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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04516447




Registration number
NCT04516447
Ethics application status
Date submitted
11/08/2020
Date registered
18/08/2020
Date last updated
7/05/2021

Titles & IDs
Public title
A Study of ZN-c3 in Patients With Platinum-Resistant Ovarian Cancer
Scientific title
A Phase 1b Study of ZN-c3 in Combination With Chemotherapy in Patients With Platinum-Resistant Ovarian, Peritoneal or Fallopian Tube Cancer
Secondary ID [1] 0 0
ZN-c3-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Epithelial Ovarian Cancer 0 0
Fallopian Tube Cancer 0 0
Peritoneal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZN-c3
Treatment: Drugs - Carboplatin
Treatment: Drugs - Pegylated liposomal doxorubicin

Experimental: Combination with carboplatin - Participants will take: (1) ZN-c3 orally and continuously once daily (QD) in 21-day treatment cycles (± 3 days), and (2) carboplatin 5 mg/mL*min intravenously over 15 minutes or longer every 3 weeks, on Day 1 of each 21-day cycle (± 3 days)

Experimental: Combination with PLD - Participants will take: (1) ZN-c3 orally and continuously once daily (QD) in 28-day treatment cycles (± 3 days), and (2) PLD 50 mg/m^2 intravenously over 60 minutes every 4 weeks, on Day 1 of each 28-day cycle


Treatment: Drugs: ZN-c3
Investigational drug

Treatment: Drugs: Carboplatin
Carboplatin is an approved drug

Treatment: Drugs: Pegylated liposomal doxorubicin
Pegylated liposomal doxorubicin (PLD) is an approved drug

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To investigate the safety and tolerability of ZN-c3 in combination with PLD and with carboplatin, respectively - Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
Timepoint [1] 0 0
Through completion, approximately 24 months
Primary outcome [2] 0 0
To identify the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of ZN-c3 in combination with PLD and with carboplatin, respectively - Incidence and severity of dose-limiting toxicities (DLTs) in DLT-evaluable subjects during Cycle 1
Timepoint [2] 0 0
Through Cycle 1 (cycle is 28 days for PLD, and 21 days for carboplatin)
Secondary outcome [1] 0 0
To obtain estimates of clinical activity by determining the objective response rate (ORR) of ZN-c3 in combination with PLD and with carboplatin, respectively - Objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1
Timepoint [1] 0 0
Through completion, approximately 24 months
Secondary outcome [2] 0 0
To obtain estimates of clinical activity by determining the duration of response (DOR) of ZN-c3 in combination with PLD and with carboplatin, respectively - Duration of response (DOR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1
Timepoint [2] 0 0
Through completion, approximately 24 months
Secondary outcome [3] 0 0
To obtain estimates of clinical activity by determining the progression-free survival (PFS) of ZN-c3 in combination with PLD and with carboplatin, respectively - Progression-free survival (PFS) as defined by RECIST version 1.1 and clinical criteria
Timepoint [3] 0 0
Through completion, approximately 24 months
Secondary outcome [4] 0 0
To obtain estimates of clinical activity by determining the time to CA125 progression of ZN-c3 in combination with PLD and with carboplatin, respectively - Time to CA125 progression according to the Gynecologic Cancer Intergroup (GCIG) criteria
Timepoint [4] 0 0
Through completion, approximately 24 months
Secondary outcome [5] 0 0
To investigate the plasma pharmacokinetics (PK) of ZN-c3 in combination with PLD and with carboplatin, respectively - Plasma PK parameters of ZN-c3 (and its potential metabolites as applicable)
Timepoint [5] 0 0
Through completion, approximately 24 months

Eligibility
Key inclusion criteria
- Provision of written informed consent prior to initiation of any study-related
procedures that are not considered standard of care.

- Age = 18 years or the minimum legal adult age (whichever is greater) at the time of
informed consent.

- ECOG performance status = 2.

- Histologically or cytologically confirmed high-grade serous epithelial ovarian
carcinoma, fallopian tube, or peritoneal carcinoma.

- Subjects must have received 1 or 2 prior chemotherapy regimens.

- The disease must be platinum-resistant, i.e., the Platinum-Free Interval (PFI) must
have been < 6 months. Platinum refractory disease, i.e., PD during first-line
platinum-based therapy is allowed.

- Measurable disease per RECIST version 1.1.

- Adequate hematologic and organ function as defined by the following criteria:

1. ANC = 1.5 × 10^9/L; excluding measurements obtained within 7 days after daily
administration of filgrastim/sargramostim or within 3 weeks after administration
of pegfilgrastim.

2. Platelet count = 100 × 10^9/L; excluding measurements obtained within 3 days
after transfusion of platelets.

3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 × upper
limit of normal (ULN). If liver function abnormalities are due to underlying
liver metastases, AST and ALT = 5 x ULN.

4. Total serum bilirubin = 1.5 × ULN or = 3 × ULN in the case of Gilbert's disease.

5. Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 60 mL/min.

- Female subjects of childbearing potential must have a negative serum beta human
chorionic gonadotropin (ß-hCG) test and agree to use an effective method of
contraception per institutional standard.

- Left ventricular ejection fraction (LVEF) = 50% or within normal limits of the
institution (only for subjects treated with PLD).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Histology of abdominal adenocarcinoma of unknown origin or diagnosis of a borderline
ovarian tumor.

- Any of the following treatment interventions within the specified time frame prior to
Cycle 1 Day 1:

1. Major surgery within 28 days.

2. Radiation therapy within 21 days.

3. Autologous or allogeneic stem cell transplant within 3 months.

- A serious illness or medical condition(s) including, but not limited to, the
following:

1. Brain metastases that require immediate treatment or are clinically or
radiologically unstable.

2. Leptomeningeal disease that requires or is anticipated to require immediate
treatment.

3. Myocardial impairment of any cause.

4. Significant gastrointestinal abnormalities.

5. Active or uncontrolled infection.

- Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade 2
neuropathy, alopecia or skin pigmentation).

- Pregnant or lactating females (including the cessation of lactation) or females of
childbearing potential who have a positive serum pregnancy test within 14 days prior
to Cycle 1 Day 1.

- Subjects with active (uncontrolled, metastatic) second malignancies or requiring
therapy.

- 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula (QTcF) of
> 450 msec, except for subjects with atrioventricular pacemakers or other conditions
(e.g., right bundle branch block) that render the QT measurement invalid.

- History or current evidence of congenital long QT syndrome.

- Taking medications that lead to significant QT prolongation.

- Administration of strong and moderate CYP3A4 inhibitors and inducers as well as strong
and moderate P-glycoprotein (P-gp) inhibitors.

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
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Site 2707 - South Brisbane
Recruitment hospital [2] 0 0
Site 2708 - Sunshine Coast
Recruitment hospital [3] 0 0
Site 2706 - Melbourne
Recruitment hospital [4] 0 0
Site 2705 - Nedlands
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
4556 - Sunshine Coast
Recruitment postcode(s) [3] 0 0
3144 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
Bosnia and Herzegovina
State/province [2] 0 0
Banja Luka
Country [3] 0 0
Bosnia and Herzegovina
State/province [3] 0 0
Sarajevo
Country [4] 0 0
Bulgaria
State/province [4] 0 0
Panagyurishte
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Sofia
Country [6] 0 0
Georgia
State/province [6] 0 0
Tbilisi
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Seoul
Country [8] 0 0
Serbia
State/province [8] 0 0
Belgrade

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
K-Group Beta
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability,
preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of ZN-c3 in
combination with other drugs.
Trial website
https://clinicaltrials.gov/show/NCT04516447
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Philippe Pultar, MD
Address 0 0
K-Group Beta
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Project Director
Address 0 0
Country 0 0
Phone 0 0
8582634333
Fax 0 0
Email 0 0
info@zenopharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04516447