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-HU

Lead Sponsor: Zeno Alpha, Inc.,

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 458

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 or 2 prior lines 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 i

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
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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