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Trial registered on ANZCTR


Registration number
ACTRN12618001112257
Ethics application status
Approved
Date submitted
19/06/2018
Date registered
5/07/2018
Date last updated
2/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A long term follow up study of ATX-101 given by intravenous infusion once every week in patients with advanced solid tumours.
Scientific title
A long term follow up study, to evaluate the long term safety and efficacy, of single agent ATX-101 given by intravenous infusion once every week in patients with advanced solid tumours
Secondary ID [1] 295170 0
AM ATX101-02
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12618001070224p - This record is a pre-ceding dose escalation study to determine the highest tolerated dose for this study.

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 308295 0
Condition category
Condition code
Cancer 307302 307302 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ATX-101 treatment will be administered weekly in cycles of 21-day duration, with a single IV
infusion. All subjects will receive mandated premedication with a corticosteroid, and H1 and H2 inhibitors 30 to 60 minutes prior to every dose of ATX-101 as follows:
• Dexamethasone 12 mg orally (or pharmacologically equivalent corticosteroid)
• Loratidine/Cetrizine 10 mg orally (or pharmacologically equivalent H1 inhibitor)
• Ranitidine 300 mg orally (or pharmacologically equivalent H2 inhibitor)
Dosing to occur on Day 1, 8 and 15 (± 3 days) of each cycle for up to 12 months. treatment with ATX-101 the subject will be allowed to escalate to the highest tolerated ATX-101 dose level determined from the AM ATX101-01 study.
Subjects will receive 4 cycles of treatment (i.e. 4 x 21 days = 3 months), then, at the completion of each 4 cycles of treatment (i.e. every 3 months ± 14 days), in addition to all other specified safety evaluations, radiographic (MRI/CT) assessments will be conducted per RECIST V1.1 to evaluate the subject’s ongoing response to long-term treatment, disease status and to determine if dosing per individual subject should continue for the next 4 cycles of treatment, up to a maximum total of 12 months treatment.
Treatment exposure, including duration of treatment and extent of exposure to study drug, will be summarised, for all subjects overall. Total treatment exposure across both AM ATX101-01 and the long term follow up component (AM ATX101-02) will be assessed.
Intervention code [1] 301507 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306261 0
To evaluate the long term safety of weekly intravenous infusions for a further maximum period of 12 months in subjects with advanced solid tumours who have completed participation in study AM ATX101-02 with no progressive disease at the end of End of Study Visit. The following assessments will be used for this evaluation:
- Treatment exposure
- Vital signs and ECG
- Laboratory parameters (haematology and biochemistry)
- Urinalysis
- Physical Examination
- Concomitant Medication review
- Adverse Events (frequency, severity, and duration of treatment-emergent adverse events (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03)


Timepoint [1] 306261 0
Weekly from Baseline (week 1) to Final Follow-Up Visit which should occur 1 week (± 3 days) after the last administered dose of study drug (maximum period of 12 months).
Secondary outcome [1] 348000 0
Composite outcome to evaluate the maintenance of non-progressive disease status by radiographic (MRI/CT) assessments per RECIST V1.1 after a further maximum ATX-101 treatment period of up to 12 months with determination of:
- Progression-free survival (PFS)
- Time to progression (TTP)
Timepoint [1] 348000 0
At the completion of each 4 cycles of treatment i.e. every 3 months (± 14 days) up to a total of 12 months of treatment.
Secondary outcome [2] 348460 0
Exploratory plasma biomarker analysis will be conducted as an exploratory pending the availability of qualified/validated assays. Results from the analysis of exploratory biomarker assessment will be reported separately to the final study report.
Timepoint [2] 348460 0
Following the first administration of ATX-101 in Cycle 1 of treatment and then again at the completion of each 4 cycles of treatment (i.e. every 3 months ± 3 days) for a maximum period of 12 months of treatment.

Eligibility
Key inclusion criteria
1. Subjects with advanced solid tumours who have completed at least six infusions of ATX-101 in study AM ATX101-01 with no progressive disease based on RECIST V1.1 at the AM ATX101-01 EOS visit.
2. Signed written informed consent.
3. Women of child-bearing potential (WOCBP) must use highly effective contraceptive measures (failure rate of < 1% per year when used consistently and correctly) and intend to continue use of contraception for at least 1 month following the last infusion. Highly effective contraceptive measures could include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomized partner, and sexual abstinence
4. Males who are not surgically sterile must use a condom through to study completion and for 30 days after the last treatment administration, unless they have a female partner who is surgically sterile or post-menopausal. They must refrain from fathering a child during this time.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Evidence of disease progression according to RECIST V1.1 during AM ATX101-01.
2. Concurrent anticancer treatment (e.g., cytoreductive therapy, radiotherapy except for palliative bone-directed radiotherapy, immune therapy, or cytokine therapy except for erythropoietin) within 21 days or 5x (five times) their half-lives (whichever is shorter) before the first dose of trial treatment.
3. Use of hormonal agents within 7 days before start of trial treatment, except for subjects with castration-resistant prostate cancer (CRPC), who may remain on treatment with luteinizing hormone–releasing hormone agonists or antagonists.
a. Note: Subjects receiving bisphosphonate or denosumab are eligible provided that treatment was initiated more or equal to 14 days before first dose of treatment.
4. Anticipated requirement for surgery or initiation of anti-cancer therapy during the study period.
5. Breastfeeding or pregnant as confirmed by a positive serum beta human chorionic gonadotropin (ß-HCG) pregnancy test at screening or at subsequent clinic visits.
6. Unwilling or unable to follow protocol requirements.
7. Inadequate venous access to allow collection of blood samples.

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
The total sample size is expected to be up to 36 subjects. No sample size calculation was
performed.
Data will be summarised using descriptive statistics (continuous data) and/or frequency
tabulations with counts and percentages (categorical data) for demographic and baseline
characteristics, efficacy measurements, safety measurements, and all relevant PK measurements.
Details of the statistical analysis, analysis populations, and data reporting will be provided in the Statistical Analysis Plan (SAP) to be finalised prior to database lock.

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)
NSW,SA,WA
Recruitment hospital [1] 11125 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [2] 11126 0
Linear Clinical Research - Nedlands
Recruitment hospital [3] 11127 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 22941 0
5000 - Adelaide
Recruitment postcode(s) [2] 22942 0
6009 - Nedlands
Recruitment postcode(s) [3] 22943 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 299757 0
Commercial sector/Industry
Name [1] 299757 0
Therapim Pty Ltd
Address [1] 299757 0
Shop 3, 2190 Gold Coast Highway Miami, QLD, 4220
Country [1] 299757 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Therapim Pty Ltd
Address
Shop 3, 2190 Gold Coast Highway Miami, QLD, 4220
Country
Australia
Secondary sponsor category [1] 299098 0
None
Name [1] 299098 0
Address [1] 299098 0
Country [1] 299098 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300647 0
Bellberry Human Research Ethics Committee H [EC00459)
Ethics committee address [1] 300647 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 300647 0
Australia
Date submitted for ethics approval [1] 300647 0
23/05/2018
Approval date [1] 300647 0
09/07/2018
Ethics approval number [1] 300647 0

Summary
Brief summary
This is a Phase I, open-label, single arm, long term follow up study to assess safety of ATX-101 in subjects with advanced solid tumours over a maximum period of 12 months.

Who is it for?
You may be eligible to join this study if you have completed participation in the preceding study AM ATX101-01.

Study details
The study is designed to systematically assess safety and tolerability of an additional 12 months of treatment with ATX-101, and to further investigate the exploratory pharmacodynamics (PD; biomarker analyses) and preliminary efficacy of ATX-101 (anti-tumour activity and maintenance of non-progressive disease status).

Willing subjects must provide voluntary written informed consent prior to undergoing any further procedures to determine study eligibility. Screening evaluations will ensure that potential study subjects fulfil all requirements for entry into the long term follow up study. Up to 36 study subjects who have been exposed to ATX-101 in AM ATX101-01 will be enrolled.

ATX-101 treatment will be administered weekly in cycles of 21-day duration, with a single IV infusion of ATX-101 on Day 1, 8 and 15 (± 3 days) of each cycle for up to 12 months, unless criteria for early termination is met. Prior to each infusion subjects will receive mandated premedication with corticosteroid and H1 and H2 inhibitors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84334 0
Dr Michael Millward
Address 84334 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands WA 6009
Country 84334 0
Australia
Phone 84334 0
+61 1300 546 327
Fax 84334 0
Email 84334 0
contactus@linear.org.au
Contact person for public queries
Name 84335 0
Dr Michael Millward
Address 84335 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands WA 6009
Country 84335 0
Australia
Phone 84335 0
+61 1300 546 327
Fax 84335 0
Email 84335 0
contactus@linear.org.au
Contact person for scientific queries
Name 84336 0
Dr Michael Millward
Address 84336 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands WA 6009
Country 84336 0
Australia
Phone 84336 0
+61 1300 546 327
Fax 84336 0
Email 84336 0
contactus@linear.org.au

No information has been provided regarding IPD availability
Summary results
No Results