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

• Status: Completed
• Trial end date: 2019-04-09
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical University Innsbruck
• Collaborator: European Union

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:

• 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)

• Dermal hormonal contraception

• Vaginal hormonal contraception (NuvaRing®)

• Contraceptive plaster

• Long-acting injectable contraceptives

• Implants that release progesterone (Implanon®)

• Tubal ligation (female sterilisation)

• Intrauterine devices that release hormones (hormone spiral)

• Double barrier methods

• 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).

• 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 in tumour lesion(s) by immunohistochemistry or PCR (phase IIa only)

Exclusion Criteria:

• Renal insufficiency with an eGFR < 45 ml/min/1.72m2 or intolerance to any constituents of intravenous CT-contrast agents, preventing their administration (in cases without an available recent and sufficient contrast-enhanced CT examination)

• Higher than grade 2 hematotoxicity (CTC > 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 employed by the sponsor or investigator

• Subjects held in an institution by legal or official order