Clinical trial NCT03560531: A Study of ZN-c5 in Subjects With Breast Cancer
Official title: A Phase 1/2 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 Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Estrogen receptor
Hormone receptor
Selective estrogen receptor degrader
Hormone sensitive
Phase 1 Dose Escalation
Phase 2 Combination
Phase 1 Dose Expansion
Phase 2 Monotherapy
Lead sponsor: Zeno Alpha Inc.
Sponsor class: INDUSTRY
First posted: 2018-06-18
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation cohorts are planned in monotherapy and combination as well as monotherapy dose expansion, and monotherapy and combination Phase 2.
Primary purpose: TREATMENT

Brief summary: 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®).


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years of age

  * Women can be 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 follicle-stimulating hormone level within the laboratory's reference range for postmenopausal females;
  * Documented bilateral oophorectomy; or can be peri- or premenopausal, however, they must receive a gonadotrophin-releasing hormone agonist beginning at least 4 weeks prior to the first dose of study medication.
* 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
* Documented prior response to endocrine therapy for metastatic disease (stable disease, partial response, or complete response by RECIST v1.1 criteria) lasting \> 6 months
* Evaluable or measurable disease 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.

Exclusion Criteria:

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

  * Tamoxifen, aromatase inhibitor, fulvestrant, or other anti-cancer endocrine therapy \< 14 days before first dose of study treatment
  * Any chemotherapy \< 28 days before first dose of study, except for Phase 2 monotherapy which requires no prior chemotherapy treatment.
  * Any investigational drug therapy \< 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment
* Unexplained symptomatic endometrial disorders (including, but not limited to endometrial hyperplasia, dysfunctional uterine bleeding, or cysts)

Primary outcomes:
measure: Clinical Benefit Rate (CBR) for ZN-c5 as a Monotherapy
timeFrame: 24 weeks
measure: Best Overall Response (BOR) for ZN-c5 as a Monotherapy
timeFrame: 24 weeks
Secondary outcomes:
measure: Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months
timeFrame: 2 months
measure: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months
timeFrame: 4 months
measure: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months
timeFrame: 6 months
measure: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months
timeFrame: 8 months
measure: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months
timeFrame: 10 months
measure: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months
timeFrame: 12 months
measure: Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months
timeFrame: 2 months
measure: Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months
timeFrame: 4 months
measure: Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months
timeFrame: 6 months
measure: Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months
timeFrame: 8 months
measure: Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months
timeFrame: 10 months
measure: Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months
timeFrame: 12 months
measure: Objective Response Rate (ORR) for ZN-c5 as a Monotherapy
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Site 3
state: Arizona
city: Los Angeles
country: United States
facility: Site 5
state: California
city: Bethesda
country: United States
facility: Site 48
state: Maryland
city: Saint Louis
country: United States
facility: Site 47
state: Missouri
city: New York
country: United States
facility: Site 7
state: New York
city: New York
country: United States
facility: Site 2
state: New York
city: Charleston
country: United States
facility: Site 50
state: South Carolina
city: Nashville
country: United States
facility: Site 4
state: Tennessee
city: Houston
country: United States
facility: Site 1
state: Texas
city: Houston
country: United States
facility: Site 8
state: Texas
city: Seattle
country: United States
facility: Site 6
state: Washington
city: Minsk
country: Belarus
facility: Site 46
city: Vitebsk
country: Belarus
facility: Site 45
city: Banja Luka
country: Bosnia and Herzegovina
facility: Site 10
city: Sarajevo
country: Bosnia and Herzegovina
facility: Site 9
city: Tuzla
country: Bosnia and Herzegovina
facility: Site 11
city: Brno
country: Czechia
facility: Site 29
city: Olomouc
country: Czechia
facility: Site 28
city: Praha 5
country: Czechia
facility: Site 30
city: Budapest
country: Hungary
facility: Site 51
city: Kecskemét
country: Hungary
facility: Site 35
city: Pécs
country: Hungary
facility: Site 37
city: Kaunas
country: Lithuania
facility: Site 17
city: Vilnius
country: Lithuania
facility: Site 16
city: Ekaterinburg
country: Russian Federation
facility: Site 42
city: Nizhniy Novgorod
country: Russian Federation
facility: Site 40
city: Omsk
country: Russian Federation
facility: Site 52
city: Pyatigorsk
country: Russian Federation
facility: Site 41
city: Saint Petersburg
country: Russian Federation
facility: Site 39
city: Belgrade
country: Serbia
facility: Site 18
city: Belgrade
country: Serbia
facility: Site 19
city: Niš
country: Serbia
facility: Site 21
city: Novi Sad
country: Serbia
facility: Site 20
city: Cherkasy
country: Ukraine
facility: Site 25
city: Kharkiv
country: Ukraine
facility: Site 27
city: Kropyvnytskyi
country: Ukraine
facility: Site 24
city: Kryvyi Rih
country: Ukraine
facility: Site 26
city: Kyiv
country: Ukraine
facility: Site 23
Study officials:
affiliation: Zeno Alpha Inc.
name: Zeno Alpha, Inc.
role: STUDY_DIRECTOR
References: