COVID-19 studies are our top priority.

For new and updated trial submissions, we are processing trials as quickly as possible and appreciate your patience. We recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621000301864p
Ethics application status
Submitted, not yet approved
Date submitted
20/01/2021
Date registered
18/03/2021
Date last updated
18/03/2021
Date data sharing statement initially provided
18/03/2021
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 will be enrolled in this study in 4 dose cohorts.

Subjects will be sequentially assigned into one of four cohorts as detailed below. Within each of Cohorts 1 to 3, subjects will be 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 will 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 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.

VGT-309 will be administered as a single intravenous infusion over 15 to 20 minutes. Doses of VGT-309 will be administered in hospital under medical supervision.

The doses for this study are
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
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
Specificity of VGT-309 for the tumour compared to the surrounding tissue as measured by a comparison of tumour-to-background ratio in ex vivo surgical specimen(s) taken from subjects receiving three different doses of VGT-309.
The analysis is done on the complete excised surgical specimen where fluorescence under NIR light will be measured using a Stryker SPY-PHI handheld NIR imaging system or equivalent. The same analysis will then take place using Formalin fixed tissue sections stained with hematoxylin and eosin (H&E) which will be used to diagnosis identify the malignant cells under white light. . The tumour-to-background ratio will be calculated by dividing the fluorescence intensity of tumour by the fluorescence intensity of surrounding normal tissue.
Timepoint [1] 390257 0
At time of surgery
Secondary outcome [2] 390258 0
To assess the ability of fluorescence imaging with VGT-309 under NIR to help the surgeon identify the primary tumour and any other areas of fluorescence, such as in lymph nodes, more rapidly to allow for the surgery to be completed more expeditiously while also optimizing the complete resection of tumour at the initial operation. This will be through a comparison of the proportion of subjects requiring VG-309 and near-infrared 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
To assess the strength of the fluorescence image by measuring how deep the overlying normal tissue can be before the fluorescence signal is no longer observed. A comparison will be made 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 near-infrared fluorescent imaging.
Timepoint [3] 390259 0
At time of surgery
Secondary outcome [4] 390260 0
The goal for curative cancer surgery is to completely remove all traces of the tumor. At the time of surgery the pathologist regularly takes small sections at the edge of the surgical resection to flash freeze them and then look under the microscope for any sign that the tumor extends to the edge of the surgical margin. If the pathologist finds tumor, the surgeon extends the surgical margin until it is determined that no more tumor is seen or the limits of surgical resection are reached. If any tumor is not removed at the initial surgery if is known that the survival of the patient is negatively impacted. In this study the pathologist will do standard of care surgical margin examination using flash frozen tissue stained with H&E and report back to the surgeon. The rate of positive margins predicted by NIR fluorescent imaging of the excised surgical specimen in the operating room will be compared to positive surgical margins predicted by frozen section analysis.
Timepoint [4] 390260 0
At the time of surgery
Secondary outcome [5] 390261 0
To assess the rate efficiency of finding positive surgical margins using standard of care and VGT-309. The standard of care is to assess the tumour margins in formalin fixed tissue slides stained with H&E. After the analysis of the tissue is made using standard H&E, the pathologist will observe the fluorescence pattern, to allow a comparison to be made of the rate of positive tumour margins detected by VGT-309 near-infrared fluorescence imaging compared to standard formalin-fixed paraffin-embedded sampling.
Timepoint [5] 390261 0
Within 24 hours post surgery

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
Gender
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 will be assigned to one of 2 cohorts. Cohort 1 will have 3 sub-groups defined by ascending dose. Within each subgroup, subjects will be assigned to 1 of 2 dosing times (12 to 36 hours pre-op or 2-6 hours pre-op). Cohort 2 subjects will be given the dose and dose timing identified as optimal.
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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
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 postcode(s) [1] 32459 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 307534 0
Commercial sector/Industry
Name [1] 307534 0
Vergent Bioscience Australia, Pty Ltd
Address [1] 307534 0
c/o Case Governance Pty Ltd
Level 13
41 Exhibition Street
Melbourne, VIC, 3000
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
Submitted, not yet 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
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
Trial related presentations / publications
Public notes

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
What supporting documents are/will be available?
No other documents available
Summary results
No Results