I]CLR1404 PET/CT provided additional diagnostic information beyond standard MRI, as there was low concordance between PET uptake and MRI findings, indicating its potential to enhance clinical decision-making in brain tumor management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[124I]CLR1404 PET/CT in High-Grade Primary and Metastatic Brain Tumors. Hall, LT., Titz, B., Baidya, N., et al.[2021]

In a phase 1 study involving 8 patients with advanced solid tumors, a single injection of 370 MBq of (131)I-CLR1404 was well tolerated, with no severe adverse events reported, indicating a favorable safety profile.

The study suggests that (131)I-CLR1404 may be effective as an anti-cancer agent, with a predicted administered activity of approximately 740 MBq needed to deliver a therapeutic dose of 400 mSv to the bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety. Grudzinski, JJ., Titz, B., Kozak, K., et al.[2018]

The pilot study showed that CLR 124 PET imaging can effectively predict the dosimetry for CLR 131 therapy in a triple-negative breast cancer patient, indicating its potential for improving treatment planning.

Monte Carlo dosimetry methods, like RAPID, provided more accurate predictions of dose distribution compared to traditional methods, which is crucial for understanding how different doses affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretreatment CLR 124 Positron Emission Tomography Accurately Predicts CLR 131 Three-Dimensional Dosimetry in a Triple-Negative Breast Cancer Patient. Besemer, AE., Grudzinski, JJ., Weichert, JP., et al.[2020]

The study demonstrated that 131I-CLR1404, a tumor-targeted radiotherapeutic agent, effectively delayed tumor growth and improved survival in various pediatric cancer models, indicating its potential efficacy in treating pediatric malignancies.

CLR1404 showed selective uptake in pediatric cancer cells compared to normal cells, suggesting a favorable safety profile that minimizes damage to healthy tissue, which is crucial in treating young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Molecular Radiotherapy of Pediatric Solid Tumors Using a Radioiodinated Alkyl-Phospholipid Ether Analog. Baiu, DC., Marsh, IR., Boruch, AE., et al.[2019]

In a phase I clinical trial involving 15 patients, intraventricular iodine-131-labeled monoclonal antibody 3F8 (131I-3F8) was found to be generally well tolerated, with the maximum-tolerated dose identified as 10 mCi, while demonstrating a high CSF-to-blood ratio.

Three out of 13 assessable patients showed objective responses to the treatment, and no late toxicities were observed in two patients who remained in remission for over 3.5 years, suggesting potential clinical utility for targeting GD2 in CNS/LM malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. Kramer, K., Humm, JL., Souweidane, MM., et al.[2019]

Iodine-131 3F8, a monoclonal antibody targeting GD2-bearing tumors, was safely administered to 12 patients with brain tumors, showing effective localization in 9 out of 11 malignant gliomas and one metastatic melanoma without any side effects.

The best tumor delineation was observed with a 10 mCi dose, and the pharmacokinetics were consistent across different doses, indicating that this antibody can effectively target brain tumors with a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors. Arbit, E., Cheung, NK., Yeh, SD., et al.[2019]

The combination of interleukin-12 (IL-12) vaccine gene therapy and iodine-131 labeled monoclonal antibody LC-1 (RIT) significantly inhibited tumor growth in mice with Lewis lung carcinoma, showing a synergistic effect compared to either treatment alone.

Intratumoral injection of (131)I-LC-1 improved the delivery of the antibody to the tumor site, leading to increased tumor apoptosis and enhanced immune response, as indicated by up-regulated IL-12 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effects of 131I-LC-1 IgM and IL-12 vaccine on Lewis lung carcinoma. Yin, XL., Yan, X., Wen, M., et al.[2010]

The novel radiopharmaceutical CLR1404 (CLR 124) shows selective uptake and prolonged retention in pediatric solid tumors, indicating its potential effectiveness for treating conditions like neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma.

CLR 1404 demonstrated a 22% higher uptake compared to the standard treatment 124I-MIBG in neuroblastoma models, suggesting it could improve therapeutic outcomes and support the development of pediatric clinical trials for molecular radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacokinetics and Dosimetry Studies of 124I/131I-CLR1404 for Treatment of Pediatric Solid Tumors in Murine Xenograft Models. Marsh, IR., Grudzinski, J., Baiu, DC., et al.[2020]

Citations

1.

cellectar.com

cellectar.com/news-media/press-releases/detail/379/cellectar-biosciences-receives-rare-pediatric-disease

Press Releases

CLOVER-2 Phase 1 Clinical Study Evaluating Iopofosine I 131 in Relapsed/Refractory Pediatric High-Grade Glioma Patients Showed Extended ...

2.

cancernetwork.com

cancernetwork.com/view/iopofosine-i-131-shows-preliminary-survival-benefit-in-pediatric-r-r-glioma

Iopofosine I 131 Shows Preliminary Survival Benefit in ...

Treatment with iopofosine I 131 demonstrated early survival benefit in a small cohort of pediatric patients with relapsed/refractory high-grade gliomas.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03478462

NCT03478462 | Dose Escalation Study of CLR 131 in ...

Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

4.

finance.yahoo.com

finance.yahoo.com/news/cellectar-biosciences-receives-rare-pediatric-123000510.html

Cellectar Biosciences Receives Rare Pediatric Disease ...

CLOVER-2 Phase 1 Clinical Study Evaluating Iopofosine I 131 in Relapsed/Refractory Pediatric High-Grade Glioma Patients Showed Extended ...

5.

cellectar.com

cellectar.com/news-media/press-releases/detail/375/cellectar-biosciences-presented-compelling-data-in-oral

Press Releases

“The data from our CLOVER-2 study demonstrate encouraging signs of tumor volume reduction, disease control and extended survival in children and ...

6.

cellectar.com

cellectar.com/news-media/press-releases/detail/361/cellectar-biosciences-provides-update-on-clover-2-phase-1

Press Releases

All patients receiving a minimum of 55 mCi total administered dose (n=7) experienced an average of 5.4 months of PFS and 8.6 months of OS, ongoing.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02952508

NCT02952508 | Study of Iopofosine I 131 (CLR ...

This study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL) ...