Targeted Radiotherapy for Brain Tumor

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

50 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment CLR 131 for brain tumors?

Research shows that CLR1404, a component of CLR 131, is taken up by brain tumors and retained well, which suggests it could be effective in targeting these tumors. Additionally, in pediatric cancer models, CLR1404 delayed tumor growth and extended survival, indicating its potential as a targeted treatment. ^{1 2 3 4 5}

Is CLR 131 safe for use in humans?

CLR 131, also known as Iopofosine I-131, has been tested in clinical trials and preclinical studies, showing a favorable safety profile with selective uptake in tumors and minimal side effects in animal models. It has been used in adults and is being considered for pediatric trials, indicating its potential safety across different age groups. ^{2 5 6 7 8}

What makes the drug CLR 131 unique for treating brain tumors?

CLR 131 is unique because it is a targeted radiotherapy that selectively accumulates in tumor cells, minimizing damage to normal brain tissue. It uses a radioactive isotope, I-131, to deliver radiation directly to the tumor, which can help delay tumor growth and extend survival with fewer side effects compared to traditional radiotherapy. ^{1 2 4 5 9}

What is the purpose of this trial?

The purpose of this dose finding study is to evaluate the safety and efficacy of 2 different dose levels of CLR 131 in children, adolescents and young adults with relapsed or refractory high-grade glioma (HGG).

Research Team

Jarrod Longcor

Principal Investigator

Chief Operating Officer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Targeted Molecular Radiotherapy of Pediatric Solid Tumors Using a Radioiodinated Alkyl-Phospholipid Ether Analog. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effects of 131I-LC-1 IgM and IL-12 vaccine on Lewis lung carcinoma. [2010]

4. United States pubmed.ncbi.nlm.nih.gov

[124I]CLR1404 PET/CT in High-Grade Primary and Metastatic Brain Tumors. [2021]

5. United States 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. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacokinetics and Dosimetry Studies of 124I/131I-CLR1404 for Treatment of Pediatric Solid Tumors in Murine Xenograft Models. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors. [2019]

9. United States 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. [2018]