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Trial registered on ANZCTR


Registration number
ACTRN12612000802808
Ethics application status
Approved
Date submitted
19/07/2012
Date registered
31/07/2012
Date last updated
5/02/2019
Date data sharing statement initially provided
5/02/2019
Date results information initially provided
5/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I Safety and Biodistribution Study of 124I-PEG-AVP0458 Diabody in Patients with TAG-72 Positive Ovarian and Prostate Cancer
Scientific title
Phase I Safety and Biodistribution Study of 124I-PEG-AVP0458 Diabody in Patients with TAG-72 Positive Ovarian and Prostate Cancer
Secondary ID [1] 280868 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian cancer 286938 0
Prostate cancer 286939 0
Condition category
Condition code
Cancer 287272 287272 0 0
Ovarian and primary peritoneal
Cancer 287273 287273 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I, open-label study of the safety and biodistribution of two escalating doses of PEG-AVP0458, labelled with 3-5 mCi of 124I for PET imaging.
This is the first study of PEG-AVP0458 in humans. The ultimate purpose of this research is to find better ways to detect and treat prostate and ovarian cancers. The product under investigation, PEG-AVP0458, has been designed to attach to a specific protein called TAG-72, which is found on the surface of some types of cancer cells however it is not a treatment for cancer. The aims of this study are to determine the safety of PEG-AVP0458 at the doses studied, and to demonstrate that PEG-AVP0458 can attach to the TAG-72 protein on prostate and ovarian cancer cells in humans. PEG-AVP0458 will be combined with a low dose radioactive iodine particle by a process called radiolabelling, and injected. The radiolabel acts as a tracer, which means that it can be detected in tissue by a special scanning system called a PET scan.
124I-PEG-AVP0458 is to be administered to patients by slow intravenous infusion over an hour, with safety monitoring during and for 4 hours post infusion. PET imaging will be performed post infusion of 124I-PEG-AVP0458 on Day 0, and on a further 4 occasions over a one week period.
The first three patients entered into this study will receive 1 mg/m2 of PEG-AVP0458 (the first dose level). If no patients entered in the 1st dose group experience a dose-limiting toxicity (DLT) then the next dose group may commence 30 days after the last patient on the previous dose group has received the 124I-PEG-AVP0458 infusion. If any one patient experiences a DLT, then 3 additional patients will be entered in the 1 mg/m2 dose group.
After completion of accrual into the first cohort (1 mg/m2 dose), a Trial Management Committee will review the safety data from these participants before a decision is made to escalate the dose to 10 mg/m2.
The second dose group of three patients will receive 10 mg/m2 (second dose level), and the amount of 124I radioactivity is kept constant at 3-5 mCi. If any one patient experiences a DLT, then 3 additional patients will be entered in the 10 mg/m2 dose group.
The last dose group of three patients will receive either 1 mg/m2 or 10 mg/m2. The dose will be determined by the Trial Management Committee following an interim analysis of safety data and the quality of imaging results obtained in the dose-escalation part of the study.
Intervention code [1] 285301 0
Treatment: Other
Intervention code [2] 285333 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287553 0
The primary objective of this clinical study is to evaluate the safety of a single dose of 124I-PEG-AVP0458 in patients with prostate and ovarian cancer.
Safety of 124I-PEG-AVP0458 will be determined by the ongoing monitoring of the incidence and intensity of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE), with special emphasis on DLT events and infusional toxicities. A copy of CTCAE v4.0 may be downloaded from the Cancer Therapy Evaluation Program home page.
A DLT is defined as any of the following events occurring within 30 days of study drug administration:
-Any Grade 2 or greater allergic reaction.
-Any Grade 3 toxicity. Exceptions are: fever; asymptomatic hyperglycemia; hypophosphatemia; nausea, vomiting, or diarrhoea despite the use of optimal supportive medical therapy; leukopenia or thrombocytopenia that revert to baseline within three weeks of occurrence; lymphopenia without other dose-limiting events (eg opportunistic infection).
-Any Grade 4 toxicity.
To be dose-limiting, a toxicity must be possibly, probably, or definitely related to the administration of 124I-PEG-AVP0458.
Safety monitoring includes vital signs (blood pressure, pulse, respiration, temperature), physical examination, 12 lead ECG, and blood tests.
There are no anticipated severe adverse events associated with the administration of the investigational product, which will be given as a one dose infusion.
Timepoint [1] 287553 0
Until 28 days following the end of treatment exposure
Secondary outcome [1] 298374 0
There are three secondary objectives for this study. The first is to evaluate biodistribution, including tumour targeting, of 124I-PEG-AVP0458 in patients with prostate and ovarian cancer.
Timepoint [1] 298374 0
To evaluate biodistribution, PET/CT whole body imaging will be performed at the following 5 time-points upon administration of 124I-PEG-AVP0458: Day 0 (approximately 1 hour after infusion), day 1, day 2 or 3, day 4 or 5, and day 6 or 7.
Secondary outcome [2] 298473 0
Pharmacokinetics will also be evaluated in this study, measuring both administered radioactivity and the PEG-AVP0458 protein.
Timepoint [2] 298473 0
To evaluate the way the drug is moved around the body, blood samples will be taken to measure radioactivity on days 1, 2 or 3, 4 or 5, 6 or 7 and 14 (plus or minus 2), and days 1, 2 or 3, 4 or 5, 6 or 7 and 14 (plus or minus 2), 21 (plus or minus 2), and 28 (plus or minus two) to measure the PEG-AVP0458 protein.
Secondary outcome [3] 298474 0
Immunogenicity of the investigational agent will also be examined.
Timepoint [3] 298474 0
To evaluate the way the immune system responds to the drug, blood samples will be drawn on Day 0, day 6 or 7, day 14 (plus or minus 2), day 21 (plus or minus 2), and day 28 (plus or minus 2).

Eligibility
Key inclusion criteria
Participants will be considered eligible for enrolment in the study if they meet all of the following criteria: Ovarian cancer -Patients with relapsed or refractory ovarian cancer -TAG-72-positive tumours -Detectable disease deemed likely to be assessable by PET by nuclear medicine physician as seen on imaging performed within 21 days of enrolling in the study -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 -Expected survival of greater than or equal to 3 months -18 years of age or greater -Acceptable blood test results on screening (Platelet count greater than or equal to 100 x 109/L, absolute neutrophil count of greater than or equal to 1.5 x 109/L, Aspartate Aminotransferase (AST) less than or equal to 3x upper limit of normal (ULN), or less than 5x ULN with liver metastases,Total bilirubin less than or equal to 34 micro mol/L, Serum creatinine less than or equal to 160 micro mol/L) -Provision of written informed consent. Prostate cancer -Patients with prostate cancer -TAG-72-positive tumours -Detectable disease deemed likely to be assessable by PET by nuclear medicine physician as seen on imaging performed within 21 days of enrolling in the study -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 -Expected survival of greater than or equal to 3 months -18 years of age or greater -Acceptable blood test results on screening (Platelet count greater than or equal to 100 x 109/L, Absolute neutrophil count greater than or equal to 1.5 x 109/L, AST less than or equal to 3x ULN, or less than 5x ULN with liver metastases,Total bilirubin less than or equal to 34 micro mol/L, Serum creatinine less than or equal to 160 micro mol/L) -Provision of written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will not be entered in the study for any of the following reasons:

Ovarian Cancer
-Disease-specific exclusions
-Evidence of current complete or partial bowel obstruction
-Need for Intravenous or Total parenteral nutrition (TPN) hydration
-Chemotherapy, immunotherapy, biologic therapy, radiation therapy, or other investigational product within 4 weeks prior to study entry or likely to be required during the 4-week on-study period
-Patients using corticosteroids or immunosuppressive agents: low dose oral corticosteroids for concomitant medical conditions are permitted. Inhaled or topical corticosteroids are permitted.
-Patients with active infections requiring antibiotics, with bleeding disorders or with other serious illness
-Women who are pregnant (positive hCG test) or lactating
-Women of child-bearing potential who are unwilling to utilize a medically acceptable method of contraception
-Patients with a concurrent active serious medical condition likely to affect participation in the study, such as a documented myocardial infarction less than or equal to 3 months prior to screening or unstable angina pectoris.
-Patients unable to sign informed consent or unwilling to comply with the procedural requirements of this clinical protocol.

Prostate cancer
-Chemotherapy (not including androgen deprivation therapy), immunotherapy, biologic therapy, radiation therapy, or other investigational product within 4 weeks prior to study entry or likely to be required during the 4-week on-study period
-Patients using corticosteroids or immunosuppressive agents: low dose oral corticosteroids for concomitant medical conditions are permitted. Inhaled or topical corticosteroids are permitted.
-Patients with active infections requiring antibiotics, with bleeding disorders or with other serious illness
-Patients with a concurrent active serious medical condition likely to affect participation in the study, such as a documented myocardial infarction less than or equal to 3 months prior or to screening or unstable angina pectoris
-Men who are unwilling to utilize a medically acceptable method of contraception
-Patients unable to sign informed consent or unwilling to comply with the procedural requirements of this clinical protocol.

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)
Eligible patients with ovarian or prostate cancer will be entered into the first dose group, receiving 1 mg/m2 124I-PEG-AVP0458. Three patients will be entered into the first dose group.
If no patients entered in the 1st dose group experience a dose-limiting toxicity (DLT), then an additional three patients may enter the second dose group (10 mg/m2 124I-PEG-AVP0458) 30 days after the last patient on the previous dose group has received the 124I-PEG-AVP0458 infusion.
If any one patient in either cohort of 3 patients experiences a DLT, then 3 additional patients will be entered in that dose group.
If additional patients are treated in the first dose group, all patients entered must have been observed for 30 days before a new patient may receive an infusion in the second dose group. If greater than or equal to two DLTs are observed at a dose, then the maximum tolerated dose is considered to have been exceeded.
In the event 2 or more patients experience DLT at the first dose level, an additional 3 patients will be entered at a 0.5mg/m2 dose level
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Interim analysis will evaluate safety and imaging data available after the dose escalation part of the study and will determine which of the two doses be administered to a final 6 patients in the study
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/03/2012
Actual
29/08/2012
Date of last participant enrolment
Anticipated
Actual
28/02/2015
Date of last data collection
Anticipated
Actual
28/03/2015
Sample size
Target
12
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 440 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [2] 441 0
Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 285670 0
Commercial sector/Industry
Name [1] 285670 0
Avipep Pty Ltd
Country [1] 285670 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Avipep Pty Ltd
Address
343 Royal Parade
Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 284501 0
None
Name [1] 284501 0
Address [1] 284501 0
Country [1] 284501 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287653 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 287653 0
Peter MacCallum Cancer Centre
Level 4, 10 St Andrews Place
East Melbourne, VIC 3002
Ethics committee country [1] 287653 0
Australia
Date submitted for ethics approval [1] 287653 0
Approval date [1] 287653 0
08/02/2012
Ethics approval number [1] 287653 0

Summary
Brief summary
This is a Phase I, open-label study of the safety and biodistribution of two escalating doses of PEG-AVP0458, labeled with 3-5 mCi of 124I for PET imaging. This is the first study of PEG-AVP0458 in humans. PEG-AVP0458 is an experimental molecule, meaning that it is not approved for use in Australia or other parts of the world outside of this trial. The ultimate purpose of this research is to find better ways to detect and treat prostate and ovarian cancers. The product under investigation, PEG-AVP0458, has been designed to attach to a specific protein called TAG-72, which is found on the surface of some types of cancer cells however it is not a treatment for cancer. The aims of this study are to determine the safety of PEG-AVP0458 at the doses studied, and to demonstrate that PEG-AVP0458 can attach to the TAG-72 protein on prostate and ovarian cancer cells in humans. To enter the study patients with prostate or ovarian cancer need to screen as positive for TAG-72 and have disease deemed likely to be assessable by PET scan. An ECOG performance status of 0-1 and an expected survival of at least 3 months are also requirements for study entry. At screening participants must be of at least 18 years of age, provide informed consent to participate and show appropriate blood parameters. Patients with ovarian or prostate cancer are ineligible to participate if any of the exclusion criteria noted in the exclusion criteria section above. Trial Details PEG-AVP0458 will be combined with a low dose radioactive iodine particle by a process called radiolabelling, and injected. The radiolabel acts as a tracer, which means that it can be detected in tissue by a special scanning system called a PET scan. This study is designed to assess the safety and targeting ability of PEG-AVP0458, and no direct therapeutic benefit from the infusion of PEG-AVP0458 is anticipated. The first group of 3 participants enrolled will be allocated to the 1mg/m2 dose group. If any Dose Limiting Toxicities (DLTs) are seen for these 3 participants, the second group of 3 participants will also receive 1mg/m2. If no DLTs are seen in the first group of 3, the second group of 3 participants will receive the 10mg/m2 dose. If any DLTs are seen for these 3 participants, the third group of 3 participants will also receive 10mg/m2. If no DLTs are seen in the second group of 3, the third group of 3 participants (alongside a further 3 participants, total of 6) will receive either the 1mg/m2 or 10mg/m2 dose level, as determined by the outcome of the interim analysis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34452 0
Prof Andrew Scott
Address 34452 0
Director, Centre for PET, Austin Hospital,
Studley Rd, Heidelberg, Vic. 3084
Country 34452 0
Australia
Phone 34452 0
-
Fax 34452 0
Email 34452 0
-
Contact person for public queries
Name 17699 0
Peter Hudson
Address 17699 0
Avipep Pty Ltd
343 Royal Parade
Parkville VIC 3052
Country 17699 0
Australia
Phone 17699 0
+61 3 9349 0301
Fax 17699 0
Email 17699 0
[email protected]
Contact person for scientific queries
Name 8627 0
Peter Hudson
Address 8627 0
Avipep Pty Ltd
343 Royal Parade
Parkville VIC 3052
Country 8627 0
Australia
Phone 8627 0
+61 3 9349 0302
Fax 8627 0
Email 8627 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
This study closed in 2015


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1280Study protocol    362774-(Uploaded-04-02-2019-13-56-08)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 362774-(Uploaded-04-02-2019-13-58-42)-Basic results summary.pdf
Plain language summaryNo See attached abstract. The engineered antibody PEG... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseFirst clinical study of a pegylated diabody 124I-labeled PEG-AVP0458 in patients with tumor-associated glycoprotein 72 positive cancers.2020https://dx.doi.org/10.7150/thno.49422
N.B. These documents automatically identified may not have been verified by the study sponsor.