Clinical Trials /

A Study of ZN-c5 in Subjects With Breast Cancer

NCT03560531

Description:

This is a Phase I, open-label, multicenter, sequential dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer who have progressed following endocrine therapy. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE®).

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ZN-c5 in Subjects With Breast Cancer
  • Official Title: A Phase I Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of ZN-c5 Alone and in Combination With Palbociclib in Subjects With Previously Treated Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: ZN-c5-001
  • NCT ID: NCT03560531

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
ZN-c5ZN-c5 monotherapy
PalbociclibIBRANCE®ZN-c5 + palbociclib combination therapy

Purpose

This is a Phase I, open-label, multicenter, sequential dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer who have progressed following endocrine therapy. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE®).

Trial Arms

NameTypeDescriptionInterventions
ZN-c5 monotherapyExperimentalSequential dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5, followed by expansion cohorts at each dose level.
  • ZN-c5
ZN-c5 + palbociclib combination therapyExperimentalAfter the MTD/RP2D of ZN-c5 as monotherapy has been determined, the combination cohort dose escalation will begin enrollment.The expansion cohorts are planned at each dose level.
  • ZN-c5
  • Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years of age who are postmenopausal, as defined by at least one of the
             following:

               -  Age ≥ 60 years;

               -  Age < 60 years and cessation of regular menses for at least 12 consecutive months
                  with no alternative pathological or physiological cause; and serum estradiol and
                  FSH level within the laboratory's reference range for postmenopausal females;

               -  Documented bilateral oophorectomy;

               -  Medically confirmed ovarian failure.

          -  Histologically or cytologically confirmed diagnosis of advanced (metastatic or
             locoregionally recurrent) adenocarcinoma of the breast, not amenable to any potential
             curative intervention

          -  Estrogen Receptor (ER) positive disease

          -  Human Epidermal Growth Factor Receptor 2 (HER2) negative disease

          -  Radiographic documentation of disease progression on the last (most recent) treatment
             administered prior to enrolling in the study.

          -  Documented prior response to endocrine therapy for metastatic disease (SD, PR, or CR
             by RECIST v1.1 criteria) lasting > 6 months

          -  Measurable disease meeting the criteria specified by RECIST v1.1. Tumor lesions
             previously irradiated or subjected to other locoregional therapy will only be deemed
             measurable if progression at the treated site after completion of therapy is clearly
             documented.

        (Note: subjects with bone-only metastatic cancer may be enrolled in the dose escalation
        portion of the study but must have a lytic or mixed lytic-blastic lesion that can be
        accurately assessed by CT or MRI.)

        Exclusion Criteria:

          -  Subjects who have received only neoadjuvant or adjuvant therapy for breast
             adenocarcinoma

          -  Monotherapy: Prior anticancer or investigational drugs for the treatment of ER+/HER2
             negative advanced breast cancer within the following windows:

               -  Tamoxifen, aromatase inhibitor, or other anti-cancer endocrine therapy < 14 days
                  before first dose of study treatment

               -  Any chemotherapy < 28 days before first dose of study

               -  Any investigational drug therapy < 28 days or 3 half-lives (whichever is longer)
                  prior to first dose of study treatment

          -  Combination Therapy: Any prior treatment with any CDK4/6 inhibitor (combination
             cohorts only)

          -  Any prior treatment with immunotherapy (e.g. ipilimumab, nivolumab, pembrolizumab,
             atezolizumab)

          -  Patients with bone-only disease (Dose Expansion cohorts only) Note: Patients with
             bone-only disease may be enrolled in the Dose Escalation portion of the study, but
             must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by CT
             or MRI

          -  Unexplained symptomatic endometrial disorders (including, but not limited to
             endometrial hyperplasia, dysfunctional uterine bleeding, or cysts)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine a maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) for ZN-c5 as a monotherapy
Time Frame:9 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Safety and tolerability of ZN-c5 as a monotherapy as measured by number of treatment-emergent adverse events
Time Frame:Through study completion (approximately 2 years)
Safety Issue:
Description:Measured by the number of treatment-emergent adverse events
Measure:Safety and tolerability of ZN-c5 in combination with palbociclib as measured by number of treatment-emergent adverse events
Time Frame:through study completion (approximately 2 years)
Safety Issue:
Description:Measured by the number of treatment-emergent adverse events

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Zeno Alpha Inc.

Trial Keywords

  • Estrogen receptor
  • Hormone receptor
  • Selective estrogen receptor degrader
  • Hormone sensitive
  • Phase 1

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