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[68Ga]-NeoBOMB1 Imaging in Patients With Malignancies Known to Overexpress Gastrin Releasing Peptide Receptor (GRPR) (NeoFIND)

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ClinicalTrials.gov Identifier: NCT03724253
Recruitment Status : Terminated (Recruitment was stopped before the target sample size was achieved.)
First Posted : October 30, 2018
Last Update Posted : June 12, 2020
Sponsor:
Information provided by (Responsible Party):
Advanced Accelerator Applications

Brief Summary:
This was a Phase II, multi-center, open label, single dose study in patients with tumor types known to overexpress Gastrin-Releasing Peptide Receptor (GRPR), including breast, prostate, colorectal, Non-Small Cell Lung Cancer (NSCLC) and Small-Cell Lung Cancer (SCLC).

Condition or disease Intervention/treatment Phase
Breast Cancer Prostate Cancer Colorectal Cancer Non Small Cell Lung Cancer Small Cell Lung Cancer Drug: [68Ga]-NeoBOMB1 Phase 2

Detailed Description:
A total of 50 subjects were planned for the study (10 subjects for the dosimetry group and 40 subjects for the non dosimetry group). The sponsor decided to close the recruitment prematurely, leading to a low sample size. In total, 22 subjects were screened for eligibility and 19 subjects were enrolled (2 subjects in the dosimetry group and 17 subjects in the non dosimetry group).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study design included a dosimetry and non-dosimetry groups and with the following tumor types:

  • Breast Cancer: dosimetry and non-dosimetry groups
  • Prostate Cancer: dosimetry and non-dosimetry groups
  • Colorectal cancer: non-dosimetry group
  • Non-Small Cell Lung Cancer (NSCLC): non-dosimetry group
  • Small-Cell Lung Cancer (SCLC): non-dosimetry group All data presentations were to be presented primarily by the overall population but were also to be repeated split by tumor type where relevant. Some presentations were also to be repeated split by whether or not the patient was found to have tumors bearing GRPR expression according to cytology and/or histopathology findings.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Phase II Study of Preliminary Diagnostic Performance of [68Ga]-NeoBOMB1 in Adult Patients With Malignancies Known to Overexpress Gastrin Releasing Peptide Receptor (GRPR)
Actual Study Start Date : July 3, 2018
Actual Primary Completion Date : June 20, 2019
Actual Study Completion Date : July 5, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase II dosimetry group
All eligible participants were to receive recommended dose of [68Ga]-NeoBOMB1 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq. The maximum peptide mass administered was 50 microgram (µg)].
Drug: [68Ga]-NeoBOMB1
[68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors

Experimental: Phase II non-dosimetry group
All eligible participants were to receive recommended dose of [68Ga]-NeoBOMB1 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq. The maximum peptide mass administered was 50 microgram (µg)].
Drug: [68Ga]-NeoBOMB1
[68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors




Primary Outcome Measures :
  1. Number of lesions detected by [68Ga]-NeoBOMB1 [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the number of lesions identified by Positron Emission Tomography (PET) overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed.

  2. Number of Participants with Lesions detected by [68Ga]-NeoBOMB1 per Location [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the location of lesions identified by PET overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed.

  3. Non-Dosimetry Group: Standard Uptake Value (SUV) mean by timepoint and lesion location [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours) ]
    Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed.

  4. Non-Dosimetry Group: Standard Uptake Value (SUV) max by timepoint and lesion location [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.05 (only applicable for the Prostate Group), 1.50 and 2.50 hours) ]
    Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed.

  5. Dosimetry Group: Standard Uptake Value (SUV) mean by timepoint and lesion location [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) ]
    Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed.

  6. Dosimetry Group: Standard Uptake Value (SUV) max by timepoint and lesion location [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) ]
    Targeting properties of [68Ga]-NeoBOMB1 were to be evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET Imaging. The SUVmean and SUVmax (g/mL) of each lesion were to be calculated and reported by lesion location with summary statistics at all imaging time points. SUV was to be calculated overall and split by GRPR positive and negative patients, as well as by tumor type. Only descriptive analysis performed.

  7. Dosimetry Group: Evaluation of percentage of injected dose reaching the target (TACs) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 (0.15, 1.00, 2.00 and 4.00 hours) ]
    For patients included in the dosimetry group, the percentage of injected dose reaching source organs and tumor lesions was to be calculated using the acquired PET images at each time point. The resulting TACs were to be summarized descriptively.


Secondary Outcome Measures :
  1. Treatment Emergent Adverse Events profile [ Time Frame: From first dosing (single administration, Day 1) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. ]
    Treatment-emergent adverse events (TEAEs) were collected from first dosing (single administration, Day 1) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Grade 3/4/5 TEAEs, Serious Adverse Event TEAEs, Interruption of [68Ga]-NeoBOMB1 Due to Any TEAEs and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.

  2. Number of lesions detected by Conventional Imaging [ Time Frame: Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the number of lesions identified by Positron Emission Tomography (PET) overall and split by GRPR positive and negative patients, as well as by tumor type. The number of lesions identified by aforementioned PET imaging were to be compared with the number of lesions identified by the comparable conventional imaging. Only descriptive analysis performed.

  3. Number of Participants with Lesions detected by Conventional imaging per Location [ Time Frame: Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    The preliminary targeting properties of [68Ga]-NeoBOMB1 were to be assessed by summarizing the location of lesions identified by PET overall and split by GRPR positive and negative patients, as well as by tumor type. The location of lesions identified by aforementioned PET imaging were to be compared with the location of lesions identified by the comparable conventional imaging. Only descriptive analysis performed.

  4. Lesion-level analyses of diagnostics by [68Ga]-NeoBOMB1 compared with conventional imaging [ Time Frame: Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]

    At lesion level, overall, positive, and negative agreement of [68Ga]-NeoBOMB1 were to be calculated based on the aforementioned tabulations as follows:

    • Overall agreement = 100% x (Double positive + Double negative) / total number of lesions identified by either imaging proceduresg
    • Positive agreement = 100% x Double positive / (Double positive + Comparator single positive)
    • Negative agreement = 100% x Double negative / (Double negative + Comparator single negative).

  5. Patient-level analyses of diagnostics by [68Ga]-NeoBOMB1 compared with conventional imaging [ Time Frame: Conventional imaging collected within 3 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    At patient level, positive agreement was defined as the proportion of subjects with at least one lesion detected by conventional imaging in the specified location that also have at least one lesion detected by [68Ga]-NeoBOMB1. Overall agreement was defined as the proportion of subjects with at least one lesion detected in either imaging in the specified location that also have at least one lesion detected by [68Ga]-NeoBOMB1.

  6. Organ-level analyses of Diagnostics by [68Ga]-NeoBOMB1 compared to histological evidence [ Time Frame: Biopsy specimen collected within 6 months prior to study entry up to [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]

    The diagnostic performance of [68Ga]-NeoBOMB1 to GRPR overexpressing malignancies (lesions) was to be compared with cytology and/or histopathology findings from archival and/or recent biopsy specimens.

    Since the biopsy was performed on 1 lesion (collected either in primary or in metastatic tumors), a direct link may not be possible in case of multiple lesions per organ identified on [68Ga]-NeoBOMB1-PET. In this event, the determination of positive versus negative lesions on [68Ga]-NeoBOMB1-PET was done at organ level, i.e., if any lesion is positive in that organ, then the organ was to be considered positive. The sensitivity and specificity were to be calculated as follows: Sensitivity = 100% x True positive / (True positive + False negative); Specificity = 100% x True negative / (True negative + False positive).


  7. Dosimetry Group: absorbed dose in tumor [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    The absorbed dose in tumor and the effective radiation dose were to be summarized with descriptive statistics. Lesion number were assigned by dosimetry expert.

  8. Dosimetry Group: Effective whole-body dose [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    The absorbed dose in tumor and the effective radiation dose were to be summarized with descriptive statistics.

  9. Dosimetry Group: half-life of [68Ga]-NeoBOMB1 in blood (T^1/2) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  10. Dosimetry Group: Time of maximum observed drug concentration occurrence (Tmax) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  11. Dosimetry Group: Observed maximum plasma concentration (Cmax) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  12. Dosimetry Group: Area Under the plasma concentration-time Curve from the time 0 to the last observed quantifiable concentration (AUC(0-t)) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  13. Dosimetry Group: AUC(0-t) divided by the dose administered (AUC(0-t)/D) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  14. Dosimetry Group: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  15. Dosimetry Group: Total systemic clearance for intravenous administration (CL) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Venous whole blood samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters (Cmax, tmax, AUC(0-t), AUC(0-t)/D, t1/2, AUC(0-inf), CL) were to be listed and summarized using descriptive statistics.

  16. Dosimetry Group: Urinary excretion of [68Ga]-NeoBOMB1 (Vd) [ Time Frame: [68Ga]-NeoBOMB1 PET imaging acquired at Day 1 ]
    Urine samples were collected for activity-based pharmacokinetics characterization in the dosimetry group. PK parameters Vd was to be listed and summarized using descriptive statistics; as the total volume of excreted urine was not recorded, no percentage of urinary excretion could be calculated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be at least 18 years of age
  • Subjects must have signed and dated an informed consent prior to any study-specific procedures
  • Subjects with histologically-confirmed tumor for whom a recent biopsy (not older than 6-months old) has been performed.
  • Dosimetry group: luminal breast cancer, adenocarcinoma of the prostate
  • Non-dosimetry group: luminal breast cancer, adenocarcinoma of the prostate, small cell lung cancer, non-small cell lung cancer, colorectal carcinoma
  • At least one malignant lesion detected via functional or morphological imaging (PET combined to appropriate tracer according to tumor type, CT, MRI) within 3 months prior to [68Ga]-NeoBOMB1 administration
  • The Eastern Cooperative Oncology (ECOG) performance status 0-2.
  • Subjects must agree to use highly effective methods of contraception (female partners of male participants should use highly effective methods of contraception) during the trial.

Exclusion Criteria:

  • renal insufficiency or an eGFR <50 ml/min/1.73m2
  • hematological toxicity grade > 2 (Toxicity Grading Scale in vaccine clinical trials)
  • participation in any other investigational trial within 30 days of study entry
  • subjects with positive pregnancy test (urine dipstick), and/or currently breast-feeding
  • concurrent severe illness or clinically relevant trauma within 2 weeks before the administration of the investigational product that might preclude study completion or interfere with study results
  • concurrent bladder outflow obstruction or unmanageable urinary incontinence
  • known or expected hypersensitivity to [68Ga]-NeoBOMB1 or any excipient present in [68Ga]-NeoBOMB1
  • any condition that precludes raised arms position
  • prior administration of a radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide
  • history of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study

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): NCT03724253


Locations
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Austria
Medical University Innsbruck Department of Nuclear Medicine
Innsbruck, Austria
France
University of Grenoble - Hopital Michallon, Service de Medicine Nucleaire
La Tronche, France
University of Bordeaux, Unite TEP RECHERCHE - Hopital Xavier Arnozan
Pessac, France
Sponsors and Collaborators
Advanced Accelerator Applications
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Advanced Accelerator Applications
ClinicalTrials.gov Identifier: NCT03724253    
Other Study ID Numbers: A005D-E01-201
2017-003432-37 ( EudraCT Number )
CAAA503A12201 ( Other Identifier: Novartis )
First Posted: October 30, 2018    Key Record Dates
Last Update Posted: June 12, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Advanced Accelerator Applications:
[68Ga]-NeoBOMB1
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms