Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE October 21, 2018
First Posted Date  ICMJE October 30, 2018
Last Update Posted Date June 12, 2020
Actual Study Start Date  ICMJE July 3, 2018
Actual Primary Completion Date June 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 26, 2018)
  • distribution of tumor lesions identified by [68Ga]-NeoBOMB1 [ Time Frame: 6 weeks ]
    distribution of tumor lesions detected
  • percentage absorbed dose of [68Ga]-NeoBOMB1 [ Time Frame: 6 weeks ]
    percentage absorbed dose for overall and specific types of tumors
  • Tumor/background standardized uptake value (SUV) of [68Ga]-NeoBOMB1 [ Time Frame: 6 weeks ]
    ratio between tumor and background tumor uptake of [68]Ga-NeoBOMB1
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2020)
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2018)
  • Adverse events [ Time Frame: 6 weeks ]
    adverse events
  • decay corrected tissue time activity curves (TACs) [ Time Frame: 6 weeks ]
  • half-life of [68Ga]-NeoBOMB1 in blood [ Time Frame: 6 weeks ]
  • Non-decay-corrected TACs from [68Ga]-NeoBOMB1 PET/CT images in normal organs, tumor lesions [ Time Frame: 6 weeks ]
  • residence times in organs and tumor lesions [ Time Frame: 6 weeks ]
  • absorbed dose [ Time Frame: 6 weeks ]
  • whole body dose [ Time Frame: 6 weeks ]
  • SUV for each lesion [ Time Frame: 6 weeks ]
  • Urinary excretion of [68Ga]-NeoBOMB1 [ Time Frame: 6 weeks ]
  • distribution of tumors identified by [68Ga]-NeoBOMB1 compared to standard imaging modalities such as fludeoxyglucose Positron Emission Tomography [F18]FDG-PET [ Time Frame: 6 weeks ]
  • overall positive and negative agreement for [68Ga]-NeoBOMB1 PET compared to standard imaging on patient and tumor lesion level [ Time Frame: 6 weeks ]
  • compare positive and negative agreement for [68Ga]-NeoBOMB1 PET compared to cytology and/or histopathology from archival and/or recent biopsy specimens on patient and tumor lesion level [ Time Frame: 6 weeks ]
  • sensitivity of [68Ga]-NeoBOMB1 PET on a lesion by lesion basis compared to biopsy data [ Time Frame: 6 weeks ]
  • specificity of [68Ga]-NeoBOMB1 PET on a lesion by lesion basis compared to biopsy data [ Time Frame: 6 weeks ]
  • sensitivity of [68Ga]-NeoBOMB1 PET on a patient basis relative to histopathology/cytology data [ Time Frame: 6 weeks ]
  • specificity of [68Ga]-NeoBOMB1 PET on a patient basis relative to histopathology/cytology [ Time Frame: 6 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 26, 2018)
  • estimated absorbed [177Lu]-NeoBOMB1 dose extrapolated from [68Ga]-dosimetric data [ Time Frame: 6 weeks ]
  • define limiting organ for radionuclide therapy [ Time Frame: 6 weeks ]
 
Descriptive Information
Brief Title  ICMJE [68Ga]-NeoBOMB1 Imaging in Patients With Malignancies Known to Overexpress Gastrin Releasing Peptide Receptor (GRPR)
Official Title  ICMJE Phase II Study of Preliminary Diagnostic Performance of [68Ga]-NeoBOMB1 in Adult Patients With Malignancies Known to Overexpress Gastrin Releasing Peptide Receptor (GRPR)
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).
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Breast Cancer
  • Prostate Cancer
  • Colorectal Cancer
  • Non Small Cell Lung Cancer
  • Small Cell Lung Cancer
Intervention  ICMJE Drug: [68Ga]-NeoBOMB1
[68Ga]-radiolabeled bombesin peptide targeting Gastrin Releasing Peptide Receptors
Study Arms  ICMJE
  • 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)].
    Intervention: Drug: [68Ga]-NeoBOMB1
  • 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)].
    Intervention: Drug: [68Ga]-NeoBOMB1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 22, 2019)
19
Original Estimated Enrollment  ICMJE
 (submitted: October 26, 2018)
50
Actual Study Completion Date  ICMJE July 5, 2019
Actual Primary Completion Date June 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03724253
Other Study ID Numbers  ICMJE A005D-E01-201
2017-003432-37 ( EudraCT Number )
CAAA503A12201 ( Other Identifier: Novartis )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Responsible Party Advanced Accelerator Applications
Study Sponsor  ICMJE Advanced Accelerator Applications
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Advanced Accelerator Applications
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP