Trial Title:
(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer
NCT ID:
NCT05607004
Condition:
Breast Neoplasms
Invasive Breast Cancer
Estrogen-receptor-positive Breast Cancer
HER2-negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Exemestane
Goserelin
Conditions: Keywords:
breast cancer
ER+/HER2-
endocrine therapy
neoadjuvant
(Z)-endoxifen
exemestane
goserelin
Ki-67
estrogen receptor negative
human epidermal growth factor receptor 2 negative
Stage II
tamoxifen
PKCB1
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This multicenter open-label study consists of two cohorts: PK and Treatment
The PK Cohort is a dose finding study to identify the dose to use in the Treatment
Cohort.
The Treatment Cohort is a randomized 1:1 two-arm study with potential to switch to a
single modified regimen based on Ki-67% at Week 4.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
(Z)-endoxifen
Description:
(Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg
capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).
Arm group label:
PK Cohort
Arm group label:
PK Cohort 80 mg
Arm group label:
PK Cohort 80 mg + OFS
Arm group label:
Treatment Cohort Arm 1 Initial Regimen
Arm group label:
Treatment Cohort Arm 1 Modified Regimen
Arm group label:
Treatment Cohort Arm 2 Modified Regimen
Other name:
endoxifen
Intervention type:
Drug
Intervention name:
exemestane
Description:
exemestane tablets 25 mg
Arm group label:
Treatment Cohort Arm 2 Initial Regimen
Other name:
Aromasin
Intervention type:
Drug
Intervention name:
goserelin
Description:
goserelin 3.6 mg subcutaneous implant
Arm group label:
PK Cohort 80 mg + OFS
Arm group label:
Treatment Cohort Arm 1 Modified Regimen
Arm group label:
Treatment Cohort Arm 2 Initial Regimen
Arm group label:
Treatment Cohort Arm 2 Modified Regimen
Other name:
Zoladex
Summary:
This open-label research study is studying (Z)-endoxifen as a possible treatment for
pre-menopausal (still having periods) women with ER+/HER2- breast cancer. (Z)-endoxifen
is a selective estrogen receptor modulator or "SERM." SERMs work to treat cancer by
blocking the body's natural estrogen from binding to cancer cells. This study includes a
pharmacokinetic part (PK, how the drug works in your body) and a treatment part. The
primary purpose of the study is to see how (Z)-endoxifen works on tumor cell growth by
monitoring a cancer marker called Ki-67. Ki-67 will be measured by biopsy of the breast
after about 4 weeks of treatment. If your cancer is responding to treatment based on the
Ki-67 results, you may continue treatment up to 24 weeks or until surgery.
The PK part of the study will be enrolled first, enrolling about 18 study participants
who will all receive oral once daily (Z)-endoxifen treatment. 12 of these participants
will be randomly assigned to treatment with an equal (50/50) chance to be assigned to
(Z)-endoxifen or (Z)-endoxifen + goserelin (a medication given to block the ovaries from
making estrogen and is also called ovarian suppression). This part of the study will help
select the dose of (Z)-endoxifen to use in the treatment part by measuring the levels of
(Z)-endoxifen in the blood stream and determine how long it takes for the body to remove
it.
About 160 study participants will be enrolled in the treatment part. The treatment part
will help to determine how oral once daily (Z)-endoxifen, when taken by itself, compares
to oral once daily exemestane (a medication that decreases the amount of estrogen in the
body, also known as an aromatase inhibitor) and monthly injections of goserelin.
Exemestane and goserelin taken together is a standard treatment regimen for premenopausal
patients with ER+/HER2- breast cancer. Study participants are randomly assigned to
treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen or standard
treatment.
Study participation is up to 24 weeks of treatment followed by surgery.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Premenopausal women 18 years or older
- Not lactating, pregnant, or planning to become pregnant in the next year
- Agree to use at least one non-hormonal highly effective method of contraception for
the entire duration of study participation.
- ER+/HER2-: [ER] ≥ 67% or Allred Score 6-8) / HER2- (histologically confirmed) using
American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP)
guidelines
- Clinical T2 or T3 and N0 or N1 invasive breast cancer (per American Joint Committee
on Cancer [AJCC] 8th edition clinical staging)
- Nottingham Grade 1 or 2
- ECOG Performance Status (ECOG PS) of 0 to 2
Exclusion Criteria:
- Inflammatory breast cancer; bilateral disease (DCIS/LCIS in contralateral breast OK)
- Prior diagnosis or treatment for breast cancer, including carcinoma in situ, or
history of any other active malignancy within the past 2 years prior to study entry
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring systemic treatment with strong
inhibitors/inducers of CYP450 enzymes (including bacterial infection, fungal
infection, or detectable viral infection).
- Symptomatic congestive heart failure, unstable angina pectoris, uncontrolled
symptomatic cardiac arrhythmias
- Uncontrolled hypertension (defined as blood pressure > 160/90 mm Hg)
- Uncontrolled diabetes (Hemoglobin A1c [HbA1c] >7%)
- Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
QTc interval > 470 milliseconds [msec]) using Fridericia's QT correction formula
seen ≤ 28 days of registration
- Known cataracts or retinopathy
- History of deep vein thrombosis (DVT)/pulmonary embolism (PE)
- Known activated protein C (APC) resistance, an inherited coagulation disorder
- Creatine clearance < 60 ml/min
- Total bilirubin ≥ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine amino transferase (ALT) ≥ 2.5 x ULN
- Platelet count (PLT) ≤ 75,000/mm3
- Hemoglobin (Hb) ≤ 10 g/dL
- Hormonal therapies including birth control and hormone replacement therapy during
the study or within 1 week of registration; androgen therapy
- Allergy to endoxifen, goserelin, or exemestane or any of their components
- Participation in another investigational clinical trial ≤ 6 months of registration
- Known metastatic disease
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic Arizona
Address:
City:
Phoenix
Zip:
85054
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Lida Mina, MD
Email:
Principal Investigator
Facility:
Name:
University of Arizona
Address:
City:
Tucson
Zip:
85719
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Sima Ehsani, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic Florida
Address:
City:
Jacksonville
Zip:
32224
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Pooja Advani, MD
Email:
Principal Investigator
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Seema Khan, MD
Email:
Principal Investigator
Facility:
Name:
St. Elizabeth Healthcare
Address:
City:
Edgewood
Zip:
41017
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Daniel Flora, MD
Email:
Principal Investigator
Facility:
Name:
Henry Ford Cancer Institute
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Vrushali Dabak, MD
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Matthew Goetz, MD
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Nusayba Bagegni, MD
Email:
Principal Investigator
Facility:
Name:
Avera Cancer Institute
Address:
City:
Sioux Falls
Zip:
57105
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Jason Jones, MD
Email:
Principal Investigator
Facility:
Name:
Tranquility Research
Address:
City:
Webster
Zip:
77598
Country:
United States
Status:
Withdrawn
Start date:
February 14, 2023
Completion date:
September 2026
Lead sponsor:
Agency:
Atossa Therapeutics, Inc.
Agency class:
Industry
Collaborator:
Agency:
InClin
Agency class:
Other
Source:
Atossa Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05607004
