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

NCT02931929 | Completed Phase 1

• 1 other identifier: MITIGATE-NeoBOMB1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastrointestinal Stromal Tumors

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  Patients will undergo physical examinations, ECG, blood pressure measurements as well as analysis of blood biochemistry (haemoglobin, haematocrit, RBC count, WBC count, absolute neutrophil count, differential WBC count (neutrophils, eosinophils, basophils, lymphocytes, monocytes \[%\]), platelets), haematology (glucose, urea, creatinine, eGFR (calculated), bilirubin, Na, K, Cl, Ca, GOT \[ASAT\], GPT \[ALAT\], γGT, pancreas lipase and amylase, ALP, LDH, CK, CRP, serum albumin), coagulation parameters (Quick, INR, aPTT, fibrinogen) and semi-quantitative urine analysis (leukocytes, nitrite, erythrocytes, pH, protein). These measurements and assessments will be repeated during and after the application of 68Ga-NeoBOMB1. Prior to the study inclusion, prior to application of 68Ga-NeoBOMB1 and during the second follow-up a potential pregnancy will be assessed. The presence and severity of adverse events will be judged and reported according to CTCAE v4.03.

  day 12-20 after administration

• Organ and compartment dosimetry data, human pharmacokinetics of 68Ga-NeoBOMB1 and identification of potentially dose-limiting organs

  Pharmacokinetic data will be acquired by measuring 68Ga-NeoBOMB1 distribution over time through successive dynamic/semi-dynamic/static PET scans. Time activity curves will be generated to determine relative distribution among and doses for all relevant organs and compartments \[% of injected radioactivity in MBq\] through a physiology-based pharmacokinetic modelling approach (OLINDA/EXAM). To gather more information, successive blood and urine sampling will also be used to provide blood activity and excretion information and estimate bloodpool/bone marrow doses.

  3-4 hours after administration

• Preliminary targeting properties of 68Ga-NeoBOMB1 in advanced, GRP positive GIST tumours as assessed by SUV

  GIST lesion tracer accumulation will be assessed visually and measured as relative signal intensity (compared to blood pool activity, SUV) for known lesions.

  3-4 hours after administration

Secondary Outcomes (4)

• Targeting properties in comparison with standard imaging modalities such as FDG-PET or MRI as assessed by sensitivity and specificity

  3-4 hours after administration

• Qualitative comparison of targeting properties of 68Ga-NeoBOMB1 in resistant vs non-resistant tumour lesions in patients undergoing TKI Treatment as assessed by presence of tracer uptake and SUV

  3-4 hours after administration

• Identification of target tissue and improved target volume definition for potential locoregional treatment (RFA or external beam)

  3-4 hours after administration

• To extrapolate absorbed tumour doses for potential application of 177Lu NeoBOMB1 (in first 6 patients)

  3-4 hours after administration

Study Arms (1)

68Ga-NeoBOMB1

OTHER

68Ga-NeoBOMB1, 2-vial kit for radiolabelling. I.v. Administration after radiolabelling

Drug: 68Ga-NeoBOMB1, 2-vial kit

Interventions

68Ga-NeoBOMB1, 2-vial kit DRUG

intravenous application of a radiopharmaceutical for Positron Emission tomography (PET)

Also known as: NeoBOMB1

68Ga-NeoBOMB1

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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®)

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University Innsbruck: lead
• European Union: collaborator

Study Sites (1)

Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Irene Virgolini, Univ-Prof.Dr

  Head of department of nuclear medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.-Prof. Dr. med.

Study Record Dates

• First Submitted: September 29, 2016
• First Posted: October 13, 2016
• Study Start: November 28, 2016
• Primary Completion: April 9, 2019
• Study Completion: April 9, 2019
• Last Updated: July 19, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)