Cellectar Biosciences, Inc., a biopharmaceutical company developing innovative agents for the detection and treatment of cancer, has enrolled first patient in its phase II imaging trial of I-124-CLR1404 in patients with glioblastoma.

Glioma, a type of tumour that starts in the brain and arises from glial cells, accounts for approximately 80 per cent of all primary malignant brain tumours. Glioblastoma, a type of glioma, is the most common adult primary brain cancer. The current standard imaging modality used to characterize malignant gliomas is magnetic resonance imaging (MRI). However, the true extent of tumor infiltration is often inadequately characterized prior to surgery and adjuvant radiation and chemotherapies. Further complicating effective clinical follow-up imaging of glioma patients is the incidence of pseudoprogression and radiation necrosis following treatment. Pseudoprogression and radiation necrosis can appear similar to recurrent glioblastoma on MRI. So a false positive finding that is misinterpreted as tumor recurrence may result in premature cessation of an effective therapy, and possibly subject patients to additional surgeries or treatments.

This phase II trial, being conducted at 10 NCI-designated cancer centres in the US, will compare the efficacy of I-124-CLR1404 positron emission tomography (PET) imaging in detecting glioblastoma with standard of care MRI based on pathology confirmation in approximately 36 patients.

“Developing new imaging agents that can reliably and selectively identify infiltrative tumor growth of malignant gliomas is an important priority for the neuro-oncology community,” commented John Kuo, MD, PhD, principal investigator of the I-124-CLR1404 phase II trial, associate professor of Neurological Surgery and Chair of the CNS Tumours group at the University of Wisconsin Carbone Cancer Centre. “Preclinical and pilot human studies of I-124-CLR1404 conducted under investigator-sponsored INDs have suggested remarkable specificity in malignant tumour and cancer stem cell uptake, and potential distinction between true tumour progression and pseudoprogression in patients with newly diagnosed or recurrent glioblastoma. Validating these initial findings in a clinical trial would represent a significant advance towards potential approval of I-124-CLR1404 for clinical use in the diagnosis and treatment of glioblastoma. I look forward to working with Cellectar and other investigators in this trial to more fully determine administration parameters and characterize the clinical benefits of I-124-CLR1404.”

The primary objective of this trial is to determine the optimal dose and imaging time points of I-124-CLR1404 in subjects with newly diagnosed or recurrent glioblastoma. The phase II trial is an open-label, multi-center study evaluating up to two doses (5 mCi and 7.5 mCi) of I-124-CLR1404 at multiple time points to determine the optimal parameters for PET/CT brain imaging.

A highly unique element of this clinical trial involves rigorous confirmation of imaging with pathology results. This permits exploratory analyses of the sensitivity and specificity of I-124-CLR1404 PET/CT compared to standard of care MRI. In addition, this will provide insights into the ability of I-124-CLR1404 PET to distinguish treatment-related effects such as pseudoprogression and radiation necrosis from true tumor recurrence.

I-124-CLR1404 pairs Cellectar’s proprietary phospholipid ether analog (PLE), acting as a cancer-targeted delivery and retention vehicle, with iodine-124, a well-established positron emission tomography (PET) imaging isotope with a radiation half-life of four days. In studies to date, I-124-CLR1404 selectively illuminated malignant tumors in over 60 animal models of different cancer types, demonstrating broad-spectrum, cancer-selective uptake and retention. Cellectar expects to complete a Phase II trial evaluating I-124-CLR1404 in glioblastoma in 2014. Additionally, multiple investigator sponsored Phase I/II clinical trials are ongoing across 11 solid tumor indications.