Abstract: SAT 172
First Clinical Application of the Labelled Gastrin Analogue CP04 - a Novel CCK2/Gastrin Receptor-Localizing Peptide Probe for Personalized Diagnostics and Therapy of Patients with Progressive or Metastatic Medullary Thyroid Carcinoma. Phase I Study Gran-T-MTC
Presenter: Alicja Hubalewska-D
Although many drugs are under investigation or even tested in a clinical context, there is still no universally recommended treatment regimen for advanced MTC. view more
Although many drugs are under investigation or even tested in a clinical context, there is still no universally recommended treatment regimen for advanced MTC.
The ultimate goal of the project conducted within the international collaboration, is to establish the safety of the iv. administration of the therapeutic amount of the gastrin analogue CP04 and to assess the biodistribution and dosimetry of 111In-CP04 in MTC and normal tissues. The scientific justification for choosing the proposed gastrin analogue (DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04) as a candidate for innovative therapy are: very high CCK-2 receptor expression in MTC and the best pharmacokinetics properties of the numerous gastrin analogues tested.
At present the preclinical part of the study has been finalized. The positive results of the preclinical part of the presented study confirmed the possibility of applying 111In-CP04 in the clinical part of the trial.
Material and methods: 25 patients with progressive/metastatic inoperable and histologically proven MTC with positive 18F-FDG PET-CT/CT/MRI or elevated calcitonin doubling time (Ct DT ) are being enrolled in the study.
Study Design: The first 4 patients will receive 2 different doses of CP04: low-dose (diagnostic - 10 µg) and high-dose (therapeutic - 50 µg) of 111In-CP04. If no serious adverse events (SAE) are observed, the remaining patients will be randomized in 2 arms: high-dose of 111In-CP04 with and without Gelofusine infusion (to decrease kidneys uptake). Safety of 111In-CP04 intravenous administration, tracer biodistribution, pharmacokinetics, and diagnostic sensitivity/specificity will be assessed.
Initial results: 3 out of 4 patients (3 women aged 55, 58 and 29 years) planned to receive 10 ug dose of CP04 were examined (basal Ct: 279.0, 824.0, 563.0 pg/ml; normal range: 0.0-10.0). In all patients no adverse events were observed. In 2 patients typical foci of pathological tracer uptake in the cervical metastatic lymph nodes were detected and in one of them the MTC infiltration around the tracheostomy tube was found. In the 3rd woman with negative FDG-PET/CT and high level of serum calcitonin the small foci of tracer uptake in the cervical region were detected for further evaluation.
At this stage of the Gran-T-MTC Study, the promising properties of the new gastrin analogue in identifying MTC tissues warrant further studies on the compound. It is worth stressing that maybe it is the first step in the development of a more efficient therapeutic strategy against this challenging neoplasm.