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Trial registered on ANZCTR


Registration number
ACTRN12620000622909
Ethics application status
Approved
Date submitted
23/04/2020
Date registered
29/05/2020
Date last updated
29/05/2020
Date data sharing statement initially provided
29/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
This trial is a phase 1, single-centre, open label, single-dose study of 89Zr-APOMAB using PET/CT imaging in a series of 18 participants who are known to have inoperable stage III or stage IV non-small cell lung cancer (NSCLC), or limited or extensive stage small cell lung cancer (SCLC), or FIGO stage IV grade 3 serous papillary Ovarian Cancer.
Scientific title
A Phase 1, Single-Centre, Non-Randomised, Open-Labelled, 2-Arm, Single Dose study of Chimeric Anti-La/SSB Antibody (APOMAB) Conjugated with 89Zirconium-Label (89Zr-APOMAB) as a Theranostic Imaging Agent Using ImmunoPET/CT in Patients with Advanced Lung or Ovarian Cancer
Secondary ID [1] 301106 0
APOMAB
Universal Trial Number (UTN)
Trial acronym
APOMAB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Lung Cancer 317197 0
Advanced Ovarian Cancer 317198 0
Condition category
Condition code
Cancer 315337 315337 0 0
Lung - Non small cell
Cancer 315338 315338 0 0
Ovarian and primary peritoneal
Cancer 315339 315339 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Theranostic Interventions:
Single dose of 37MBq of 89Zr-APOMAB will be given intravenously to each patient participating in the study:
1. Patients participating in Stage 1 (untreated population - in the first stage, the untreated groups of patients will have completed the post-antibody imaging at completion of this study before commencing any chemotherapy, planned or unplanned. These patients will not participate in the second stage of the study): On day of study drug (APOMAB) injection (Study Day 1)
2. For patients enrolled in Stage 2 (treated population - this group of patients will have initiated a first cycle of first-line platinum based chemotherapy before antibody injection. Again, patients will have completed the post-antibody imaging at completion of this study before commencing the second cycle of chemotherapy): 89Zr-APOMAB to be given on Day 1, which is the day after Cycle 1 Day 8 (i.e. C1D9) of platinum based chemotherapy (PBCT).
APOMAB and 89Zr-APOMAB are both names used for the same formulation within this protocol.
Patients will be consented, screened & deemed to be eligible to participate in study, 89Zr-APOMAB will be administered and images collected, safety reviews and follow-ups will be scheduled. Patients will still receive routine care for their standard of care chemotherapy treatment where planned.
An imaging manual will be followed for each dosing and image collection procedure. Each study participants study procedures will be documented and a record will be kept within our RAH Cancer Clinical Trials Unit.
Intervention code [1] 317416 0
Diagnosis / Prognosis
Comparator / control treatment
there is only one dose of 89Zr-APOMAB being used, there are however 2 groups of patients as described above and their results will be compared
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323590 0
Evaluate the safety and tolerability of 89Zr-APOMAB following intravenous administration, by monitoring for frequency of occurrence and severity of abnormal findings in safety investigations: eg. physical examinations, vital signs, ECG, clinical laboratory results, monitoring adverse events & concomitant medications
Timepoint [1] 323590 0
Day 13 following administration of 89Zr-APOMAB
Secondary outcome [1] 382295 0
1. Determine the whole-body radiation dosimetry of 89Zr-APOMAB in study participant
Timepoint [1] 382295 0
Post imaging on Day 1, Day 2, Day 4, Day 8, & Day 11-13 at end of study
Secondary outcome [2] 382668 0
Assess diagnostic image quality of 89Zr-APOMAB using a time-of-flight PET (TOF-PET) compared to conventional PET (C-PET reconstruction)
Timepoint [2] 382668 0
Post imaging on Day 1, Day 2, Day 4, Day 8, & Day 11-13 at end of study
Secondary outcome [3] 382673 0
Assess diagnostic image quality of 89Zr-APOMAB using a 37MBq (1mCi) activity dose and different acquisition durations (5, 10, 15 vs 20 min.), this will be assessed by reviewing the medical images collected
Timepoint [3] 382673 0
Post imaging on Day 1, Day 2, Day 4, Day 8, & Day 11-13 at end of study
Secondary outcome [4] 382674 0
Establish activity dose and recommended acquisition modalities for further clinical development, this will be achieved by reviewing images collected and patient medical records
Timepoint [4] 382674 0
at end of study when all data is collected and reviewed
Secondary outcome [5] 382675 0
Investigate the pharmacokinetics and serum stability of 89Zr-APOMAB in both treated and untreated patients and comparing results, radioactivity levels and blood clearance rates will also be measured using blood and urine sampling at different time points post-administration
Timepoint [5] 382675 0
Post imaging on Day 1, Day 2, Day 4, Day 8, & Day 11-13 at end of study
Secondary outcome [6] 382676 0
Evaluate the immunogenicity of 89Zr-APOMAB by determining the incidence of human anti-chimeric antibodies (HACA), by analysing patients blood samples collected at different study timepoints
Timepoint [6] 382676 0
Post imaging on Day 1, Day 2, Day 4, Day 8, & Day 11-13 at end of study

Eligibility
Key inclusion criteria
Participants are eligible if they meet all of the following inclusion criteria:
1. Signed informed consent
2. Age greater than or equal to18 years
3. ECOG performance status 0-1
4. Life expectancy of greater than or equal to12 weeks
5. Histologically confirmed, inoperable stage III or IV non-small cell lung cancer (NSCLC) or limited or extensive stage small cell lung cancer (SCLC) suitable for palliative platinum-based chemotherapy, OR
6. Histologically confirmed, FIGO stage III or IV high-grade serous ovarian cancer (HGSOC) suitable for palliative or neoadjuvant platinum-based doublet chemotherapy
7. Must have sufficient tumour tissue available for assessment of homologous recombination deficiency (HRD). If not, a fresh tumour biopsy may be required
8. At least one area of disease measurable by RECIST v1.1 on CT or MRI at baseline before study entry
9. Adequate liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
• Estimated glomerular filtration rate (eGFR) of greater than or equal to 40mL/min as measured using the Cockroft Gault formula
• Total bilirubin less than or equal to 1.5x the upper limit of normal (ULN)
• ALT and AST less than or equal to 2.5x ULN (less than or equal to 5x ULN for participants with liver involvement of their cancer)
10. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to follow any of these measures if not surgically sterile during the course of the trial
• Total abstinence from sexual intercourse
• Double barrier methods (e.g. cervical cap, condom, contraceptive sponge, diaphragm or vaginal ring).
• Intrauterine device
• Contraception is necessary for at least 7 weeks after receiving the study drug
This protocol covers both lung and ovarian cancer populations, however, all patients must meet all of the inclusion criteria listed above if they are to be deemed eligible to participate
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded if they meet any of the following exclusion criteria:
1. Pregnant or breastfeeding females.
2. Participants with prior exposure to any chimeric antibodies and mouse proteins will be excluded.
3. Known uncontrolled hyperthyroidism
4. Exposure to any experimental diagnostic or therapeutic drug within 30 days from the date of planned administration of 89Zr-APOMAB
5. Exposure to any radiopharmaceutical within 30 days before the administration of 89Zr-APOMAB.
6. Diagnosis of systemic lupus erythematosis or Sjögren Syndrome or presence of antinuclear antigen (ANA) titre of = 1:160 or extractable nuclear antigen (ENA) antibodies
7. Women (with or without a systemic autoimmune disease) who have a history of giving birth to a child with congenital heart block
8. Grade = 2nd degree atrioventricular block on ECG
9. Psychiatric illness or social situations that could limit compliance to the study requirements
10. Participants unwilling or unable to provide written informed consent
11. In the opinion of the investigator, the participant is not suitable to receive 89Zr-APOMAB

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
non-randomised, open-label, 2 stage, 1 dose investigation per stage
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Statistical analyses will be performed after database lock, after all study data including the end-of-study visit have been collected and cleaned.
The statistical analyses in this study will primarily be descriptive.
Descriptive analyses will include:
• Mean, standard derivation, median and range for continuous variables,
• Median, range and frequency distribution for discrete (ordinal) variables,
• Frequency distribution for nominal variables
Analyses of PET parameters will be calculated according to acquisition condition group.
Details on statistical analyses for safety, dosimetry and diagnostic efficacy will be provided in the Statistical Analysis Plan (SAP), which will be prepared during the study. The SAP will describe in detail the analysis of adverse effects, the analysis of laboratory data, the analysis of vital signs, the analysis of dosimetry data, and the comparative analysis for diagnostic images. It will address matters such as observational period for adverse effects, rules for counting of multiple adverse effects related to a single participant and recording adverse effects with unknown grade.

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)
SA
Recruitment hospital [1] 16541 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 30103 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 305551 0
Commercial sector/Industry
Name [1] 305551 0
AusHealth research
Address [1] 305551 0
65 Hardys Road, Underdale, SA. 5032
Country [1] 305551 0
Australia
Primary sponsor type
Government body
Name
Central Adelaide Local Health Network
Address
Royal Adelaide Hospital, Port Road, Adelaide. SA. 5000
Country
Australia
Secondary sponsor category [1] 305957 0
None
Name [1] 305957 0
Address [1] 305957 0
Country [1] 305957 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305856 0
Central Adelaide Local Health Network
Ethics committee address [1] 305856 0
Level 3, Roma Mitchell House, North Tce, Adelaide, SA, 5000.
Ethics committee country [1] 305856 0
Australia
Date submitted for ethics approval [1] 305856 0
05/12/2019
Approval date [1] 305856 0
07/04/2020
Ethics approval number [1] 305856 0
R20191112

Summary
Brief summary
The purpose of this study is to determine if APOMAB, (an imaging agent which is an antibody with a small amount of radiation attached to it) which has been designed to detect tumour cell death, is safe and tolerable to use in humans.
The APOMAB trial will be done in two stages. In the first stage of the trial in 6 participants, you will receive the APOMAB injection if you have an advanced lung or ovarian cancer but only if you are not receiving any chemotherapy at the time that the APOMAB injection is planned. In the second stage of the trial in 12 participants, you will receive the APOMAB injection after the first cycle of standard chemotherapy for your advanced lung or ovarian cancer.
If you are an adult, have received a new diagnosis of advanced lung or ovarian cancer, and you have either commenced or are about to commence platinum based chemotherapy, then you may be asked to consider participating in this study, and if you agree, then you will be asked to sign a consent form.
There are a number of tests and procedures which need to be carried out to determine if you would be eligible to take part in this study. This is called the 'screening period', and can take up to 14 days to complete. During this period you will be reviewed by a doctor who will take a full medical history, perform a physical exam, an ECG ( a non-invasive test of the electrical activity of your heart), routine blood tests, collection of small amount of blood for study purposes, a FDG-PET/CT scan if this has not been recently performed, once all test results have been reviewed and the study doctor confirms that you are eligible for the study, a date will be organised for you to receive an injection of the study drug APOMAB.
Prior to the injection, the study doctor will review you again, you will remain at the imaging centre for approximately 4-5 hours post injection, as a number of scans will be collected as well as blood and urine samples on this day. You will be required to undergo further medical reviews and scans, with further blood and urine samples to be collected on Days 2, 4, 8 & 13 post injection. No other visits will be required for study purposes. You will then either commence or continue your standard chemotherapy treatment.
The results of this study will help further the development of immunoPET/CT with APOMAB. We are aiming to find out whether an early indication of tumour cell death on APOMAB immunoPET/CT scans before a patient has a second cycle of chemotherapy increases the likelihood that tumours in the body shrink. Having this information sooner in the treatment course may allow future cancer patients to know that effective treatment can continue even in spite of side effects. Also future cancer patients can know that ineffective treatment can be discontinued, thus avoiding side effects without any prospect of benefit, and allow these patients to choose an alternative treatment sooner rather than later.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101830 0
Prof Michael P Brown
Address 101830 0
Royal Adelaide Hospital, Level 6E.351, Port Road, Adelaide, SA. 5000
Country 101830 0
Australia
Phone 101830 0
+61 8 70742335
Fax 101830 0
+61 8 70746211
Email 101830 0
michaelp.brown@sa.gov.au
Contact person for public queries
Name 101831 0
Mrs Anne Milton
Address 101831 0
Royal Adelaide Hospital, Level 6E.351, Port Road, Adelaide, SA. 5000
Country 101831 0
Australia
Phone 101831 0
+61 70742342
Fax 101831 0
+61 8 70746211
Email 101831 0
anne.milton@sa.gov.au
Contact person for scientific queries
Name 101832 0
Prof Michael P Brown
Address 101832 0
Royal Adelaide Hospital, Level 6E.351, Port Road, Adelaide, SA. 5000
Country 101832 0
Australia
Phone 101832 0
+61 8 70742335
Fax 101832 0
+61 8 70746211
Email 101832 0
michaelp.brown@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This has yet to be decided
What supporting documents are/will be available?
No other documents available
Summary results
No Results