Trial Title:
Study of TFX06 in Women With Advanced Breast Cancer.
NCT ID:
NCT05927779
Condition:
ER+, HER2- Advanced Breast Cancer
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TFX06 tablet
Description:
TFX06 tablet taken orally
Arm group label:
Dose escalation
Summary:
A Phase 1/2 Dose Escalation and Expansion Study of TFX06 tablet Alone in Women with ER
Positive, HER2 Negative Advanced Breast Cancer
Detailed description:
This is a phase Ⅰ/Ⅱ, open-label study of TFX06 tablet single agent to assess the safety
and tolerability, identify an Maximum Tolerated Dose （MTD）, and/or RP2D, evaluate the
pharmacokinetic（PK ）properties and evaluate preliminary anti-tumor activities in women
with advanced or metastatic ER-positive, HER2-negative breast cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. voluntary participation in clinical trials and signature of informed consent, and be
willing to comply with the requirements of the protocol Seek.
2. Age>= 18 years.
3. Postmenopausal status defined as meeting at least one of the following criteria:
1. Have undergone a bilateral oophorectomy any time in life.
2. Age ≥ 60 years.
3. Age<60 years but have natural menopause ≥ 12 months with estradiol (E2)and
follicle stimulating hormone (FSH) levels in the postmenopausal range without
chemical ablation(chemotherapy,toremifene, tamoxifen, or ovarian castration
drugs).
4. Premenopausal or perimenopausal concurrently given a luteinizing
hormone-releasing hormone (LHRH) agonist starting before the start of trial
therapy and is planned to continue LHRH agonist during the study.
4. Subjects are willing to provide blood for Estrogen Receptor 1 (ESR1)mutation status
analysis.
5. The ECOG score is 0-1 and has not deteriorated in the past 2 weeks.
6. Expected survival ≥ 3 months.
7. Histologically or cytologically confirmed breast cancer.
8. Latest primary or metastatic tumor biopsy confirmed positive for Estrogen Receptors
(ER+) and negative for HER2 (HER2-) receptor (subject to local laboratory
pathological test results).
9. Prior therapy is restricted as follows:
1. No more than 2 lines of chemotherapy for advanced/metastatic breast cance or
cannot tolerate standard chemotherapy (if disease progression/recurrence occurs
more than 12 months after the end of previous neoadjuvant/adjuvant
chemotherapy, it will not be included in line 1 chemotherapy; otherwise, it
will be included in line 1 chemotherapy).
2. Prior to receiving standard endocrine therapy for at least 6 months or being
unable to tolerate standard endocrine therapy (including selective estrogen
receptor modulator (SERM) or aromatase inhibitors) for adjuvant therapy or
advanced/metastatic diseases, and the disease progresses during endocrine
therapy, Prior treatment with selective estrogen receptor degrade (SERD)is not
allowed.
Note:For Part A, There is no limit on the number of lines of prior endocrine
therapies, and multiple lines of endocrine therapy are allowed; For Part B, Prior
endocrine therapy must be combination therapy or sequential therapy of CDK4/6 and
AI.
10. At least one lesion (measurable and/or non-measurable, as per RECIST 1.1) Patients
who planning to undergo 18F-FES PET-CT examination must have at least one measurable
lesion located outside the bladder, small intestine and liver that meets RECIST v1.1
with a maximum diameter of ≥ 15mm.
11. Adequate bone marrow function (within 2 weeks (14 days) prior to study treatment) as
defined below and not requiring blood transfusion or growth factor (GCSF, EPO, etc.)
support
1. Hemoglobin (Hb) ≥ 90 g/L.
2. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L.
3. Platelet count (PLT) ≥ 75 × 10^9/L.
12. Adequate liver function is defined as follows:
1. Total bilirubin (TBIL) ≤ 1.5 × ULN； For patients with Gilbert syndrome or
familial benign unconjugated hyperbilirubinemia TBIL ≤ 2.5 × ULN.
2. AST and ALT≤ 3 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver
metastases are present
13. Good renal function, defined as creatinine ≤ 1.5 × ULN, or creatinine clearance rate
(Ccr)>60 mL/min. The modified Cockcroft Gault formula was used to estimate
creatinine clearance. Calculate Ccr: Ccr=[(140 age) × Body weight (Kg) × (Female
0.85)]/(72 × Serum creatinine), without obvious electrolyte disturbances that are
not easily corrected.
14. Coagulation function: International standardized ratio (INR) or prothrombin time
(PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (unless the
subject is receiving anticoagulation therapy and the level of the patient receiving
anticoagulation therapy should be within the treatment range). If the patient is
receiving anticoagulation treatment, the investigator should closely monitor these
laboratory test values.
Exclusion Criteria:
1. History of any clinically significant disease or disorder which, in the opinion of
the investigator, may either put the subject at risk because of participation in the
study, or influence the results or the subject's ability to participate in the
study.
2. Any unresolved toxicities from prior therapy > CTCAE Grade 1 at the time of starting
Investigational Medicinal Product(IMP), with the exception of alopecia..
3. Received systemic cytotoxic chemotherapy, immunotherapy, targeted therapy anti tumor
biological therapy or major surgery (Special cases: treatment with nitrourea or
mitomycin C requires a 6 weeks washout period; oral fluorouracil drugs require a
2-week washout period; small molecule targeted treatment requires a 2-week washout
period; treatment with traditional Chinese patent medicines and simple preparations
approved by National Medical Products Administration(NMPA) requires a 2-week washout
period, including: compound cantharides capsule, Kangai injection, Kanglaite
capsule/injection, Aidi injection, Brucea javanica oil injection/capsule, Xiao ai
ping tablet/injection, cinobufagin capsule, etc.) within 4 weeks prior to first dose
of study drug.or obvious traumatic injury, wounds or fractures that have not been
healed for a long time, except for pathological fractures.
4. Prior use of experimental SERD or experimental ER antagonist treatment. However, it
is allowed to receive fluvastatin treatment.
Note: Patients planning to undergo 18F-FES PET-CT examination: If the end line
treatment is a drug that acts on estrogen receptors such as fluvastatin, the 18F-FES
PET-CT examination should have a 5 half life from the last medication, a time period
of>6 months from the last use of fluvastatin, and a time period of ≥ 5 weeks from
the last use of tamoxifen;
5. Systemic radiation therapy within 28 days or local radiation therapy within 7 days
prior to first dose of study drug.
6. Patients who are receiving treatment with medications that are known to be strong
inhibitors or inducers of CYP3A within 14 day or 5 half- life (whichever is shorter)
prior to first dose of study treatment.
7. Participated in other clinical trials within 30 days before the first medication or
received clinical trial medication within 5 half-lives of the first medication
(whichever is longer).
8. The patient is receiving other approved or experimental anticancer treatments.
9. Major surgery within 14 days before the first dose of the study drug or not
recovered from serious side effects.
10. Known other malignant tumors within 3 years before enrollment (except fully treated
basal or squamous cell carcinoma, non melanoma skin cancer, or radical cervical
cancer.)
11. Known active central nervous system(CNS) metastasis and/or meningitis carcinomatosa:
subjects with treated brain metastases may be eligible if their condition is stable
and they do not have the following conditions:
1. Progressive or new onset of neurological impairment, seizures, evidence of
Raised intracranial pressure, vomiting, papilledema, or headache;
2. CNS tumor recurrence/progression confirmed by MRI at least 4 weeks before the
first administration of this study
3. Evidence of new or enlarged brain metastases and no corticosteroids were used
at least 3 days prior to the administration of the study drug.
Two brain MRI scans used to confirm the stability of CNS disease must be submitted
to the sponsor, preferably when the subject is being screened.
12. The patient is unable to swallow the preparation, or gastrointestinal disease that
may affect the absorption of the study drug (e.g., previous partial or complete
gastrectomy, previous Rouxen-Y or Whipple surgery, untreated gastric or duodenal
ulcer, uncontrolled/refractory nausea, vomiting, diarrhea, malabsorption syndrome,
or major bowel resection).
13. The patient is currently receiving proton pump inhibitors(PPI)treatment. PPI
treatment must be stopped 1 week or earlier before the first administration of
TFX06.
14. According to the judgment of the sponsor/investigator, the patient currently suffers
from any other serious and/or uncontrollable medical disease (e.g., severe liver
damage, etc.) that is not suitable for participation in the clinical study.
15. The patient currently has a record of grade 1 (or higher) pneumonia or interstitial
lung disease (ILD) (no associated pulmonary complications confirmed by baseline
chest CT scans ).
16. Ophthalmological examination during the screening period confirmed clinically
significant ocular lesions and were not suitable to participate in this study
according to the judgment of the investigator.
17. The patient has clinically significant, uncontrolled heart disease and/or recent
cardiac events, including any of the following:
1. History of angina, coronary artery bypass grafting (CABG), symptomatic
pericarditis, or myocardial infarction within 12 months prior to the start of
study treatment.
2. Recorded history of congestive heart failure (New York Heart Association
Cardiac Function Classification III-IV).
3. Recorded cardiomyopathy.
4. Determination of a patient's left ventricular ejection fraction (LVEF)<50%
using multi gated acquisition (MUGA) scans or echocardiography (ECHO).
5. Any history of arrhythmia (such as ventricular tachycardia), complete left
bundle branch block, high degree atrioventricular block (such as double bundle
branch block, Mobitz type II, and third degree atrioventricular block),
supraventricular, nodal arrhythmia, or conduction abnormalities within the past
12 months.
6. Uncontrolled hypertension is defined as systolic blood pressure (SBP) ≥ 160
mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg, with or without use of
antihypertensive drugs. Allow initiation or adjustment of antihypertensive drug
therapy before screening.
7. A family medical history of long QT syndrome, idiopathic sudden death, or
congenital long QT syndrome, or any of the following:
- Risk factors for torsade de pointe ventricular tachycardia (TdP) include
uncontrolled hypokalemia or hypomagnesemia, a history of heart failure, or
a history of clinically significant/symptomatic bradycardia.
- There is a known risk of prolonging the QT interval and/or concomitant
drugs that are known to cause torsade de pointe ventricular tachycardia
and cannot be discontinued or replaced with safe alternative drugs.
8. Bradycardia (resting heart rate<50), measured by ECG or pulse.
9. During screening, the ECG examination was unable to determine the QTcF interval
(i.e., unreadable or unreadable), or corrected for QT (QTcF)>460 ms (female)
(using fridericia correction). All were determined by screening period ECG
(mean of three ECGs).
18. Patient is currently receiving or has received systemic corticosteroid treatment
within 2 weeks prior to the start of study treatment. or has not fully recovered
from the side effects of such treatment. However, it is allowed to use
corticosteroids in the following situations: single administration, local
application (e.g. for rash), inhalation spray (e.g. for obstructive airway disease),
eye drops or local injection (e.g. in joints).
19. Evidence of severe or uncontrolled systemic disease, including active hemorrhagic
constitution.
20. History of bleeding, thrombosis, and cancer thrombus:
1. Have clinically significant bleeding symptoms or clear bleeding tendencies
within 3 months prior to screen;
2. History of gastrointestinal bleeding or a clear tendency to gastrointestinal
bleeding within 3 months prior to screen;
3. History of arterial/venous thrombotic events that occurred within 6 months
prior to screen, such as cerebrovascular accidents (including transient
ischemic attacks), pulmonary embolism, etc;
4. The presence of tumor thrombi was confirmed by imaging examination within 6
months prior to screen.
21. Known active hepatitis B or hepatitis C infection.
22. Known serious, uncontrolled infection or known infection with human immunodeficiency
virus (HIV) (HIV1/2 antibody), diagnosis of acquired immunodeficiency syndrome
(AIDS)，uncontrolled autoimmune diseases, or patients who have previously received a
tissue/organ transplant, stem cell or bone marrow transplant.
23. Uncontrolled active bacterial, viral, fungal, rickettsia, or parasitic infections
unless treated and resolved prior to study treatment.
24. Received a live viral vaccine within 30 days prior to the first administration of
the study drug. Allow the use of seasonal influenza or approved COVID-19 vaccines
that do not contain live viruses.
25. Other conditions that the investigator considers unsuitable for this study
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The 1st Affiliated Hospital of Henan University of Science and Technology
Address:
City:
Luoyang
Zip:
471003
Country:
China
Status:
Recruiting
Contact:
Last name:
zhi ye Zhang
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200120
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
jian zhang, phD
Phone:
021-64175590
Email:
syner2000@163.com
Investigator:
Last name:
jian zhang, phD
Email:
Principal Investigator
Start date:
April 17, 2023
Completion date:
April 30, 2025
Lead sponsor:
Agency:
Shenzhen Yangli Pharmaceutical Technology Co., Ltd
Agency class:
Industry
Source:
Shenzhen Yangli Pharmaceutical Technology Co., Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05927779
