Clinical trial NCT04097756: A Phase I Study of LX-039 Tablets
Official title: A Phase I Study of LX-039 Tablets in Postmenopausal Patients With ER+, HER2- Advanced Breast Cancer After Failure of Endocrine Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Breast Cancer
Lead sponsor: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-09-20
Enrollment: 44
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I dose escalation and expansion study in patients with ER+, HER2- advanced breast cancer to explore the tolerance, PK/PD(pharmacokinetics/pharmacodynamics) profiles and preliminary anti-tumor activity of different doses of LX-039 tablets. The trial consists of two parts, dose escalation and dose expansion. Part 1 is the dose escalation phase with initial 6 dose groups, and "3 + 3" design is used to explore MTD of the drug; Part 2 is the dose expansion phase with 2 \~ 3 doses selected for expansion according to the escalation results of Part 1, and more subjects are enrolled to further observe the tolerance and preliminary anti-tumor activity of the drug. After the completion of dose expansion, the recommended phase II dose (RP2D) will be determined after discussion based on the obtained tolerance and PK/PD data.


Eligibility criteria: Inclusion Criteria:

1. Be able to read and sign the informed consent form.
2. Adult females (aged ≥18 and ≤75 years).
3. Be diagnosed with breast cancer confirmed by pathological examination.
4. Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
5. Be postmenopausal.
6. Subjects who have previously received endocrine therapy and obtained benefit.
7. ECOG(Eastern Cooperative Oncology Group) score ≤ 1.
8. Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
9. Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
10. Enough hematology and organ function.
11. Expected survival\>3 months.

Exclusion Criteria:

1. Subjects with HER2-overexpressing breast cancer.
2. Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
3. Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
4. Subjects who received second-line or above chemotherapy.
5. Subjects with known allergy to this product or any of its components.
6. Subjects who previously used other estrogen receptor down regulators than fulvestrant.
7. Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
8. Subjects who received cell therapy or tumor vaccine therapy;
9. Subjects with severe immunosuppression .
10. Severe or uncontrolled disease.
11. Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
12. Subjects with other malignancy within 5 years prior to study entry.
13. Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
14. Subjects with history of definite neurological or psychiatric disorders in the past.
15. Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
16. Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.

Primary outcomes:
measure: To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer
timeFrame: DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)
Secondary outcomes:
measure: The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer
timeFrame: through study completion,an average of 1 year
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
timeFrame: through study completion，an average of 1 year.
measure: Comparison of changes in maximum uptake ability of FES(progression free survival) in breast cancer lesions before and after treatment with LX-039 by PET(positron emission tomography) scan (performed in some subjects)
timeFrame: Up to the third day of Cycle 2(each cycle is 28 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after a single dose of LX-039
timeFrame: Up to the third day of Cycle 0(Cycle 0 is 7 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
measure: PK profiles after continuous administration of LX-039
timeFrame: Up to the Second day of Cycle 2(each cycle is 28 days)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References:
citation: Lu J, Chan CC, Sun D, Hu G, He H, Li J, Dong J, Liu K, Shen L, Hu L, Gu Q, Chen S, Wang T, Gong T, Tang W, Li X, Zhu X, Zeng X, Zhu Y, Xia Y, Huang Y, Zhu Y, Liu Z, Ding CZ. Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD). Bioorg Med Chem Lett. 2022 Jun 15;66:128734. doi: 10.1016/j.bmcl.2022.128734. Epub 2022 Apr 15.