Gastrointestinal stromal tumours previously or currently under TKI-treatment including at least 50% TKI-resistant patients
Conditions
Interventions
Product Name: Kit for the preparation of 68Ga-NeoBOMB1
Product Code: NeoBOMB1
Pharmaceutical Form: Kit for radiopharmaceutical preparation
Sponsors
Medical University Innsbruck
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Understanding and provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures • Patients with histologically confirmed advanced GIST • Previous or current TKI treatment • A minimum of 50% of patients showing either 1st-, 2nd- or 3rd-line TKI-resistance documented either through RECIST 1.1 criteria, Choi-criteria or FDG-CT/PET and showing presence of at least one surgically untreatable primary or metastasis confirmed with either 18F-FDG PET/CT or structural imaging (CT, MRI) and a minimum of 25% non-resistant patients. • Karnofsky performance status > 70% • Age > 21 years. • Participating men must use a single barrier method for contraception for 1 month after completion of the trial starting at the day of application of 68Ga-NeoBOMB1. • Women of childbearing age must use two highly effective methods of contraception during the trial and 6 months after its completion if not in menopause (defined as onset of menopause without menstruation for over 1 year) or after hysterectomy. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective: o Oral hormonal contraception (‘pill’) (as far as its efficacy is not expected to be impaired during the trial, e.g. with IMPs that cause vomiting and diarrhoea, adequate safety cannot be assumed) o Dermal hormonal contraception o Vaginal hormonal contraception (NuvaRing®) o Contraceptive plaster o Long-acting injectable contraceptives o Implants that release progesterone (Implanon®) o Tubal ligation (female sterilisation) o Intrauterine devices that release hormones (hormone spiral) o Double barrier methods o This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus). o The regulations for contraception are derived from Guideline ICH E8 Chapter 3.2.2.1 Selection of subjects together with ICH M3 Note 4 • Confirmed GRPR expression (phase II only) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: • Renal insufficiency with an eGFR 2) • Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and without evidence of recurrence for 5 years • Participation in any other investigational trial within 30 days of study entry with potential interactions regarding the study drugs or the underlying disease • Pregnancy, breast-feeding • Patients with concurrent illnesses that might preclude study completion or interfere with study results • Patients with bladder outflow obstruction or unmanageable urinary incontinence • Known or expected hypersensitivity to 68Gallium, Bombesin or to any of the excipients of NeoBOMB1. • Any condition that precludes raised arms position for prolonged imaging purposes. • Prior administration of a radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used on such radiopharmaceutical. • History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study. • Clinically significant illness or clinically relevant trauma within 2 weeks before the administration of the investigational product. • Subjects with any kind of dependency on the investigator or is employed by the sponsor or investigator • Subjects held in an institution by legal or official order
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: end of the study; Main Objective: Phase I part: • Safety, tolerability • Human pharmacokinetics and dosimetry data to determine the organ doses and to identify potentially dose-limiting critical organs through PBPK modelling Phase I/IIa part: • Safety, tolerability • Preliminary targeting properties of 68Ga-NeoBOMB1 in advanced, GRP positive GIST tumours. ; Secondary Objective: • Targeting properties in comparison with standard imaging modalities such as FDG-PET or MRI • Qualitative comparison of targeting properties of 68Ga-NeoBOMB1 in resistant vs non-resistant tumour lesions in patients undergoing TKI treatment • Identification of target tissue and improved target volume definition for potential locoregional treatment (RFA or external beam) • To extrapolate absorbed tumour doses for potential application of 177Lu NeoBOMB1 (in the first 6 patients) ; Primary end point(s): Safety & Tolerability • Tolerability and safety of the administration of 68Ga-NeoBOMB1 in a diagnostic dose • Last follow-up visit (visit 3) for previous participant in first 3 participants Human Pharmacokinetics • Generation of decay corrected time activity curves from 68Ga-NeoBOMB1 PET/CT images in normal organs, tumour lesions. • Quantification of urinary excretion of 68Ga-NeoBOMB1 • Calculation of half-life of 68Ga-NeoBOMB1 in blood Dosimetry • Generation of non-decay-corrected time activity curves and residence times from 68Ga-NeoBOMB1 PET/CT images in normal organs, tumour lesions • Calculation of absorbed doses and effective whole body dose of 68Ga-NeoBOMB1, also by PBPK modelling of 68Ga-NeoBOMB1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Number of tumour lesion detected by 68Ga-NeoBOMB1 in comparison with standard imaging modalities such as FDG-PET or MRI and comparison of resistant vs non-resistant patients • Target identification and volume definition based on 68Ga-NeoBOMB1 images for potential locoregional treatment (RFA or external beam) • Absorbed tumour doses of 177Lu NeoBOMB1 extrapolated from 68Ga-dosimetric data and definition of dose limiting organ for radionuclide therapy ;Timepoint(s) of evaluation of this end point: end of the study | — |
Countries
Austria
Contacts
Public ContactDepartment of nuclear medicine
Medical University Innsbruck
Outcome results
None listed