According to the last MD&A:
"Theralase®, subject to the required regulatory approvals, plans to intravenously inject Rutherrin® into patients via a Phase Ib/II adaptive clinical study design, to first determine localization to various cancer cells, including Glio Blastoma Multiforme (“GBM”) and Non-Small Cell Lung Cancer (“NSCLC”) and then in an adaptive design activate Rutherrin® with radiation with the intent of safely and effectively destroying the cancer of interest." Rutherrin can be delivered systemically and reach gbm tumours because it is one of only 2 photosensitizers that can cross the blood-brain barrier. The other photosensitizer that can do this is 5-ALA.
Researchers in Gernany are currently conducting a single site 30 patient Phase I/II dose escalation gbm radiodynamic study using orally administered 5-ALA
ALA-RDT in GBM: protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma Rutherrin will be delivered by injection and 5_ALA orally, but they will both be activated by ionizing radiation so the two trtials will be very comparable. Theralase has already done a pre-clinical study comparing Rutherrin and 5-ALA in the treatment of GBM and Rutherrin turned out to be much more effective. But the German researchers at the University Hospital of Mnster have already started their trial so they have a headstart. Despite Rutherrin's superiority over 5-ALA, it would certainly be in Theralase's best interest to start the GBM trial as soon as possible.
Efficacy of ruthenium coordination complex–based Rutherrin in a preclinical rat glioblastoma model Niklas Benedikt Pepper 1, Hans Theodor Eich 2, Michael Mther 3, Michael Oertel 2, Stephan Rehn 2, Dorothee Ccilia Spille 3, Walter Stummer 3
1 Department of Radiation Oncology, University Hospital of Mnster, Albert-Schweitzer-Campus 1, Building A1, 48149, Mnster, Germany. Niklas.pepper@ukmuenster.de.
2 Department of Radiation Oncology, University Hospital of Mnster, Albert-Schweitzer-Campus 1, Building A1, 48149, Mnster, Germany.
3 Department of Neurosurgery, University Hospital of Mnster, Albert-Schweitzer-Campus 1, Building A1, 48149, Mnster, Germany.
Free PMC article
Abstract
Background: Despite improvements in surgical as well as adjuvant therapies over the last decades, the prognosis for patients with glioblastoma remains poor. Five-Aminolevulinic acid (5-ALA) induced porphyrins are already used for fluorescence-guided resection and as photosensitizer for photodynamic therapy. New findings reveal their potential use as sensitizing agents in combination with ionizing radiation.
Methods: We initiated a phase I/II dose escalation study, treating patients with recurrence of glioblastoma with oral 5-ALA concurrent to radiotherapy (RT). This prospective single-center study based in the University Hospital Mnster aims to recruit 30 patients over 18 years of age with histologically verified recurrence of supratentorial glioblastoma in good performance status (KPS ≥ 60). Following a 3 + 3 dose-escalation design, patients having undergone re-resection will receive a 36 Gy RT including radiodynamic therapy fractions (RDT). RDT constitutes of oral administration of 5-ALA before the irradiation session. Two cohorts will additionally receive two fractions of neoadjuvant treatment three and two days before surgery. To determine the maximum tolerated dose of repeated 5-ALA-administration, the number of RDT-fractions will increase, starting with one to a maximum of eight fractions, while closely monitoring for safety and toxicity. Follow-up will be performed at two and five months after treatment. Primary endpoint will be the maximum tolerated dose (MTD) of repeated ALA-administration, secondary endpoints are event-free-, progression-free-, and overall-survival. Additionally, 5-ALA metabolites and radiobiological markers will be analysed throughout the course of therapy and tissue effects after neoadjuvant treatment will be determined in resected tissue. This protocol is in accordance with the SPIRIT guidelines for clinical trial protocols.
Discussion: This is the protocol of the ALA-RDT in GBM-study, the first-in-man evaluation of repeated administration of 5-ALA as a radiosensitizer for treatment of recurrent glioblastoma.
Trial registration: This study was approved by the local ethics committee of the Medical Association of Westphalia-Lippe and the University of Mnster on 12.10.2022, the German federal institute for Drugs and medical devices on 13.10.2022 and the federal office for radiation protection on 29.08.2022. This trial was registered on the public European EudraCT database (EudraCT-No.: 2021-004631-92) and is registered under www.cliniclatrials.gov (Identifier: NCT05590689).