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

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ClinicalTrials.gov Identifier: NCT02931929
Recruitment Status : Completed
First Posted : October 13, 2016
Last Update Posted : July 19, 2019
Sponsor:
Collaborator:
European Union
Information provided by (Responsible Party):
Irene Virgolini, Medical University Innsbruck

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.

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: 68Ga-NeoBOMB1, 2-vial kit Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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)
Actual Study Start Date : November 28, 2016
Actual Primary Completion Date : April 9, 2019
Actual Study Completion Date : April 9, 2019


Arm Intervention/treatment
68Ga-NeoBOMB1
68Ga-NeoBOMB1, 2-vial kit for radiolabelling. I.v. Administration after radiolabelling
Drug: 68Ga-NeoBOMB1, 2-vial kit
intravenous application of a radiopharmaceutical for Positron Emission tomography (PET)
Other Name: NeoBOMB1




Primary Outcome Measures :
  1. Safety and tolerability: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: day 12-20 after administration ]
    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.

  2. Organ and compartment dosimetry data, human pharmacokinetics of 68Ga-NeoBOMB1 and identification of potentially dose-limiting organs [ Time Frame: 3-4 hours after administration ]

    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. Preliminary targeting properties of 68Ga-NeoBOMB1 in advanced, GRP positive GIST tumours as assessed by SUV [ Time Frame: 3-4 hours after administration ]
    GIST lesion tracer accumulation will be assessed visually and measured as relative signal intensity (compared to blood pool activity, SUV) for known lesions.


Secondary Outcome Measures :
  1. Targeting properties in comparison with standard imaging modalities such as FDG-PET or MRI as assessed by sensitivity and specificity [ Time Frame: 3-4 hours after administration ]
    The lesion demarcation from 68Ga-NeoBOMB1-PET will be compared to contrast-enhanced computed tomography and FDG-PET (if available).

  2. 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 [ Time Frame: 3-4 hours after administration ]
    Relative lesion growth tendency (as calculated from comparing current and previous CT scans) will be correlated to their respective tracer uptake (SUV).

  3. Identification of target tissue and improved target volume definition for potential locoregional treatment (RFA or external beam) [ Time Frame: 3-4 hours after administration ]

    A comparison will be made whether 68Ga-NeoBOMB1-PET could offer additional information for a potential local therapy such as radiofrequency ablation (RFA) or external beam radiation as determined by definition of lesion amount and extent.

    Therapeutic interventions will not be part of the current study


  4. To extrapolate absorbed tumour doses for potential application of 177Lu NeoBOMB1 (in first 6 patients) [ Time Frame: 3-4 hours after administration ]
    Estimation of tumour and organ/compartment doses will be performed by means of a physiology-based pharmacokinetic modelling to assess the potential feasibility of a therapeutic approach of 177Lu-NeoBOMB1



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02931929


Locations
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Austria
Medical University Innsbruck
Innsbruck, Tirol, Austria, 6020
Sponsors and Collaborators
Medical University Innsbruck
European Union
Investigators
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Principal Investigator: Irene Virgolini, Univ-Prof.Dr Head of department of nuclear medicine

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Responsible Party: Irene Virgolini, Univ.-Prof. Dr. med., Medical University Innsbruck
ClinicalTrials.gov Identifier: NCT02931929     History of Changes
Other Study ID Numbers: MITIGATE-NeoBOMB1
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases