A Phase I Study of LX-039 Tablets

Advanced Breast Cancer Clinical Trial

Official title:

A Phase I Study of LX-039 Tablets in Postmenopausal Patients With ER+, HER2- Advanced Breast Cancer After Failure of Endocrine Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04097756
• Other study ID #: OE861801
• Status: Completed
• Phase: Phase 1
• Start date: January 7, 2020
• Est. completion date: February 7, 2023

Study information

• Verified date: October 2020
• Source: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: February 7, 2023
• Est. primary completion date: August 8, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• LX-039 tablets
orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, or study termination

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer	Incidence of dose limiting toxicities (DLTs)	DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)
Secondary	The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer	Number of participants with treatment related. adverse events as assessed by CTCAE v5.0	through study completion,an average of 1 year
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	Objective response rate (ORR)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	proportion of subjects with complete response (CR)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	proportion of subjects with partial response (PR)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	proportion of subjects with stable disease (SD)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	proportion of subjects with progressive disease (PD)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	duration of response (DoR)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	disease control rate (DCR)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	clinical benefit rate (CBR)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	time to progression (TTP)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	progression-free survival (PFS)	through study completion,an average of 1 year.
Secondary	To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.	overall survival (OS)	through study completion,an average of 1 year.
Secondary	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)	Decrease in SUVmax in comparison with that before treatment	Up to the third day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after a single dose of LX-039	Peak Concentration (Cmax)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Peak Time (Tmax)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Elimination Half-life (t1/2)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Eliminate Rate Constant (Kel)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Mean Residence Time (MRT)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Area under plasma Concentration-time curve from 0 time to 24 hours (AUC0-24h)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Area under plasma Concentration-time curve from 0 time to sampling time t of the last measurable concentration (AUC0-last)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Area under plasma Concentration-time curve from administration (0) to infinity (AUC0-inf)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Apparent Total Clearance (CL/F)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after a single dose of LX-039	Apparent Volume of Distribution (Vd/F)	Up to the third day of Cycle 0(Cycle 0 is 7 days)
Secondary	PK profiles after continuous administration of LX-039	Trough Concentration at Steady State (Css, min)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Peak Concentration at Steady State (Css, max)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Average Concentration at Steady State (Css, av)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Peak Time (Tss, max)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Apparent Volume of Distribution at steady state (Vss/F)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Steady-state Clearance Half-life (tss,1/2)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Total Body Clearance (CLss/F)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Coefficient of Fluctuation (DF)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Area under Plasma Concentration-time Curve at Steady State (AUCss)	Up to the Second day of Cycle 2(each cycle is 28 days)
Secondary	PK profiles after continuous administration of LX-039	Accumulation Coefficient (Rac)	Up to the Second day of Cycle 2(each cycle is 28 days)