Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001342808
Ethics application status
Approved
Date submitted
18/06/2021
Date registered
7/10/2021
Date last updated
19/11/2023
Date data sharing statement initially provided
7/10/2021
Date results information initially provided
10/02/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Study To Determine The Safety, Tolerability, Pharmacokinetics And Recommended Phase 2 Dose Of CCX559 In patients With Solid Tumors
Scientific title
A Phase 1 First In Human, Multicenter, Open label Study To Determine The Safety, Tolerability, Pharmacokinetics And Recommended Phase 2 Dose Of CCX559 In Subjects With Solid Tumors
Secondary ID [1] 304215 0
CL001_559
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplastic Disorder - Solid Tumors 321912 0
Condition category
Condition code
Cancer 319639 319639 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study drug, CCX559, is a small molecule compound that is a highly potent and selective inhibitor of human programmed death protein-ligand 1 (PD-L1).
The dose range is from 30 mg to 300 mg once daily
CCX559 will be administered Orally in 2 different forms - Powder-in-bottle (Dose Level 1, 2) and Capsule (Dose Level 3, 4, 5, 6)
b. Duration: Doses will be administered once a day on every day 21-day cycles
c. Mode of Administration: CCX559 will be administered Orally in 2 different forms - Capsule and Powder-in-bottle (PIB). Powder-in-bottle form will be mixed with 15ml of room temperature water before oral administration.
d. Blood samples will be collected on pre-determined days of the study and analyzed to assess whether the study drug has been taken.
2. Separate cohorts will be enrolled per dose level. Lower dose levels will receive powder-in-bottle while higher dose levels will receive study drug in capsules
4. Study drug will be administered once a day on every day of 21- day cycle until treatment discontinuation due to dose limiting toxicity, confirmed disease progression, withdrawal of consent, subject being lost to follow-up, death, study termination, or study completion
Intervention code [1] 320589 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327567 0
It is a composite primary outcome and has been updated as below
• Safety evaluated with the severity of adverse events (AEs) and serious adverse events
(SAEs) assessed through CTCAE scale Version 5.0
Timepoint [1] 327567 0
Weekly from baseline through Cycle 1, then bi-weekly from Cycle 2 onward until patient comes off study.
Primary outcome [2] 327568 0
Pharmacokinetic characteristics determined by noncompartmental analysis; these may include, but are not limited, to maximum concentration (Cmax), time to maximum concentration (Tmax), area under the concentration-time curve (AUC), apparent clearance (CL/F), and half-life (t½), etc
Plasma from Blood samples will be used for PK sampling.
Timepoint [2] 327568 0
Blood samples collected at cycle 1 Day 1: Predose, 0.5, 1, 2, 3,4,6 and 8 hrs post-dose;
Day 2, Day 8, Day 15: Predose;
Day 5: Predose (0), 0.5, 1, 2, 3,4 hrs post-dose;
Day 21: Predose (0), 0.5, 1, 2, 3,4, 6 and 8 hrs post-dose.
For cycle 2 and 4 blood samples will be collected at predose on day 1 and day 15
For cycle 3 Day 1: Predose, 0.5, 1, 2, 3,4,6 and 8 hrs post-dose and predose on day 15
Secondary outcome [1] 395681 0
To explore the anti-tumor activity of CCX559 through RECIST (Response Evaluation Criteria in Solid Tumors) and Modified RECIST for immune-based therapeutics (iRECIST)

Subjects will undergo tumor imaging assessments: tumors will be evaluated by CT and/or MRI based on RECISTv1.1 and iRECIST guidelines.
Timepoint [1] 395681 0
Timepoints of secondary outcome :Tumor imaging will be performed at screening and every 6 weeks ±1 week after the first 2 cycles of treatment period (Cycle 3 Day 1 (1 day at day 43), Cycle 5 Day 1 (1 day at day 85), Cycle 7 Day 1 (1 day at day 127) with possible decrease of imaging frequency to every 12 weeks after Cycle 9 Day 1, then at End of treatment (within 7 days after the last dose of study drug) and at Safety Follow up (30 ±7 days following last dose of CCX559

Eligibility
Key inclusion criteria
1. Aged at least 18 years (inclusive at the time of informed consent);
2. ECOG Performance Status of 0 to 1
3. Life expectancy of greater than or equal to 12 weeks.
4. Must not have had a live vaccine administration within 28 days prior to the first dose of study drug.
5.Must have the ability to swallow and retain oral medications
6. Histologically or cytologically confirmed solid tumor that is refractory, locally advanced, or metastatic and for which standard curative or palliative measures do not exist or are no longer effective.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receiving medications that are strong inhibitors or inducers of CYP3A4
2. Receiving drugs that prolong the QTc interval
3. Received anticancer therapy, including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy or investigational device, within 28 days (or 5 half-lives for biologic/non-cytotoxic agents, whichever is shorter), prior to the first dose of the study drug. Palliative radiotherapy given within 28 days prior to the first dose of study drug may be approved on a case-by-case basis in discussion with the Sponsor.
4. Has a history of clinically significant allergic reactions attributed to compounds of similar
chemical composition to CCX559 or other agents used in study.
5. Has an uncontrolled intercurrent illness or clinically significant uncontrolled condition(s);
active bacterial, fungal, or viral infections requiring systemic therapy
6. History of primary immunodeficiency, bone marrow transplantation or solid organ
transplantation

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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Study has been terminated by the sponsor for strategic reasons. No safety concerns.
Date of first participant enrolment
Anticipated
Actual
2/08/2021
Date of last participant enrolment
Anticipated
22/04/2022
Actual
10/10/2022
Date of last data collection
Anticipated
31/07/2023
Actual
7/06/2023
Sample size
Target
90
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA,VIC
Recruitment hospital [1] 19441 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [2] 24029 0
Southside Cancer Care Centre - Miranda
Recruitment hospital [3] 24030 0
Ashford Cancer Centre: Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [4] 24031 0
Peninsula Oncology Centre - Frankston
Recruitment postcode(s) [1] 34023 0
3144 - Malvern
Recruitment postcode(s) [2] 39522 0
2228 - Miranda
Recruitment postcode(s) [3] 39523 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 39524 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 308590 0
Commercial sector/Industry
Name [1] 308590 0
ChemoCentryx, Inc
Country [1] 308590 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
ChemoCentryx, Inc
Address
835 Industrial Rd, Suite 600, San Carlos CA 94070
Country
United States of America
Secondary sponsor category [1] 309460 0
None
Name [1] 309460 0
Address [1] 309460 0
Country [1] 309460 0
Other collaborator category [1] 281783 0
Commercial sector/Industry
Name [1] 281783 0
Novotech (Australia) Pty Limited
Address [1] 281783 0
Level 3, 235 Pyrmont St Pyrmont
NSW 2009
Country [1] 281783 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308526 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 308526 0
123, Glen Osmond Road, Eastwood South Australia, 5063
Ethics committee country [1] 308526 0
Australia
Date submitted for ethics approval [1] 308526 0
14/04/2021
Approval date [1] 308526 0
25/05/2021
Ethics approval number [1] 308526 0

Summary
Brief summary
This study aims to determine the safety, tolerability and pharmacokinetics (drug interactions within the body) of CCX559, a new chemotherapy drug that has not been previously tested in humans.

Who is it for?
You may be eligible for this study if you are aged 18 or older, you have a solid tumour of any cancer that is considered to be refractory (not responding to treatment), or you are intolerant of other approved treatments including standard chemotherapy, radiotherapy, and/or immunotherapy.

Study details
All participants who choose to enrol in this study will be given the study drug (CCX559) in either a powder form or as a capsule to be taken each day for 21 day treatment cycles. During each treatment cycle, participants will also be asked to report any side effects they have experienced and will undergo CT imaging at the beginning of every other treatment cycle (Cycles 3,5,7, 9 etc.), and again at the end of the study (7 days after the last dose) and after the safety follow up visit (30 days after the last dose). After taking the first dose, participants will also be asked to provide several [blood] samples over the first 24 hours, on Days 2, 5, 8, 15, 21 of the first treatment cycle and then again at the start and midpoint of each 21-day treatment cycle for the duration of the study. Overall study participation will take up to 2 years.

It is hoped this research will determine whether CCX559 is safe and can be tolerated by adult cancer patients. If CCX559 is safe, future studies may be conducted to determine the drug's effect on cancer progression, which may improve health outcomes for future cancer patients
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111014 0
Prof Paul De Souza
Address 111014 0
Southside Cancer Care Centre
3/533 Kingsway, Miranda NSW 2228
Country 111014 0
Australia
Phone 111014 0
+61 404003220
Fax 111014 0
Email 111014 0
[email protected]
Contact person for public queries
Name 111015 0
Prof Paul De Souza
Address 111015 0
Southside Cancer Care Centre
3/533 Kingsway, Miranda NSW 2228
Country 111015 0
Australia
Phone 111015 0
+61 404003220
Fax 111015 0
Email 111015 0
[email protected]
Contact person for scientific queries
Name 111016 0
Mr Ramandeep Sharma
Address 111016 0
Novotech (Australia) Pty Limited, PO Box: 244 Pyrmont NSW 2009 | Level 2, 15-31 Pelham Street Carlton VIC 3053 Australia
Country 111016 0
Australia
Phone 111016 0
+61 3 9341 1992
Fax 111016 0
+61 3 9341 1998
Email 111016 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


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
EmbaseCCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity.2023https://dx.doi.org/10.1371/journal.pone.0286724
N.B. These documents automatically identified may not have been verified by the study sponsor.