Clinical Trials /

A Phase I Study of LX-039 Tablets

NCT04097756

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Enrolling by invitation

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: OE861801
  • NCT ID: NCT04097756

Conditions

  • Advanced Breast Cancer

Interventions

DrugSynonymsArms
LX-039 tabletsPart1:dose escalation

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part1:dose escalationExperimentalThe 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.
  • LX-039 tablets
Part 2:dose expansionExperimental2~3 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.
  • LX-039 tablets

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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:To explore the tolerance of LX-039 in ER +, HER2 − patients with advanced breast cancer
Time Frame:DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)
Safety Issue:
Description:Incidence of dose limiting toxicities (DLTs)

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

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