Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000689471
Ethics application status
Approved
Date submitted
6/05/2016
Date registered
26/05/2016
Date last updated
19/03/2020
Date data sharing statement initially provided
19/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of IMP4297 in Patients with Advanced Solid Tumors
Scientific title
A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of IMP4297 in Patients with Advanced Solid Tumors
Secondary ID [1] 289147 0
IMP4297-2016-AU01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced solid tumours 298661 0
Condition category
Condition code
Cancer 298722 298722 0 0
Breast
Cancer 298723 298723 0 0
Ovarian and primary peritoneal
Cancer 298724 298724 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase 1, First-In-Human, open label study, trialing a new PARP inhibitor medication IMP4297 in participants with advanced solid tumour.
Six different dosage cohorts 2mg, 6mg, 10mg, 20mg, 30mg and 40mg will be used to establish the maximum tolerated dosage. First participant in each dosing cohort will be administered one dose of IMP4297 capsule, followed by a wash out period of at least 5 half-lives or 7 days. Safety information such as pathology result or adverse events experienced will be collected following first dosing. This will be reviewed by the a safety review committee that is made up of the Principal Investigator, Medical Monitor, the study Sponsor and a representative from the Clinical Research Organisation, which will collectively determine if it is safe to proceed to continue with the next scheduled dosing cohort. Participant will proceed with repeat once daily dose at the same dose level for 3 weeks. Each repeat dose treatment cycle will be composed of 3 weeks (Day 1 to Day 21). IMP4297 will be administered by participants at home. Participants will be instructed to bring unused IMP4297 capsules with them to each visit for trial staff to review and confirm amount of IMP4297capsules taken since the last visit. The administration of the IMP4297 capsules will be recorded. Study drug compliance will be assessed using these records in conjunction with a count of unused IMP4297 capsules. Participants who are benefiting from IMP4297 may have the possibility of treatment beyond 1 year at the investigator's discretion. Participants who experience disease progression or unacceptable side effects, are not compliant with study protocol or in the opinion of the investigator will have IMP4297 administration discontinued and study participation will be terminated.
Intervention code [1] 294664 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298201 0
To evaluate the safety and tolerability of single and multiple doses of IMP4297 administered to participants with advanced solid tumors. This is assessed by the participating investigator through the results of ECG monitoring, pathology blood collection, vital sign monitoring and recording of adverse events in accordance to CTCAE version 4.03.
Timepoint [1] 298201 0
Safety and tolerability will be assessed and reviewed prior to opening the next cohort of dose escalation. This is assessed by ECG and vital sign monitoring, adverse event recording and pathology blood collection on Single dose Day 1, Cycle 1 Day 1, Day 8, Day 15 of each cohort. This will be reviewed at prior to each dosing cohort by the Safety review committee to assess the incidences, natures relatedness and severity of adverse events, changes in vital signs, changes in pathology blood tests, changes in ECG, changes in physical examination, changes in ECOG. Dose escalation and opening of the next cohort will occur only after acceptable tolerability has been demonstrated throughout the entire Cycle 1. Participants may be required to stay overnight in hospital for observation of any side effects following first dose of each single dosing cohort.
Primary outcome [2] 298202 0
The second composite primary endpoint for the study is to determine the maximum tolerated dose (MTD) and to evaluate the dose limiting toxicities (DLTs) of IMP4297. The Safety review committee will assess the incidences, natures relatedness and severity of adverse events, changes in vital signs, changes in pathology blood tests, changes in ECG, changes in physical examination, changes in ECOG at each DLT assessment window (Single dose and Cycle 1 Day 1 to 21). Dose escalation and opening of the next cohort will occur only after acceptable tolerability has been demonstrated throughout the entire Cycle 1.
Timepoint [2] 298202 0
Safety and tolerability will be assessed and reviewed prior to opening the next cohort of dose escalation
Secondary outcome [1] 323480 0
To characterize the pharmacokinetics (PK) of a single and multiple doses of IMP4297 in participants with advanced solid tumour
Timepoint [1] 323480 0
Pharmacokinetic (PK) pathology blood collection will be performed for every cohort during single dosing, Cycle 1 and Cycle 2.
At single dosing cohort, PK pathology bloods will be collects pre dose dosing and post dosing at time points: 15 min, 30 min, 60 min, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 30 hours and 48 hours.
At Cycle 1, PK pathology bloods will be collects pre dose dosing on Day 1, Day 2, Day 8, Day 15, Day 16 and Day 21. Post dose PK pathology blood collections will be performed on Day 1, 15 and 21 at time points: 30 min, 2 hours, 4 hours, 6 hours and 8 hours.
Pre dosing PK pathology blood collection will be collected on Cycle 2 Day 1.

Eligibility
Key inclusion criteria
1. Signed Informed Consent Form
2. Age greater than or equal to 18 years
3. Histologically or cytologically documented, incurable, advanced solid malignancy that has progressed on, or failed to respond to, at least one prior systemic therapy
4. Evaluable or measurable disease per RECIST 1.1
5. ECOG performance status of 0 or 1
6. In the dose expansion stage, patients with BRCA mutation will be enrolled. Patients with breast cancer, ovarian cancer and prostate cancer are preferred.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inadequate haematologic and organ function, defined by the following (haematologic parameters must be assessed greater than or equal to 14 days after a prior treatment, if any):
a. Absolute neutrophil count <1500 cells/uL
b. Haemoglobin <9 g/dL
c. Total bilirubin >1.5 x the ULN, with documented liver metastases total bilirubin >3 x the ULN .
d. AST and/or ALT >2.5 x the ULN, with documented liver metastases AST and/or ALT levels > 5 x the ULN.
e. Serum creatinine > 1.5 x the ULN, or creatinine clearance < 50 mL/min based on a documented 24-hour urine collection.
f. International normalized ratio (INR) > 1.5 x the ULN or activated partial thromboplastin time (aPTT) >1.5 x the ULN
The INR applies only to patients who do not receive therapeutic anti-coagulation.
2. Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, radiotherapy within 4 weeks prior to initiation of study treatment with the following exceptions:
a. Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists for prostate cancer
b. Hormone-replacement therapy or oral contraceptives
c. Palliative radiation to bone metastases > 2 weeks prior to Day 1
3. Adverse events from prior anti-cancer therapy that have not resolved to CTCAE Grade less than or equal to 1, except for alopecia
4. Clinical significant active infection
5. Known clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
6. Known human immunodeficiency virus infection
7. New York Heart Association (NYHA) Class II or greater congestive heart failure; history of myocardial infarction or unstable angina within 6 months prior to Day 1; history of stroke or transient ischemic attack within 6 months prior to Day 1
8. Active or untreated brain metastasis
9. Pregnant (positive pregnancy test) or lactating women
10. Male or female patients of child-producing potential unwilling to use double barrier contraception: condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD), contraceptives (oral, injectable or parenteral), implanon, or other avoidance of pregnancy measures during the study and for 90 days after the last day of treatment
11. Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
12. Inability to comply with study and follow-up procedures
13. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications.

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



Intervention assignment
Other
Other design features
There are 6 cohorts in which participants will be enrolled in with the following IMP4297 dosage levels planned. Opening of the next cohort will occur only after acceptable tolerability has been demonstrated throughout the entire Cycle 1 observation window as determined by the safety review committee:
Cohort 1- 2mg
Cohort 2- 6mg
Cohort 3- 10mg
Cohort 4- 20mg
Cohort 5- 30mg
Cohort 6- 40mg
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/07/2016
Actual
3/02/2017
Date of last participant enrolment
Anticipated
31/03/2020
Actual
Date of last data collection
Anticipated
31/03/2021
Actual
Sample size
Target
30
Accrual to date
11
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 7438 0
St George Private Hospital - Kogarah
Recruitment hospital [2] 10218 0
Nucleus Network - Melbourne
Recruitment hospital [3] 16143 0
Blacktown Hospital - Blacktown
Recruitment postcode(s) [1] 15249 0
2217 - Kogarah
Recruitment postcode(s) [2] 21747 0
3004 - Melbourne
Recruitment postcode(s) [3] 29672 0
2148 - Blacktown

Funding & Sponsors
Funding source category [1] 293524 0
Commercial sector/Industry
Name [1] 293524 0
IMPACT Therapeutics, Inc
Country [1] 293524 0
China
Primary sponsor type
Commercial sector/Industry
Name
IMPACT Therapeutics Australia Pty Ltd
Address
Level 29 , 525 Collins Street
Melbourne, VIC, 3000
Country
Australia
Secondary sponsor category [1] 292344 0
None
Name [1] 292344 0
None
Address [1] 292344 0
None
Country [1] 292344 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296847 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 296847 0
129 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 296847 0
Australia
Date submitted for ethics approval [1] 296847 0
14/09/2016
Approval date [1] 296847 0
21/09/2016
Ethics approval number [1] 296847 0
Ethics committee name [2] 299741 0
The Alfred HREC
Ethics committee address [2] 299741 0
55 Commercial Road, Melbourne VIC 3004
Ethics committee country [2] 299741 0
Australia
Date submitted for ethics approval [2] 299741 0
12/05/2017
Approval date [2] 299741 0
01/09/2017
Ethics approval number [2] 299741 0

Summary
Brief summary
Study details:
This clinical trial aims to establish the safety and tolerability profile of the drug IMP4297, to determine the maximum tolerated dose (MTD) of IMP4297, and to evaluate the dose limiting toxicities (DLT) of IMP4297 in study participants with advanced solid malignancy that has progressed on, or failed to respond to, at least one prior systemic therapy. The secondary purposes of this trial are to assess the distribution of IMP4297 at various time points (pharmacokinetics) and to also obtain preliminary information on the antitumour activity of IMP4297.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have histologically or cytologically documented, incurable, advanced solid malignancy that has progressed on, or failed to respond to, at least one prior systemic therapy. Patients with breast cancer, ovarian cancer and prostate cancer are preferred. Study details Participants in this trial will initially receive a single dose of the drug IMP4297 to allow an assessment of safety, tolerability and pharmacokinetics (PK). The drug is administered orally in a tablet form. If tolerated, participants will then proceed one week later to receive a daily dose of IMP4297 for 3 weeks. This treatment cycle will then continue until unacceptable toxicity is indicated, the disease progresses, or the study participant withdraws his/her consent; or the study participant meets any other criteria for withdrawal. Up to 6 dose levels are planned to investigate the maximum tolerated dose (MTD) of IMP4297. This trial employs a stepwise dose escalation scheme which allows the safety and tolerability of each dose level to be evaluated before study participants are exposed to a higher dose level. Participants will be required to give blood samples and undergo regular clinical assessments in order to evaluate treatment safety and tolerability.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65646 0
Prof Jason Lickliter
Address 65646 0
| Nucleus Network Limited, Level 5, Burnet Tower, AMREP Precinct, 89 Commercial Road, Melbourne, Victoria 3004, Australia
Country 65646 0
Australia
Phone 65646 0
+613 9936 8082
Fax 65646 0
Email 65646 0
[email protected]
Contact person for public queries
Name 65647 0
Ms Michelle Lin
Address 65647 0
Syneos Health, 7D, 167 Tun Hwa North Rd. Taipei 10549
Country 65647 0
Taiwan, Province Of China
Phone 65647 0
+886 2 3518 5812
Fax 65647 0
Email 65647 0
[email protected]
Contact person for scientific queries
Name 65648 0
Dr David Fuller
Address 65648 0
Suite 1, Level 2, 924 Pacific Highway, Gordon NSW 2072
Country 65648 0
Australia
Phone 65648 0
+61284379238
Fax 65648 0
Email 65648 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?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7392Study protocol  [email protected]
7393Informed consent form  [email protected]
7394Ethical approval  [email protected]
7395Statistical analysis plan  [email protected]
7396Clinical study report  [email protected]
7397Analytic code  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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