Targeted Radiotherapy for Brain Tumor
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Cellectar Biosciences, Inc.
No Placebo Group
Approved in 2 jurisdictions
Trial Summary
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).
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.
35679What 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.
45679Do 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 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.
12578Eligibility 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.Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Pediatric High-Grade Glioma PatientsExperimental Treatment1 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
UT Southwestern Medical CenterDallas, TX
Hospital for Sick ChildrenToronto, Canada
Stanford UniversityPalo Alto, CA
Cincinnati Children's Hospital Medical CenterCincinnati, OH
More Trial Locations
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Who is running the clinical trial?
Cellectar Biosciences, Inc.Lead Sponsor
National Cancer Institute (NCI)Collaborator
References
Quantitative studies of monoclonal antibody targeting to disialoganglioside GD2 in human brain tumors. [2019]Iodine-131 3F8, a murine IgG3 monoclonal antibody that targets to GD2-bearing tumors, was administered intravenously to 12 patients with brain tumors. Six patients received 2 mCi (0.74 Bq) of 131I-3F8, five patients 10 mCi (3.7 Bq)/1.73 m2 of 131I-3F8, and one patient 2.6 mCi (0.96 Bq) of 124I-3F8, with no side-effects. Nine of 11 malignant gliomas and the single metastatic melanoma showed antibody localization, with the best tumor delineation on single-photon emission tomography (SPET) following 10 mCi (3.7 Bq)/1.73 m2 dose. No nonspecific uptake in the normal craniospinal axis was detected. There was no difference in the pharmacokinetics of low-dose versus the higher-dose antibody groups; plasma and total-body half-lives were 18 h and 49 h, respectively. Surgical sampling and time-activity curves based on quantitative imaging showed peak uptake in high-grade glioma at 39 h, with a half-life of 62 h. Tumor uptake at time of surgery averaged 3.5 x 10(-3) %ID/g and peak activity by the conjugate view method averaged 9.2 x 10(-3) %ID/g (3.5-17.8). Mean radiation absorption dose was 3.9 rad per mCi injected (range 0.7-9.6) or 10.5 cGy/Bq (range 1.9-26). There was agreement on positive sites when immunoscintigraphy was compared with technetium-99m glucoheptonate/diethylene triamine penta-acetic acid planar imaging, thallium-201 SPET, and fluorine-18 fluorodeoxyglucose positron emission tomography. Taken together, these data suggest that quantitative estimates of antibody targeting to intracranial tumors can be made using the modified conjugate view method.
Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. [2019]Tumors metastasizing to the CNS and leptomeninges (LM) are associated with significant mortality. We tested the toxicity, pharmacokinetics, and dosimetry of intraventricular iodine-131-labeled monoclonal antibody 3F8 (131I-3F8) targeting GD2-positive CNS/LM disease in a phase I clinical trial.
Synergistic antitumor effects of 131I-LC-1 IgM and IL-12 vaccine on Lewis lung carcinoma. [2010]This study was designed to determine the antitumor effects of iodine-131 labeled monoclonal antibody LC-1 ((131)I-LC-1), interleukin-12 (IL-12) vaccine, or the combination of both on C57BL/6 mice bearing Lewis lung carcinoma (LLC) tumors. Tumor-bearing mice models were randomly divided into 4 groups that were respectively injected intratumorally with phosphate buffered solution (PBS), IL-12 vaccine gene therapy (GT), (131)I-LC-1 radioimmuno-therapy (RIT), or GT+RIT. Tumor volumes were measured before and after treatment. ELISA and RT-PCR determined the expression of IL-l2. LC-1 monoclonal antibody (Mab) was labeled with Na(131)I. Cytolytic T lymphocyte (CTL) activity assay, Natural Killer cell (NK) activity assay and apoptosis analysis were performed. Intratumoral (131)I-LC-1 injection leads to higher delivery of the antibody to the tumor. Tumor apoptosis occurred in the GT, RIT and GT+RIT groups. Tumor growth was inhibited in the GT, RIT and GT+RIT groups. Compared with other groups, the combination of GT+RIT up-regulated the expression of IL-l2 gene and inhibited the tumor growth more effectively than either GT or RIT alone (p
A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety. [2018](131)I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of (131)I-CLR1404.
Targeted Molecular Radiotherapy of Pediatric Solid Tumors Using a Radioiodinated Alkyl-Phospholipid Ether Analog. [2019]External-beam radiotherapy plays a critical role in the treatment of most pediatric solid tumors. Particularly in children, achieving an optimal therapeutic index to avoid damage to normal tissue is extremely important. Consequently, in metastatic disease, the utility of external-beam radiotherapy is limited. Molecular radiotherapy with tumor-targeted radionuclides may overcome some of these challenges, but to date there exists no single cancer-selective agent capable of treating various pediatric malignancies independently of their histopathologic origin. We tested the therapeutic potential of the clinical-grade alkyl-phospholipid ether analog CLR1404, 18-(p-iodophenyl)octadecyl phosphocholine, as a scaffold for tumor-targeted radiotherapy of pediatric malignancies. Methods: Uptake of CLR1404 by pediatric solid tumor cells was tested in vitro by flow cytometry and in vivo by PET/CT imaging and dosimetry. The therapeutic potential of 131I-CLR1404 was evaluated in xenograft models. Results: In vitro, fluorescent CLR1404-BODIPY showed significant selective uptake in a variety of pediatric cancer lines compared with normal controls. In vivo tumor-targeted uptake in mouse xenograft models using 124I-CLR1404 was confirmed by imaging. Single-dose intravenous injection of 131I-CLR1404 significantly delayed tumor growth in all rodent pediatric xenograft models and extended animal survival while demonstrating a favorable side effect profile. Conclusion:131I-CLR1404 has the potential to become a tumor-targeted radiotherapeutic drug with broad applicability in pediatric oncology. Because 131I-CLR1404 has entered clinical trials in adults, our data warrant the development of pediatric clinical trials for this particularly vulnerable patient population.
PET/CT imaging of the diapeutic alkylphosphocholine analog 124I-CLR1404 in high and low-grade brain tumors. [2020]CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with 124I for PET imaging, 131I for targeted radiotherapy and/or SPECT imaging, or 125I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of 124I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of 124I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. 124I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of 124I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. 124I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. 124I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has potential clinical relevance. Expansion of these studies is required to determine the clinical significance of the 124I-CLR1404 PET findings.
Pretreatment CLR 124 Positron Emission Tomography Accurately Predicts CLR 131 Three-Dimensional Dosimetry in a Triple-Negative Breast Cancer Patient. [2020]Label="INTRODUCTION" NlmCategory="BACKGROUND">CLR1404 is a theranostic molecular agent that can be radiolabeled with 124I (CLR 124) for positron emission tomography (PET) imaging, or 131I (CLR 131) for single-photon emission computed tomography (SPECT) imaging and targeted radionuclide therapy. This pilot study evaluated a pretreatment dosimetry methodology in a triple-negative breast cancer patient who was uniquely enrolled in both a CLR 124 PET imaging clinical trial and a CLR 131 therapeutic dose escalation clinical trial.
Preclinical Pharmacokinetics and Dosimetry Studies of 124I/131I-CLR1404 for Treatment of Pediatric Solid Tumors in Murine Xenograft Models. [2020]Cancer is the second leading cause of death for children between the ages of 5 and 14 y. For children diagnosed with metastatic or recurrent solid tumors, for which the utility of external-beam radiotherapy is limited, the prognosis is particularly poor. The availability of tumor-targeting radiopharmaceuticals for molecular radiotherapy (MRT) has demonstrated improved outcomes in these patient populations, but options are nonexistent or limited for most pediatric solid tumors. 18-(p-iodophenyl)octadecylphosphocholine (CLR1404) is a novel antitumor alkyl phospholipid ether analog that broadly targets cancer cells. In this study, we evaluated the in vivo pharmacokinetics of 124I-CLR1404 (CLR 124) and estimated theranostic dosimetry for 131I-CLR1404 (CLR 131) MRT in murine xenograft models of the pediatric solid tumors neuroblastoma, rhabdomyosarcoma, and Ewing sarcoma. Methods: Tumor-bearing mice were imaged with small-animal PET/CT to evaluate the whole-body distribution of CLR 124 and, correcting for differences in radioactive decay, predict that of CLR 131. Image volumes representing CLR 131 provided input for Geant4 Monte Carlo simulations to calculate subject-specific tumor dosimetry for CLR 131 MRT. Pharmacokinetics for CLR 131 were extrapolated to adult and pediatric humans to estimate normal-tissue dosimetry. In neuroblastoma, a direct comparison of CLR 124 with 124I-metaiodobenzylguanidine (124I-MIBG) in an MIBG-avid model was performed. Results: In vivo pharmacokinetics of CLR 124 showed selective uptake and prolonged retention across all pediatric solid tumor models investigated. Subject-specific tumor dosimetry for CLR 131 MRT presents a correlative relationship with tumor-growth delay after CLR 131 MRT. Peak uptake of CLR 124 was, on average, 22% higher than that of 124I-MIBG in an MIBG-avid neuroblastoma model. Conclusion: CLR1404 is a suitable theranostic scaffold for dosimetry and therapy with potentially broad applicability in pediatric oncology. Given the ongoing clinical trials for CLR 131 in adults, these data support the development of pediatric clinical trials and provide detailed dosimetry that may lead to improved MRT treatment planning.
[124I]CLR1404 PET/CT in High-Grade Primary and Metastatic Brain Tumors. [2021]Label="PURPOSE">There is a continuous search for imaging techniques with high sensitivity and specificity for brain tumors. Positron emission tomography (PET) imaging has shown promise, though many PET agents either have a low tumor specificity or impractical physical half-lives. [124I]CLR1404 is a small molecule alkylphosphocholine analogue that is thought to bind to plasma membrane lipid rafts and has shown high tumor-to-background ratios (TBR) in a previous pilot study in brain tumor patients. This study attempts to define the clinical value of [124I]CLR1404 PET/CT (aka CLR124).