Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000787482
Ethics application status
Approved
Date submitted
14/06/2016
Date registered
16/06/2016
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Date results provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and tolerability of MIL-38/ Gallium67 (MILGa) in patients with advanced prostate, bladder and pancreatic cancer.
Scientific title
MILGa-01: A first in human study to evaluate the safety and tolerability of monoclonal antibody conjugate MILGa (MIL-38/Gallium67) in patients with advanced prostate, bladder and pancreatic cancer.
Secondary ID [1] 289437 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MILGa-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 299127 0
Pancreatic cancer 299128 0
Bladder cancer 299129 0
Condition category
Condition code
Cancer 299147 299147 0 0
Bladder
Cancer 299148 299148 0 0
Prostate
Cancer 299149 299149 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational product “MILGa” is a chimeric MIL-38 monoclonal antibody targeting GPC-1, which has been chemically conjugated with the chelating agent DOTA and labeled with the radioisotope Gallium 67 (67Ga). MILGa is being developed for imaging metastases in prostate, pancreatic and bladder cancer patients. A total volume of 3-8ml (1mg of antibody at an activity of 250mBq) will be infused via slow IV push. The use of the chimeric MIL-38 monoclonal antibody conjugated to DOTA and labelled with 67Ga is safe and clinically useful for the detection of advanced prostate, bladder and pancreatic tumours. The addition of unlabelled chMIL-38-DOTA will aim to minimise binding of chMIL-38-DOTA-67Ga to non-tumour sites. The initial cohort of 3 patients will receive a 250 MBq imaging dose of chMIL-38-DOTA-67Ga.
Cohort 1 (Patients 1, 2 and 3)
*Patient 1: inpatient treatment with continuous monitoring for 48 to 72 h
*Patient 2: Four weeks after patient 1, inpatient treatment with continuous monitoring for 24 to 48 h
*Patient 3: Four weeks after patient 2, inpatient treatment with continuous monitoring for 24 to 48 h

Cohort 2 (Patients 4, 5 and 6)
Patients in this cohort will be infused with 3.5 mg of unlabelled chMIL-38-DOTA one hour prior to receiving 1 mg chMIL-38-DOTA labelled with 250 MBq 67Ga. Each patient in this cohort will be dosed 2 weeks apart and images using planar whole body scans and SPECT/CT.

Cohort 3 (Patients 7, 8 and 9)
Patients in this cohort will be infused with an incrementally higher dose within the range of 3.5 mg and 24 mg of unlabelled chMIL-38-DOTA one hour prior to receiving 1 mg chMIL-38-DOTA labelled with 250 MBq 67Ga. Each patient in this cohort will be dosed 2 weeks apart and images using planar whole body scans and SPECT/CT.

Cohort 4 (Patients 10, 11 and 12)
Patients in this cohort will be infused with an incrementally higher dose within the range of 3.5 mg and 24 mg of unlabelled chMIL-38-DOTA one hour prior to receiving 1 mg chMIL-38-DOTA labelled with 250 MBq 67Ga. Each patient in this cohort will be dosed 2 weeks apart and images using planar whole body scans and SPECT/CT.

At end of each cohort: Safety assessment by DSMC and preliminary assessment of chMIL-38-DOTA-67Ga scan utility will be determined. Furthermore, the effect of the dose of un-labelled chMIL-38-DOTA used per cohort on tumour targeting will be reviewed at the end of each cohort to determine the unlabelled antibody dose for the subsequent cohort.

Targeting of MILGa to patient’s metastases will be assessed by planar gamma imaging and SPECT/CT and compared to known metastases identified by standard of care imaging. Standard of care scans will be taken on the day of screening (visit 1) up to 14 days prior to MILGa infusion.
Planar whole body and SPECT/CT imaging studies are planned as follows:
*Transmission whole body scan with Cobalt-57 phantom prior to infusion with patient and without patient
*Planar whole body imaging and, if required, SPECT/CT at T 30mins post infusion
*Planar whole body imaging and, if required, SPECT/CT at T6h post infusion
*Planar whole body imaging and SPECT/CT at T24h
*Planar whole body imaging and, if required, SPECT/CT at T48h
*Planar whole body imaging and, if required, SPECT/CT at T72h (Day 3)
*Planar whole body imaging and SPECT/CT at T144h (Day6)
*Planar whole body imaging at 2 weeks post infusion (if required)
Any potential metastatic lesion identified on MILGa scanning but not visible on routine scans may be followed by standard radiology and, if possible, be biopsied later.
Scan parameters:
*Whole Body scan step-and-shoot, tri window of 300keV, 184keV and 93 with a window of +/- of 13%, 10%, 10%; Medium Energy Collimators; 180 second per step/bed-length. Whole body acquisition at 6hours, 24hours, 48hours, 72hours with the potential for further scans if required.
*SPECT/CT: tri window of 300keV, 184keV and 93 with a window of +/- of 13%, 10%, 10% and a scatter correction window of 75 with a +/- window of 7%; Medium Energy Collimators; Step and Shoot 60/frames (or 6 degree intervals); 30second acquisition per step; Matrix 512x512; Attenuation Correction CT only; at 24hours and possibly 48hours.
*Transmission whole body scans with Cobalt-57 phantom prior to patient infusion. One scan will be conducted with the patient, followed by a second scan without the patient. Each scan is approximately 25 minutes. The transmission whole body scan will be carried out for attenuation correction for isodosing of tissue. A nuclear medicine physicist will measure this.
Intervention code [1] 295047 0
Early detection / Screening
Comparator / control treatment
No control group however standard of care scans and baseline scans will be taken for each patient prior to MILGa infusion. MILGa scans for each tumour type will be compared with a standard of care imaging scan which includes a technetium bone scan for prostate cancer and CT scan of chest, abdomen and pelvis for prostate, pancreas and urothelial cancers. this will be carried out up to 14 days prior to MILGa infusion. Additionally, before MILGa infusion a study radiologist will identify the metastatic lesions radiologically using standard of care scans (CT and bone scan) Whole body SPECT/CT scans will be taken post drug infusion at T30 minutes, T6 hours, T24 hours, T48 hours and T72 hours. Blood will also be collected for haematology and biochemistry analysis as well as tumour markers (CA-19.9/ CEA/ PSA).
Control group
Active

Outcomes
Primary outcome [1] 298627 0
To determine the safety/tolerability of MILGa during infusion and post infusion. Safety and tolerability will be assessed by the following parameters: vital signs, 12-lead ECGs and blood draws, biomarker blood draws, urinalysis, haematology and biochemistry blood analysis and physical examination. Additional time points for safety tests such as vital signs, physical exams and laboratory safety tests may be added during the course of the study based on newly available data to ensure appropriate safety monitoring. Prior to dose administration for all patients, higher dependency unit bed in ICU/CCU will be arranged for patient monitoring. Dose administration will be performed in an advanced life support equipped area with dedicated medical staff at hand. The first patient will be monitored as an inpatient for the first 48 h. Assuming a good safety profile for Patient 1, Patients 2-12 will be monitored as an inpatient for the first 24 h post infusion. All patients will be closely monitored post infusion to identify and manage immediate hypersensitivity organ reactions.
Timepoint [1] 298627 0
Post MILGa drug infusion at T30minutes, T6 hours, T24 hours, T48 hours, T72 hours, T144hours, T2 weeks, T3 weeks and T4 weeks.
Secondary outcome [1] 324801 0
To qualitatively evaluate the utility of chMIL-38-DOTA-67Ga as a diagnostic tool in prostate, bladder and pancreatic tumours.
This outcome will be assessed using standard blood test measurement, tumour biomarker levels and imaging tools (SPECT/CT and planar whole body imaging).
Timepoint [1] 324801 0
Post MILGa drug infusion at T30minutes, T6 hours, T24 hours, T48 hours, T72 hours, T144hours, T2 weeks, T3 weeks and T4 weeks.
Secondary outcome [2] 324802 0
To evaluate bio distribution and establish pharmacokinetics of chMIL-38-DOTA.
The outcome will be assessed using a serum-based PK assay and will be measured using absorbance units (AU).

Timepoint [2] 324802 0
Post MILGa drug infusion at T30minutes, T6 hours, T24 hours, T48 hours, T72 hours, T144hours, T2 weeks, T3 weeks and T4 weeks.
Secondary outcome [3] 331039 0
To establish the optimal dose of chMIL-38-DOTA.
This outcome will be assessed using dosimetry analysis and PK assessment using a serum based assay analysis.
Timepoint [3] 331039 0
Post MILGa drug infusion at T30minutes, T6 hours, T24 hours, T48 hours, T72 hours, T144hours, T2 weeks, T3 weeks and T4 weeks.

Eligibility
Key inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
*Written informed consent provided.
*18 years old or older.
*Histologically or cytologically confirmed diagnosis of
a. Prostate cancer
b.Urothelial cancer (bladder, ureter, urethra, renal pelvis)
c.Pancreatic cancer
*Metastatic disease as assessed by CT, bone, or MRI within 14 days of MILGa scan.
a. At least two metastases and up to 15 metastases
b.Stable or slowly progressing disease as determined by the Investigator
c.For prostate cancer the minimal standard scans is CT Chest/Abdomen/Pelvis (CAP) and whole body bone scan.
d.For urothelial and pancreas cancer the minimal standard scans is CT CAP.
* No change of anti-cancer therapy within 4 weeks of study entry and none planned for at least 2 weeks after study entry.
*Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale. Subjects with performance status of 2 may be enrolled in at the discretion of the Investigator.
*Male subjects must agree to use contraception methods. This criterion must be followed from the time of the dose of study medication until 4 weeks after.
*A female subject is eligible to participate if she is of:
a.Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and oestradiol < 40 pg/mL (<140 pmol/L) is confirmatory].
b.Child-bearing potential and agrees to use contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until four weeks after the last dose of study medication.
*Adequate organ system function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Patients with extensive bone marrow involvement as defined by abnormal haematological values or prostate cancer patients with “super scan” on standard imaging (nuclear bone scan)
2. Change in anti-cancer therapy planned for 4 weeks before or two weeks after MILGa scan.
3. Currently receiving cytotoxic chemotherapy that is expected to cause grade 3 neutropenia or grade 3 thrombocytopenia.
4. Patients with rapidly progressing metastatic disease as determined by the Principal Investigator
5. Any major surgery, radiotherapy or immunotherapy in the four weeks preceding MILGa dosing
6. Concurrent condition precluding the patient from following study protocol.
7. QTc interval of greater than 450 msec
8. Unwillingness or inability to follow study procedures.
9. Known immediate or delayed hypersensitivity reactions to study drug.

Study design
Purpose of the study
Diagnosis
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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The number of participant (n=12) was determined based on previous first-in-human Phase 1 immunotherapeutic imaging trials. The primary focus of this study will be on determining the safety and tolerability of MILGa in patients with advanced cancer. Most analyses will be descriptive or exploratory.
All available data including adverse events, changes in laboratory values and other safety and efficacy parameters will be evaluated for each tumour stream.
With respect to secondary objectives of evaluating the utility of MILGa as a diagnostic tool, we have allocated four patients per tumour stream estimating between two and fifteen lesions per patient with the hypothesis that the MILGa Ga67 scan will have a sensitivity/specificity of greater than 80% in identifying metastatic disease when compared to standard of care imaging.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
18/08/2016
Date of last participant enrolment
Anticipated
28/04/2018
Actual
28/04/2018
Date of last data collection
Anticipated
26/05/2018
Actual
26/05/2018
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5977 0
Macquarie University Hospital - Macquarie Park
Recruitment postcode(s) [1] 13399 0
2113 - Macquarie Park

Funding & Sponsors
Funding source category [1] 293812 0
Commercial sector/Industry
Name [1] 293812 0
Minomic International
Country [1] 293812 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Minomic International
Address
Ground Floor, Suite 2, 75 Talavera Road, Macquarie Park, NSW 2113
Country
Australia
Secondary sponsor category [1] 292642 0
None
Name [1] 292642 0
Address [1] 292642 0
Country [1] 292642 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295244 0
Macquarie University HREC Medical Sciences
Ethics committee address [1] 295244 0
Ethics committee country [1] 295244 0
Australia
Date submitted for ethics approval [1] 295244 0
07/03/2016
Approval date [1] 295244 0
28/06/2016
Ethics approval number [1] 295244 0
5201600149

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66674 0
Prof Howard Gurney
Address 66674 0
Suite 304, Level 3 2 Technology Place , Macquarie University, NSW, 2109
Country 66674 0
Australia
Phone 66674 0
+61 2 8850 8100
Fax 66674 0
Email 66674 0
[email protected]
Contact person for public queries
Name 66675 0
Brad Walsh
Address 66675 0
Minomic International
Suite 2, Ground Floor, 75 Talavera Road, Macquarie Park, NSW 2113
Country 66675 0
Australia
Phone 66675 0
+61 2 9850 4001
Fax 66675 0
Email 66675 0
[email protected]
Contact person for scientific queries
Name 66676 0
Douglas Campbell
Address 66676 0
Minomic International
Suite 2, Ground Floor, 75 Talavera Road, Macquarie Park, NSW 2113
Country 66676 0
Australia
Phone 66676 0
+61 2 9850 4002
Fax 66676 0
Email 66676 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Commercial in confidence


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRetroSPECT: Gallium-67 as a long-lived imaging agent for theranostics.2021https://dx.doi.org/10.22038/AOJNMB.2020.51714
EmbaseSafety and tolerability of miltuximab-a first in human study in patients with advanced solid cancers.2021https://dx.doi.org/10.22038/AOJNMB.2021.55600.1386
N.B. These documents automatically identified may not have been verified by the study sponsor.