Back to resultsA Phase I Study of LX-039 Tablets
Primary Purpose
Advanced Breast Cancer
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LX-039 tablets
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Be able to read and sign the informed consent form.
- Adult females (aged ≥18 and ≤75 years).
- Be diagnosed with breast cancer confirmed by pathological examination.
- Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
- Be postmenopausal.
- Subjects who have previously received endocrine therapy and obtained benefit.
- ECOG(Eastern Cooperative Oncology Group) score ≤ 1.
- Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
- Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
- Enough hematology and organ function.
- Expected survival>3 months.
Exclusion Criteria:
- Subjects with HER2-overexpressing breast cancer.
- Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
- Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
- Subjects who received second-line or above chemotherapy.
- Subjects with known allergy to this product or any of its components.
- Subjects who previously used other estrogen receptor down regulators than fulvestrant.
- Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
- Subjects who received cell therapy or tumor vaccine therapy;
- Subjects with severe immunosuppression .
- Severe or uncontrolled disease.
- Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
- Subjects with other malignancy within 5 years prior to study entry.
- Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
- Subjects with history of definite neurological or psychiatric disorders in the past.
- Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
- Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.
Sites / Locations
- Fudan University Shanghai Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part1：dose escalation
Part 2：dose expansion
Arm Description
The investigational product for this study is LX-039 tablets,which can be administered orally. 6~8 ascending dose level until MTD and the specification included 50 mg, 100 mg, 200 mg, 400 mg, 600 mg , 800 mg,1050 mg and 1400 mg. LX-039 tablets will be administered in a therapeutic cycle of 28 days once a day orally. The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
2~3 selected tolerable dose will be selected according to the tolerance and FES PET results of dose escalation phase.The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
Outcomes
Primary Outcome Measures
To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer
Incidence of dose limiting toxicities (DLTs)
Secondary Outcome Measures
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
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Objective response rate (ORR)
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）
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）
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)
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)
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
duration of response (DoR)
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
disease control rate (DCR)
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
clinical benefit rate (CBR)
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
time to progression (TTP)
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
progression-free survival (PFS)
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
overall survival (OS)
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
PK profiles after a single dose of LX-039
Peak Concentration (Cmax)
PK profiles after a single dose of LX-039
Peak Time (Tmax)
PK profiles after a single dose of LX-039
Elimination Half-life (t1/2)
PK profiles after a single dose of LX-039
Eliminate Rate Constant (Kel)
PK profiles after a single dose of LX-039
Mean Residence Time (MRT)
PK profiles after a single dose of LX-039
Area under plasma Concentration-time curve from 0 time to 24 hours (AUC0-24h)
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)
PK profiles after a single dose of LX-039
Area under plasma Concentration-time curve from administration (0) to infinity (AUC0-inf)
PK profiles after a single dose of LX-039
Apparent Total Clearance (CL/F)
PK profiles after a single dose of LX-039
Apparent Volume of Distribution (Vd/F)
PK profiles after continuous administration of LX-039
Trough Concentration at Steady State (Css, min)
PK profiles after continuous administration of LX-039
Peak Concentration at Steady State (Css, max)
PK profiles after continuous administration of LX-039
Average Concentration at Steady State (Css, av)
PK profiles after continuous administration of LX-039
Peak Time (Tss, max)
PK profiles after continuous administration of LX-039
Apparent Volume of Distribution at steady state (Vss/F)
PK profiles after continuous administration of LX-039
Steady-state Clearance Half-life (tss,1/2)
PK profiles after continuous administration of LX-039
Total Body Clearance (CLss/F)
PK profiles after continuous administration of LX-039
Coefficient of Fluctuation (DF)
PK profiles after continuous administration of LX-039
Area under Plasma Concentration-time Curve at Steady State (AUCss)
PK profiles after continuous administration of LX-039
Accumulation Coefficient (Rac)
Full Information
NCT ID
NCT04097756
First Posted
July 29, 2019
Last Updated
April 28, 2023
Sponsor
Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04097756
Brief Title
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
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
January 7, 2020 (Actual)
Primary Completion Date
August 8, 2022 (Actual)
Study Completion Date
February 7, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part1：dose escalation
Arm Type
Experimental
Arm Description
The investigational product for this study is LX-039 tablets,which can be administered orally. 6~8 ascending dose level until MTD and the specification included 50 mg, 100 mg, 200 mg, 400 mg, 600 mg , 800 mg,1050 mg and 1400 mg. LX-039 tablets will be administered in a therapeutic cycle of 28 days once a day orally. The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
Arm Title
Part 2：dose expansion
Arm Type
Experimental
Arm Description
2~3 selected tolerable dose will be selected according to the tolerance and FES PET results of dose escalation phase.The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
Intervention Type
Drug
Intervention Name(s)
LX-039 tablets
Intervention Description
orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, or study termination
Primary Outcome Measure Information:
Title
To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer
Description
Incidence of dose limiting toxicities (DLTs)
Time Frame
DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)
Secondary Outcome Measure Information:
Title
The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer
Description
Number of participants with treatment related. adverse events as assessed by CTCAE v5.0
Time Frame
through study completion,an average of 1 year
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
Objective response rate (ORR)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
proportion of subjects with complete response (CR）
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
proportion of subjects with partial response (PR）
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
proportion of subjects with stable disease (SD)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
proportion of subjects with progressive disease (PD)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
duration of response (DoR)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
disease control rate (DCR)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
clinical benefit rate (CBR)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
time to progression (TTP)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
progression-free survival (PFS)
Time Frame
through study completion，an average of 1 year.
Title
To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.
Description
overall survival (OS)
Time Frame
through study completion，an average of 1 year.
Title
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)
Description
Decrease in SUVmax in comparison with that before treatment
Time Frame
Up to the third day of Cycle 2(each cycle is 28 days)
Title
PK profiles after a single dose of LX-039
Description
Peak Concentration (Cmax)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Peak Time (Tmax)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Elimination Half-life (t1/2)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Eliminate Rate Constant (Kel)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Mean Residence Time (MRT)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Area under plasma Concentration-time curve from 0 time to 24 hours (AUC0-24h)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Area under plasma Concentration-time curve from 0 time to sampling time t of the last measurable concentration (AUC0-last)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Area under plasma Concentration-time curve from administration (0) to infinity (AUC0-inf)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Apparent Total Clearance (CL/F)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after a single dose of LX-039
Description
Apparent Volume of Distribution (Vd/F)
Time Frame
Up to the third day of Cycle 0(Cycle 0 is 7 days)
Title
PK profiles after continuous administration of LX-039
Description
Trough Concentration at Steady State (Css, min)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Peak Concentration at Steady State (Css, max)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Average Concentration at Steady State (Css, av)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Peak Time (Tss, max)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Apparent Volume of Distribution at steady state (Vss/F)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Steady-state Clearance Half-life (tss,1/2)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Total Body Clearance (CLss/F)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Coefficient of Fluctuation (DF)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Area under Plasma Concentration-time Curve at Steady State (AUCss)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
Title
PK profiles after continuous administration of LX-039
Description
Accumulation Coefficient (Rac)
Time Frame
Up to the Second day of Cycle 2(each cycle is 28 days)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be able to read and sign the informed consent form.
Adult females (aged ≥18 and ≤75 years).
Be diagnosed with breast cancer confirmed by pathological examination.
Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
Be postmenopausal.
Subjects who have previously received endocrine therapy and obtained benefit.
ECOG(Eastern Cooperative Oncology Group) score ≤ 1.
Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
Enough hematology and organ function.
Expected survival>3 months.
Exclusion Criteria:
Subjects with HER2-overexpressing breast cancer.
Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
Subjects who received second-line or above chemotherapy.
Subjects with known allergy to this product or any of its components.
Subjects who previously used other estrogen receptor down regulators than fulvestrant.
Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
Subjects who received cell therapy or tumor vaccine therapy;
Subjects with severe immunosuppression .
Severe or uncontrolled disease.
Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
Subjects with other malignancy within 5 years prior to study entry.
Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
Subjects with history of definite neurological or psychiatric disorders in the past.
Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
35436589
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.
Results Reference
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A Phase I Study of LX-039 Tablets
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