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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04814875




Registration number
NCT04814875
Ethics application status
Date submitted
4/03/2021
Date registered
24/03/2021
Date last updated
14/02/2024

Titles & IDs
Public title
A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy
Scientific title
Phase 1b/2a Study Investigating ATX-101 in Combination With Platinum-based Chemotherapy in Platinum-sensitive, Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancer
Secondary ID [1] 0 0
AM ATX101-03
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Fallopian Tube Cancer 0 0
Primary Peritoneal Carcinoma 0 0
High Grade Serious or Endometrioid Carcinoma of the Ovary, Fallopian Tube, or Primary Peritoneal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)

Experimental: Part 1 - ACD (Safety) - ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)

Experimental: Part 2 - ACD (Efficacy) - ATX-101 plus carboplatin and pegylated liposomal doxorubicin (ACD)


Treatment: Drugs: ATX-101 + Carboplatin + Pegylated liposomal doxorubicin (ACD)
Pegylated liposomal doxorubicin (30 mg/m²) will be administered intravenously on Day 1 of each 28-day cycle; carboplatin (AUC5) will be administered intravenously on Day 1 of each cycle.
ATX-101 will be administered intravenously on Day 2 of each cycle in three escalation cohorts: 20, 30, and 45 mg/m² according to a 3+3 design.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: To determine the maximum tolerated dose (MTD) of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin. Measured by incidence of Dose Limiting Toxicity.
Timepoint [1] 0 0
Assessed from the time of the first administered dose of ATX-101 up to the last treatment in Cycle 2 (i.e. Days 2 to 30).
Primary outcome [2] 0 0
Part 2: To assess the progression free survival (PFS) of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin. Measured by Tumor assessments.
Timepoint [2] 0 0
Assessed from Day 1 to Week 85
Secondary outcome [1] 0 0
Part 1: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
Timepoint [1] 0 0
Assessed from Day 1 to Week 85
Secondary outcome [2] 0 0
Part 1: To characterize the plasma PK profile of ATX-101 following IV infusion in combination with carboplatin/pegylated liposomal doxorubicin.
Timepoint [2] 0 0
From pre-dose [within 30 min prior to infusion] until 60 min post infusion
Secondary outcome [3] 0 0
Part 2: To assess the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ATX-101 in combination with carboplatin/pegylated liposomal doxorubicin.
Timepoint [3] 0 0
Assessed from Day 1 to Week 85

Eligibility
Key inclusion criteria
1. Women = 18 years of age

2. Is not a woman of childbearing potential:

1. Surgically sterile (i.e., had a bilateral tubal ligation, hysterectomy,
salpingectomy, or bilateral oophorectomy at least 6 months prior to Day 1 of the
study) or;

2. Postmenopausal for at least 1 year prior to Day 1 of the study, and have follicle
stimulating hormone levels in the postmenopausal range for the study site.

3. Signed written informed consent

4. Histologically confirmed high grade serous or endometrioid carcinoma of the ovary,
fallopian tube, or primary peritoneal cancer

5. 1 to 3 prior systemic treatment lines. Prior maintenance therapy with bevacizumab or
PARP inhibitors is permitted.

6. Platinum-sensitive carcinoma, defined as disease progression after = 6 months
following the most recent platinum-based therapy of the disease

7. Measurable disease on CT/MRI scan according to RECIST 1.1

8. ECOG Performance status 0 to 1

9. Life expectancy of at least 6 months

10. Meet the following laboratory requirements:

1. Hemoglobin (HGB) = 100 × 109/L

2. Absolute neutrophil count (ANC) = 1.5 × 109/L

3. Platelet count = 100 × 109/L

4. aPTT/PT = 1.5 x ULN

5. Total bilirubin level = 1.5 × ULN

6. AST and ALT = 2.5 × ULN (= 5 × ULN if liver metastasis present)

7. Creatinine Clearance > 60 mL/min, as calculated by Cockcroft-Gault formula, or
serum creatinine = 1.5 × ULN.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have received an anti-cancer/investigational drug within 4 weeks prior to study drug
administration

2. Have received a vaccine for COVID-19 within 14 days prior to the first dose of ATX-101
or are scheduled/intend to have a COVID-19 vaccine on Day 1 or during the DLT period
(i.e. C1D2 [Day 2] through to C2D2 [Day 30]) of the study

3. Have not recovered from AEs (= CTCAE Grade 2 other than alopecia) due to agent(s)
administered more than 4 weeks earlier

4. Radiotherapy within 4 weeks prior to study drug administration

5. Major surgery or significant trauma within 28 days (4 weeks) of Screening

6. Anticipated requirement for surgery or initiation of anti-cancer therapy, other than
described in this study protocol, during the study period

7. Known hypersensitivity to any of the combination partners of ATX-101

8. Any malignancy over the last 5 years, other than ovarian/fallopian tube/primary
peritoneal cancer, with exception of basal cell carcinoma or squamous cell carcinoma
of the skin or carcinoma in situ of the cervix that is considered cured by excision

9. Cardiac failure NYHA III/IV.

10. LVEF < 50% (ECHO or MUGA must not be older than 12 weeks)

11. QTcF > 470 msec

12. Any organ dysfunction or current acute or chronic disease, other than the study
indication, that would significantly increase the expected risk in participants
participating in the study, in the judgment of the Investigator

13. Pregnant or breast-feeding women

14. Unwilling or unable to follow protocol requirements

15. A past positive status of HIV and/or positive for HIV at Screening

16. Active Hepatitis B or C. In participants with a history of Hepatitis B or Hepatitis C
infection, HBsAg and HCV RNA tests have to be negative.

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
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2023
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Mater Misericordiae Limited - South Brisbane
Recruitment hospital [3] 0 0
Peninsula and Southeast Oncology - Frankston
Recruitment hospital [4] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 0 0
St John of God Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
6008 - Subiaco

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
THERAPIM PTY LTD
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b/2a multicenter study, which consists of two parts:

Part 1: the Phase 1b part of the study will investigate the safety of the combination of
ATX-101 with carboplatin/pegylated liposomal doxorubicin (ACD). ATX-101 will be administered
intravenously in three escalation cohorts: 20, 30, and 45 mg/m² according to a 3+3 design. In
the case where 20 mg/m² is not tolerated, the dose can be de-escalated to 15 mg/m².

Part 2: the Phase 2a part of the study will investigate the efficacy and safety of ACD.

ATX-101 will be administered at the dose defined in Part 1 of the study.

Treatment will continue up to six cycles or until disease progression or unacceptable
toxicity, participant withdrawal of consent, non-compliance, lost to follow-up, or withdrawal
at the Investigators discretion, whichever occurs first.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04814875
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tarek Meniawy, A/Prof
Address 0 0
Medical Oncologist, Sir Charles Gairdner Hospital Ground Floor, B Block, Hospital Avenue, Nedlands, WA 6009, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04814875