Clinical trial for patients with advanced breast cancer

Phase 1

Conditions: Estrogen-receptor positive, human epidermal growth factor receptor-2 negative advanced breast cancer
MedDRA version: 21.1Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-001364-27-CZ

Lead Sponsor: Zeno Alpha, Inc.,

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 181

Inclusion Criteria

1) Male or female
2) Age = 18 years
3) Menopausal Status [Female subjects]:
Postmenopausal, as defined by at least one of the following
a) Age = 60 years;
b) 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;
c) Documented bilateral oophorectomy;
or
Pre- or peri-menopausal, who must receive a gonadotropin-releasing hormone agonist
beginning at least 4 weeks prior to first dose of study medication.
4) Histologically or cytologically confirmed diagnosis of advanced adenocarcinoma of the breast, not
amenable to any potential curative intervention
5) Estrogen Receptor (ER) positive disease defined as follows documented by a local laboratory:
a) [Monotherapy Escalation and Combination Dose Escalation Cohorts]: > 1% positive stained cells
based on medical record, archival tumor biopsy, or de novo tumor biopsy
b) [Monotherapy Expansion/Monotherapy Phase 2/Combination Phase 2 Cohorts]: > 10% positive
stained cells
6) Human Epidermal Growth Factor Receptor 2 (HER2) negative disease as documented by a local
laboratory
a) [Monotherapy Escalation and Combination Dose Escalation Cohorts]: Documentation by medical
record or archival tumor tissue allowed
b) [Monotherapy Expansion/Monotherapy Phase 2/Combination Phase 2 Cohorts]: Based on
analysis of archival tumor biopsy or de novo biopsy with HER2-negativity defined as: 1)
Immunohistochemistry score 0/1+ or 2) Negative by in situ hybridization (FISH/CISH/SISH)
defined as a HER2/CEP17 ratio < 2, or for single probe assessment a HER2 copy number < 4
7) [Monotherapy Escalation and Combination Dose Escalation Cohorts]: Refractory to or intolerant of
established therapy(ies) known to provide clinical benefit for their malignancy
8) Prior Hormonal Therapy:
a) [Monotherapy Expansion Cohort]: up to 2 prior lines of endocrine therapy for advanced or
metastatic breast cancer
b) [Monotherapy Phase 2]: 1 prior line of endocrine therapy for advanced or metastatic breast
cancer
c) [Combination Phase 2]: up to 1 prior line of endocrine therapy for advanced or metastatic
breast cancer
d) Subjects who will undergo a FES-PET must have discontinued all prior ER blocking therapy (e.g.,
tamoxifen or fulvestrant) for = 60 days before the day of the examination at baseline.
In counting lines of treatment for advanced/metastatic disease, any change in regimen due to PD or
toxicity will be counted as a separate line of treatment.
9) Documented prior response to endocrine therapy for advanced or metastatic disease (SD, PR, or CR)
lasting > 6 months or disease recurrence after at least 24 months of adjuvant endocrine treatment.
(not required for treatment naïve patients)
10) Prior Chemotherapy:
a) [Monotherapy Dose Escalation Cohort]: Up to 2 prior lines of chemotherapy for the treatment
of advanced breast cancer
b) [Monotherapy Phase 2]: No prior chemotherapeutic regimens for the treatment of advanced
breast cancer
c) [Monotherapy Expansion, Combination Dose Escalation and Combination Phase 2 Cohorts]: Up
to 1 prior line of chemotherapy for the treatment of advanced breast cancer
In counting lines of treatment for advanced/metastatic disease, any change in regimen due to PD or
toxicity will be counted as a separate line of treatment.
11) Prior treatment with a CDK4/6 inhibitor is allowed
12) Evaluable or measurable disease per RECIST v1.1

Exclusion Criteria

1) Any of the following within the specified window prior to the first dose of study drug:
a) Tamoxifen, AI, fulvestrant or other anti-cancer endocrine therapy < 14 days
b) Any chemotherapy < 28 days (or 5 half-lives, whichever is shorter)
c) Any investigational drug therapy < 28 days or 5 half-lives (whichever is shorter)
d) Prior radiotherapy < 14 days (except for palliative radiotherapy to peripheral sites without
residual toxicity)
e) Major surgery < 28 days
f) Minor surgery < 7 days (placement of central venous catheter, fine needle aspiration, or
endoscopic biliary stent < 1 day is acceptable)
2) Prior hematopoietic stem cell or bone marrow transplantation
3) Prior radiotherapy to > 25% of bone marrow
4) Brain metastases that require immediate treatment or are clinically or radiologically unstable (i.e.,
have been stable for < 1 month). If receiving steroids, subjects must be receiving a stable to
decreasing corticosteroid dose during at least 1 week before enrollment.
5) Leptomeningeal disease that requires or is anticipated to require immediate treatment.
6) Presence of life-threatening metastatic visceral disease or symptomatic pulmonary lymphangitic
spread
7) Other known active cancer(s) likely to require treatment in the next year that would impact the
assessment of any study endpoints
8) [Female subjects]: Pregnant or breast-feeding
9) Unexplained symptomatic endometrial disorders (including, but not limited to endometrial
hyperplasia, dysfunctional uterine bleeding, or cysts)
10) Uncontrolled symptomatic thyroid dysfunction
11) Impairment of gastrointestinal (GI) absorption for oral medications
12) Nausea, vomiting, or diarrhea > Grade 1
13) Myocardial infarction, symptomatic congestive heart failure (NYHA > Class II), unstable angina, or
serious uncontrolled cardiac arrhythmia within the last 6 months
14) QTc interval > 480 msec (based on the mean value of the triplicate ECGs), family or personal history
of long or short QT syndrome, Brugada syndrome or history of Torsade de Pointes
15) Concurrent use of food or drugs known to be moderate or strong CYP3A or CYP2C9 inducers and
moderate or strong CYP3A4 or CYP2C9 inhibitors. In addition, for moderate or strong CYP3A or
CYP2C9 inducers, there should be a wash-out of 14 days (or 5 half-lives, whichever is shorter) before
the first administration of study drug (see Section 10.4.6).
16) Any clinically significant disorder, condition, or disease that, in the opinion of the Investigator or
Medical Monitor would pose a risk to subject safety or interfere with the study evaluations,
procedures, or completion

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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