A Phase I Study of LX-039 Tablets
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part1：dose escalation 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. |
Drug: LX-039 tablets
orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, or study termination
|
| Experimental: Part 2：dose expansion 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. |
Drug: LX-039 tablets
orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, or study termination
|
Outcome Measures
Primary Outcome Measures
- To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer [DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)]
Incidence of dose limiting toxicities (DLTs)
Secondary Outcome Measures
- The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer [through study completion,an average of 1 year]
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. [through study completion，an average of 1 year.]
Objective response rate (ORR)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1. [through study completion，an average of 1 year.]
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. [through study completion，an average of 1 year.]
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. [through study completion，an average of 1 year.]
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. [through study completion，an average of 1 year.]
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. [through study completion，an average of 1 year.]
duration of response (DoR)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1. [through study completion，an average of 1 year.]
disease control rate (DCR)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1. [through study completion，an average of 1 year.]
clinical benefit rate (CBR)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1. [through study completion，an average of 1 year.]
time to progression (TTP)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1. [through study completion，an average of 1 year.]
progression-free survival (PFS)
- To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1. [through study completion，an average of 1 year.]
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) [Up to the third day of Cycle 2(each cycle is 28 days)]
Decrease in SUVmax in comparison with that before treatment
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Peak Concentration (Cmax)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Peak Time (Tmax)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Elimination Half-life (t1/2)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Eliminate Rate Constant (Kel)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Mean Residence Time (MRT)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Area under plasma Concentration-time curve from 0 time to 24 hours (AUC0-24h)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
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 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Area under plasma Concentration-time curve from administration (0) to infinity (AUC0-inf)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Apparent Total Clearance (CL/F)
- PK profiles after a single dose of LX-039 [Up to the third day of Cycle 0(Cycle 0 is 7 days)]
Apparent Volume of Distribution (Vd/F)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Trough Concentration at Steady State (Css, min)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Peak Concentration at Steady State (Css, max)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Average Concentration at Steady State (Css, av)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Peak Time (Tss, max)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Apparent Volume of Distribution at steady state (Vss/F)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Steady-state Clearance Half-life (tss,1/2)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Total Body Clearance (CLss/F)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Coefficient of Fluctuation (DF)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Area under Plasma Concentration-time Curve at Steady State (AUCss)
- PK profiles after continuous administration of LX-039 [Up to the Second day of Cycle 2(each cycle is 28 days)]
Accumulation Coefficient (Rac)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Be able to read and sign the informed consent form.
-
Adult females (aged ≥18 and ≤75 years).
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Be diagnosed with breast cancer confirmed by pathological examination.
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Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
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Be postmenopausal.
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Subjects who have previously received endocrine therapy and obtained benefit.
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ECOG(Eastern Cooperative Oncology Group) score ≤ 1.
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Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
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Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
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Enough hematology and organ function.
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Expected survival>3 months.
Exclusion Criteria:
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Subjects with HER2-overexpressing breast cancer.
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Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
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Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
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Subjects who received second-line or above chemotherapy.
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Subjects with known allergy to this product or any of its components.
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Subjects who previously used other estrogen receptor down regulators than fulvestrant.
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Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
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Subjects who received cell therapy or tumor vaccine therapy;
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Subjects with severe immunosuppression .
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Severe or uncontrolled disease.
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Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
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Subjects with other malignancy within 5 years prior to study entry.
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Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
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Subjects with history of definite neurological or psychiatric disorders in the past.
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Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
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Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fudan University Shanghai Cancer Center | Shanghai | Shanghai | China | 200032 |
Sponsors and Collaborators
- Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OE861801