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Trial registered on ANZCTR


Registration number
ACTRN12621000301864
Ethics application status
Approved
Date submitted
20/01/2021
Date registered
18/03/2021
Date last updated
21/04/2023
Date data sharing statement initially provided
18/03/2021
Date results information initially provided
31/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2 Study to Evaluate the Dosing and Timing of VGT-309, a Tumor-Targeted Fluorescent Imaging Agent for the Identification of Lung Cancer
Scientific title
A Phase 2, Open-label Study to Evaluate the Safety, Efficacy, Dosing, and Timing of VGT-309, a Tumor-Targeted, Activatable Fluorescent Imaging Agent for the Intraoperative Identification of Lung Cancer
Secondary ID [1] 303125 0
Protocol VGT-309-2-2021AUS
Universal Trial Number (UTN)
Trial acronym
Linked study record
This is a follow-on study to record ACTRN12620000948998

Health condition
Health condition(s) or problem(s) studied:
Lung Cancer 320229 0
Condition category
Condition code
Cancer 318165 318165 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 24 men or women who are scheduled to undergo surgical resection or excisional biopsy of a lung nodule that is suspicious for, or proven to be, lung cancer was enrolled in this study in 4 dose cohorts.

Subjects were sequentially assigned into one of four cohorts as detailed below. Within each of Cohorts 1 to 3, subjects were dosed either 12 to 36 hours or 2 to 6 hours before surgery depending on their admission to the hospital. The split into each of the dosing time windows was not be equal but best efforts will be made to ensure that a minimum of two subjects at each dose level are assigned to a dosing window. In Cohort 4, approximately 6 subjects were given the dose of VGT-309 and dose timing identified as the optimal dose that is safe and gives the best visualisation of the tumor.
VGT-309 was administered as a single intravenous infusion over 15 to 20 minutes. Doses of VGT-309 were administered in hospital under medical supervision.The doses for this study were:
Cohort 1: 0.05 mg/kg given either 12-36 hours pre-op or 2-6 hours pre-op
Cohort 2: 0.16 mg/kg given either 12-36 hours pre-op or 2-6 hours pre-op
Cohort 3: 0.32 mg/kg given either 12-36 hours pre-op or 2-6 hours pre-op
Cohort 4: Optimal dose defined in Cohort 1 as a safe dose that produces the best visualisation of the tumor.
The recruitment for cohort 1-4 was completed in May2022.

Additional 20 men or women who are scheduled to undergo surgical resection or excisional biopsy of a lung nodule that is suspicious for, or proven to be, lung cancer will now be enrolled in this study in the cohort 5 and 6 for extension phase 2 study. Recruitment for cohort 5 and 6 is scheduled to commence Apr2023.
In Cohort 5 to 6 , approximately 20 subjects will be given the dose of VGT-309 and dose timing identified as the optimal dose that is safe and gives the best visualisation of the tumor.

The doses for this study are
Cohort 5: 0.5 mg/kg given either 12-36 hours pre-op or 2-6 hours pre-op
Cohort 6: 0.64 mg/kg given either 12-36 hours pre-op or 2-6 hours pre-op
Intervention code [1] 319424 0
Treatment: Other
Intervention code [2] 319769 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326151 0
Number of times the surgeon is able to visualize the tumour when using near-infrared fluorescence imaging with VGT-309
Timepoint [1] 326151 0
At the time of surgery
Primary outcome [2] 326152 0
To evaluate the safety of VGT-309 through the assessment of: treatment-emergent adverse events assessed through regular solicitation of subjects and review of physical examination data, vital sign data including blood pressure measured using a digital blood pressure monitor, heart rate measured as beats per minute, temperature and respiratory rate measured as breaths per minute, ECG data and clinical laboratory assessments of blood and urine: hematology (standard panel), coagulation (INR only), chemistry (standard panel including LFTs and amylase)
Timepoint [2] 326152 0
Treatment-emergent adverse events will be collected from the time of dosing on Day 1 through the Day 28 to Day 35 final safety follow-up visit
Physical examinations will be conducted at screening, on Day 1, Day 4, and Day 28-35
Clinical laboratory assessments of blood and urine will be collected at screening, on screening, on Day 1, Day 4, and Day 28-35
ECGs will be collected at screening, on Day 1, Day 4, and Day 28-35.
Vital signs will be collected at screening, on Day 1, at time of surgery on Day 1 or Day 2, Day 4, and Day 28-35.
Primary outcome [3] 326591 0
To determine the quality or intensity of the fluorescence of the visualised tumours when using near-infrared fluorescence imaging with VGT-309
Timepoint [3] 326591 0
At the time of surgery
Secondary outcome [1] 390257 0
Comparison of tumor-to-background ratio (TBR) in ex vivo surgical specimen(s) from subjects receiving 2 additional VGT-309 doses
Timepoint [1] 390257 0
At time of surgery
Secondary outcome [2] 390258 0
Proportion of subjects requiring VGT-309 and NIR imaging to detect a primary lung lesion that could not be detected after 5 minutes with standard surgical techniques
Timepoint [2] 390258 0
At time of surgery
Secondary outcome [3] 390259 0
Comparison of the estimated depth from the surface of the lung of CT- visible lesions to those detectable from the surface of the lung during use of VGT-309 NIR fluorescent imaging
Timepoint [3] 390259 0
At time of surgery
Secondary outcome [4] 390260 0
Comparison of the rate of positive tumor surgical margins detected by VGT-309 NIR fluorescence imaging to the rate by standard frozen section analysis
Timepoint [4] 390260 0
At the time of surgery
Secondary outcome [5] 390261 0
Comparison of the rate of positive tumor margins detected by VGT-309 NIR fluorescence imaging to the rate by standard formalin-fixed paraffin-embedded (FFPE) sampling
Timepoint [5] 390261 0
Within 24 hours post surgery
Secondary outcome [6] 421121 0
To investigate the influence, if any, of the higher doses, at peak serum concentration on the timing and morphology of the electrocardiogram.
Timepoint [6] 421121 0
Four blood samples to be taken immediately prior to dosing with VGT-309,
within 10 minutes of completion of dosing, 30 minutes after completion of
dosing and, when possible, within 60 minutes prior to the start of surgery.
(Refer to Schedule of Assessments for details)

Eligibility
Key inclusion criteria
1. Be willing and able to sign the informed consent and comply with study procedures
2. Be at least 18 years of age
3. Be scheduled to undergo planned standard of care surgical resection for a lung nodule or mass, whether or not it is biopsy-proven
4. Have an ECOG score of 0-1
5. Have an acceptable hematologic and coagulation status and kidney and liver functions at study entry
6. Be male or female and meet the following conditions:
a. Female participants must be of non-childbearing potential, or,
b. If of childbearing potential be non-pregnant or lactating and agree to use highly effective contraception from screening through Day 30.
c. Male participants, if not surgically sterilized, and if engaging in sexual intercourse with a female partner of childbearing potential, must be willing to use highly effective contraception from screening through 90 days post-dose and agree not to donate semen during this waiting period.
d. Highly effective contraception involves the use of a condom for the male, plus one of the following for the female:
- Oral, injectable, implantable, intravaginal, or transdermal hormonal contraceptives, or
- Intrauterine device or intrauterine hormone-releasing system
NOTE: Participants who abstain from heterosexual intercourse as their usual and preferred lifestyle, will not be required to use contraception as described above. They are required to maintain abstinence from screening through Day 30.
7. Are judged to be an acceptable surgical risk by the operating surgeon and the anesthesiologist/anesthetist.
8. Have not participated in a clinical trial within the last 30 days.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have a history of myocardial infarction, cerebrovascular accident, uncontrolled congestive heart failure, significant liver disease, or unstable angina within 6 months prior to enrollment.
2. Have any other condition that causes the Investigator to deem them unfit for lung resection.
3. Are receiving a Class IA (i.e. quinidine, procainamide) or Class III (i.e. dofetilide, amiodarone, sotalol) antiarrhythmic agents
4. Have congenital long QT syndrome or QTcF > 450 ms (males) or >470 ms (females) by history or at Screening ECG.
5. Have a history or evidence of interstitial pneumonitis or pulmonary fibrosis
6. A known allergy or reaction to ICG or other radiographic contrast agents
7. Any other co-morbidity or habit that the Investigator believes will interfere with their ability to comply with and complete the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Open label ascending dose study.
When subjects are deemed eligible for study entry, they were assigned to one of 4 cohorts.
Cohort 1, 2, 3 had 6 subjects assigned to each cohort and 1 of 2 dosing time windows. Cohort 4 had approximately 6 subjects given the dose and dose timing identified as optimal. Cohort 1-4 completed in May2022.

Cohort 5 and 6 will have 10 subjects assigned to each dose and recruitment is scheduled to begin in Apr2023.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This is an early development study and therefore no formal sample size calculations were involved in the sample size determination.

Statistical analyses for both safety and efficacy will be primarily descriptive.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/05/2021
Actual
11/05/2021
Date of last participant enrolment
Anticipated
12/09/2023
Actual
Date of last data collection
Anticipated
16/10/2023
Actual
Sample size
Target
44
Accrual to date
27
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18379 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 18380 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [3] 24591 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment postcode(s) [1] 40186 0
3052 - Parkville
Recruitment postcode(s) [2] 32459 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 307534 0
Commercial sector/Industry
Name [1] 307534 0
Vergent Bioscience Australia, Pty Ltd
Country [1] 307534 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Vergent Bioscience Australia, Pty Ltd
Address
c/o Case Governance Pty Ltd
Level 13
41 Exhibition Street
Melbourne, VIC, 3000
Country
Australia
Secondary sponsor category [1] 308212 0
None
Name [1] 308212 0
Address [1] 308212 0
Country [1] 308212 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307600 0
St Vincent's Hospital Melbourne Human Research Ethics Committee
Ethics committee address [1] 307600 0
Research Governance Unit
Level 5, Building E (Aikenhead Building)
27 Victoria Parade
Fitzroy VIC 3065
Ethics committee country [1] 307600 0
Australia
Date submitted for ethics approval [1] 307600 0
01/03/2021
Approval date [1] 307600 0
27/04/2021
Ethics approval number [1] 307600 0

Summary
Brief summary
This study is to look at the efficacy and safety of VGT-309, a tumour targeted imaging agent, when used intra-operatively in subjects with scheduled surgical resection or biopsy of suspicious or proven lung cancer

Who is it for?
You may be eligible for this study if you are an adult man or woman at least 18 years of age and you are scheduled to undergo surgical resection or excisional biopsy (per standard of care) of a lung nodule that is suspicious for, or proven to be, lung cancer.

Study details
If you meet the entry criteria you will be assigned to one of two dosing cohorts and will receive a single dose of VGT-309 which will be given to you as in intravenous infusion over a period of 15 to 20 minutes either 12-36 hours before your surgery or 2-6 hours before your surgery. Total participation will last about 35 days (not including the 28 day screening period) and during this time for safety you will have blood and urine samples drawn, your vital signs will be checked, you will have physical examinations and ECGs will be conducted.

It is hoped this research will enable doctors in the future to use VGT-309 as an intraoperative fluorescent imaging agent to identify lung cancer compared to surrounding normal tissue
Trial website
https://www.vergentbio.com/
Trial related presentations / publications
Public notes
not available yet

Contacts
Principal investigator
Name 53430 0
A/Prof Gavin Wright
Address 53430 0
Director of Surgical Oncology
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy, Victoria 3065
Country 53430 0
Australia
Phone 53430 0
+61 3 9419 2477
Fax 53430 0
Email 53430 0
gavin.wright@svha.org.au
Contact person for public queries
Name 53431 0
A/Prof Gavin Wright
Address 53431 0
Director of Surgical Oncology
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy, Victoria 3065
Country 53431 0
Australia
Phone 53431 0
+61 3 9419 2477
Fax 53431 0
Email 53431 0
gavin.wright@svha.org.au
Contact person for scientific queries
Name 53432 0
A/Prof Gavin Wright
Address 53432 0
Director of Surgical Oncology
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy, Victoria 3065
Country 53432 0
Australia
Phone 53432 0
+61 3 9419 2477
Fax 53432 0
Email 53432 0
gavin.wright@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Information is not yet available


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo VGT-309 was shown to be well-tolerated with few si... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AICathepsin detection to identify malignant cells during robotic pulmonary resection2023https://doi.org/10.21037/tlcr-23-370
Dimensions AIFluorescent Probes for Imaging in Humans: Where Are We Now?2023https://doi.org/10.1021/acsnano.3c03564
N.B. These documents automatically identified may not have been verified by the study sponsor.