MITIGATE-NeoBOM: A Study to Evaluate 68Ga- NeoBOMB1 in Patients With Advanced TKI-treated GIST Using PET/CT

Gastrointestinal Stromal Tumors Clinical Trial

Official title: MITIGATE-NeoBOMB1: A Phase I/IIa Study to Evaluate Safety, Biodistribution, Dosimetry+Preliminary Diagnostic Performance of 68Ga-NeoBOMB1 in Pat. With Advanced TKI-treated GIST Using Positron-emission Tomography/Computer Tomography (PET/CT)

Status Completed

Clinical Trial Summary

Tyrosine-kinase Inhibitors (TKI) resistance in gastrointestinal stromal tumours (GIST) is a common problem after prolonged treatment periods. The main objectives of this monocentric diagnostic Phase I/IIa study are safety and tolerability, pharmacokinetics and dosimetry of 68Ga-NeoBomb1 in GIST patients. The rationale behind this study is to improve diagnostic accuracy in GIST via positron-emission tomography/computer tomography (PET-CT) with a focus on TKI-resistant subtypes. Better detection, classification and definition of lesion extent are expected from the use of 68Ga-NeoBOMB1.

Clinical Trial Description

Rationale of the design:

This is a monocentric diagnostic Phase I/IIa study. Due to the very limited number of patients and the rare nature of the disease the study was designed as a combination of phases I and IIa.

The main objectives of such an early phase clinical trial are safety and tolerability, pharmacokinetics and (in the case of radiopharmaceuticals) dosimetry aspects. For the first 6 patients, the focus of the study will be on safety, tolerability and pharmacokinetics. Therefore, both TKI-resistant and TKI-sensitive GIST patients will be included. As resistant patients are typically in 2nd- or 3rd-line TKI treatment prone to substantial side effects and potentially suffer from a greater extent of disease, the study design includes a limited number of non-resistant GIST patients to address a possible bias regarding tolerability and side effects profile of 68Ga-NeoBOMB1.

After 6 included patients an interim analysis of safety and pharmacokinetic data including PBPK modelling and dosimetry calculation will be performed. Thereby it will be decided, whether the data generation is sufficient for a final calculation of dosimetry, if so pharmacological and dosimetric aspects can be omitted in the last 6 patients, reducing the burden for these patients considerably (less number of scans, no blood and urine sampling). This analysis will also reveal the optimal time window for PET/CT imaging.

After the establishment of these baseline findings, the second part of the study will emphasize the assessment of imaging data towards targeting properties of the GRP(gastrin releasing peptide)-receptor-specific radiopharmaceutical 68Ga-NeoBOMB1 as proof of the molecular imaging principle. In this phase only patients with confirmed GRPR receptor expression via Immunohistochemistry will be included. Nonetheless, safety and tolerability still remain a primary objectives in this part of the study.

As there are no preclinical indications that the GRP receptor status of TKI resistance is variable, all objectives should be met including targeting properties of 68Ga-NeoBOMB1 also in non-resistant patients. Nonetheless, changes in GRP-receptor expression under treatment pressure may still exist. Therefore in both phases a minimum of 50% of the patients have to show resistance to TKI treatment, where therapeutic option are extremely limited. This will allow providing data in patients that will most likely benefit most from an improved target characterisation and GRPR targeting therapy approaches.

Study conduct:

Within 28 days after the patient's positive evaluation and written informed consent, the imaging study will be performed. During the study, patients will be shortly hospitalised. These pre-planned hospitalisations for study purposes will not be considered as (serious) adverse events. The radiopharmaceutical will be administered to the patient directly at the imaging system (PET-CT).

In the first phase of the trial including the first six patients a series of dynamic scans between 0 and 45 min and static whole-body PET images at 1, 2 and 3-4h will be obtained to determine pharmacokinetics and absorbed doses to normal organs and to tumorous lesions. Blood samples drawn concomitantly at the time of imaging will be collected to estimate residence times in blood and to derive the bone marrow absorbed dose (max. 10 samples during the hospitalisation). Urine will be collected to determine the bladder wall and kidney absorbed doses. Regions of interest for critical organs and tumour lesions will be drawn using the acquired images resulting in time-activity curves with quantitative fractions of administered activity. Residence times of radioactivity from this analysis will be calculated. All dosimetric calculations will be performed by feeding the residence times as well as blood and urine activities into an appropriate software program (OLINDA/EXAM).

The second phase is in principle conducted in the same way, if interim analysis returns sufficient data for dosimetry and pharmacokinetics, PET images will be reduced to 2 whole body scans within the optimal time window and blood and urine sampling can be omitted. ;

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

• NCT number: NCT02931929
• Study type: Interventional
• Source: Medical University Innsbruck
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 28, 2016
• Completion date: April 9, 2019