Description:
This is a Phase 1/2, open-label, multicenter, 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. ZN-c5 will be evaluated both as monotherapy
and in combination with palbociclib (IBRANCE®).
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
Interventions
Drug | Synonyms | Arms |
---|
ZN-c5 | | ZN-c5 monotherapy |
Palbociclib | IBRANCE® | 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
Name | Type | Description | Interventions |
---|
ZN-c5 monotherapy | Experimental | Sequential 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 + palbociclib combination therapy | Experimental | After 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. | |
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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