Clinical Trials /

A Study of ZN-c3 in Patients With Platinum-Resistant Ovarian Cancer

NCT04516447

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: ZN-c3-002
  • NCT ID: NCT04516447

Conditions

  • Solid Tumor
  • Epithelial Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer

Interventions

DrugSynonymsArms
ZN-c3Study drugCombination with PLD
CarboplatinCombination with carboplatin
Pegylated liposomal doxorubicinCombination with PLD

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Combination with carboplatinExperimentalParticipants 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)
  • ZN-c3
  • Carboplatin
Combination with PLDExperimentalParticipants 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
  • ZN-c3
  • Pegylated liposomal doxorubicin

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To investigate the safety and tolerability of ZN-c3 in combination with PLD and with carboplatin, respectively
Time Frame:Through completion, approximately 24 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:To obtain estimates of clinical activity by determining the objective response rate (ORR) of ZN-c3 in combination with PLD and with carboplatin, respectively
Time Frame:Through completion, approximately 24 months
Safety Issue:
Description:Objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1
Measure:To obtain estimates of clinical activity by determining the duration of response (DOR) of ZN-c3 in combination with PLD and with carboplatin, respectively
Time Frame:Through completion, approximately 24 months
Safety Issue:
Description:Duration of response (DOR) as defined by Response Evaluation Criteria in Solid Tumors RECIST version 1.1
Measure:To obtain estimates of clinical activity by determining the progression-free survival (PFS) of ZN-c3 in combination with PLD and with carboplatin, respectively
Time Frame:Through completion, approximately 24 months
Safety Issue:
Description:Progression-free survival (PFS) as defined by RECIST version 1.1 and clinical criteria
Measure: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 Frame:Through completion, approximately 24 months
Safety Issue:
Description:Time to CA125 progression according to the Gynecologic Cancer Intergroup (GCIG) criteria
Measure:To investigate the plasma pharmacokinetics (PK) of ZN-c3 in combination with PLD and with carboplatin, respectively
Time Frame:Through completion, approximately 24 months
Safety Issue:
Description:Plasma PK parameters of ZN-c3 (and its potential metabolites as applicable)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:K-Group Beta

Trial Keywords

  • Solid Tumor

Last Updated

March 23, 2021