Brief Title
A Study of ZN-c3 in Patients With Platinum-Resistant Ovarian Cancer
Official Title
A Phase 1b Study of ZN-c3 in Combination With Chemotherapy in Patients With Platinum-Resistant Ovarian, Peritoneal or Fallopian Tube Cancer
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.
Detailed Description
This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability,
preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of ZN-c3. This
study consists of 2 cohorts in participants with platinum-resistant ovarian, peritoneal, or
fallopian tube cancer. One cohort will test a combination of ZN-c3 and pegylated liposomal
doxorubicin (PLD), and the other cohort will test a combination of ZN-c3 and carboplatin.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
To investigate the safety and tolerability of ZN-c3 in combination with PLD and with carboplatin, respectively
Secondary Outcome
To obtain estimates of clinical activity by determining the objective response rate (ORR) of ZN-c3 in combination with PLD and with carboplatin, respectively
Condition
Solid Tumor
Intervention
ZN-c3
Study Arms / Comparison Groups
Combination with carboplatin
Description: 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)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
September 1, 2020
Completion Date
January 1, 2023
Primary Completion Date
October 1, 2022
Eligibility Criteria
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 (β-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).
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Philippe Pultar, MD, 8582634333, [email protected]
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT04516447
Organization ID
ZN-c3-002
Responsible Party
Sponsor
Study Sponsor
K-Group Beta
Study Sponsor
Philippe Pultar, MD, Study Director, K-Group Beta
Verification Date
August 2020