A Study of ZN-c3 in Patients With Platinum-Resistant Ovarian Cancer
Solid Tumor, Epithelial Ovarian Cancer, Fallopian Tube Cancer
About this trial
This is an interventional treatment trial for Solid Tumor focused on measuring Solid Tumor
Eligibility Criteria
Inclusion Criteria:
- Provision of written informed consent prior to initiation of any study-related procedures that are not considered standard of care.
- Females ≥ 18 years of age 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 therapeutic regimens/lines of therapy in the metastatic setting.
- 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:
- 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.
- Platelet count ≥ 100 × 10^9/L; excluding measurements obtained within 3 days after transfusion of platelets.
- 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.
- Total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the case of Gilbert's disease.
- 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:
- Major surgery within 28 days.
- Radiation therapy within 21 days.
- Autologous or allogeneic stem cell transplant within 3 months.
A serious illness or medical condition(s) including, but not limited to, the following:
- Brain metastases that require immediate treatment or are clinically or radiologically unstable.
- Leptomeningeal disease that requires or is anticipated to require immediate treatment.
- Myocardial impairment of any cause.
- Significant gastrointestinal abnormalities.
- 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 > 480 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.
Sites / Locations
- Site 0264Recruiting
- Site 0104Recruiting
- Site 0111Recruiting
- Site 0173Recruiting
- Site 0259Recruiting
- Site 0191Recruiting
- Site 0196Recruiting
- Site 0103Recruiting
- Site 2707Recruiting
- Site 2708Recruiting
- Site 2706Recruiting
- Site 2705Recruiting
- Site 1001Recruiting
- Site 1002
- Site 1003Recruiting
- Site 1202
- Site 1201
- Site 1401Recruiting
- Site 2901Recruiting
- Site 2903Recruiting
- Site 2904Recruiting
- Site 1902Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Combination with carboplatin
Combination with PLD
Combination with paclitaxel
Combination with gemcitabine
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)
Participants will take: (1) ZN-c3 orally and continuously once daily (QD) in 28-day treatment cycles (± 3 days), and (2) PLD 40 mg/m^2 intravenously over 60 minutes every 4 weeks, on Day 1 of each 28-day cycle
Participants will take: (1) ZN-c3 orally and continuously once daily (QD) in 28-day treatment cycles, and (2) paclitaxel 80 mg/m^2 administered intravenously over 60 minutes (± 10 minutes) on Days 1, 8, and 15 of each 28-day cycle
Participants will take: (1) ZN-c3 orally and continuously once daily (QD) in 21-day treatment cycles, and (2) gemcitabine 1000 mg/m^2 intravenously over 30 minutes or longer every 3 weeks, on Day 1 of each 21-day cycle. If the dose of 1000 mg/m2 is deemed to have unacceptable toxicity in combination with ZN-c3, lower doses may be assessed.