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Completed

NCT Number: NCT04097756

A Phase I Study of LX-039 Tablets

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.

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Key information

Conditions

Advanced Breast Cancer

Age range

18 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LX-039 tablets

Drug

orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, or study termination

Primary outcomes

  1. 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)

    Incidence of dose limiting toxicities (DLTs)

Secondary outcomes

  1. The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer

    Time frame: through study completion,an average of 1 year

    Number of participants with treatment related. adverse events as assessed by CTCAE v5.0

  2. 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.

    Objective response rate (ORR)

  3. 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.

    proportion of subjects with complete response (CR）

  4. 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.

    proportion of subjects with partial response (PR）

  5. 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.

    proportion of subjects with stable disease (SD)

  6. 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.

    proportion of subjects with progressive disease (PD)

  7. 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.

    duration of response (DoR)

  8. 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.

    disease control rate (DCR)

  9. 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.

    clinical benefit rate (CBR)

  10. 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.

    time to progression (TTP)

  11. 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.

    progression-free survival (PFS)

  12. 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.

    overall survival (OS)

  13. 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)

    Decrease in SUVmax in comparison with that before treatment

  14. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Peak Concentration (Cmax)

  15. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Peak Time (Tmax)

  16. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Elimination Half-life (t1/2)

  17. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Eliminate Rate Constant (Kel)

  18. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Mean Residence Time (MRT)

  19. PK profiles after a single dose of LX-039

    Time frame: 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)

  20. PK profiles after a single dose of LX-039

    Time frame: 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)

  21. PK profiles after a single dose of LX-039

    Time frame: 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)

  22. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Apparent Total Clearance (CL/F)

  23. PK profiles after a single dose of LX-039

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

    Apparent Volume of Distribution (Vd/F)

  24. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Trough Concentration at Steady State (Css, min)

  25. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Peak Concentration at Steady State (Css, max)

  26. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Average Concentration at Steady State (Css, av)

  27. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Peak Time (Tss, max)

  28. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Apparent Volume of Distribution at steady state (Vss/F)

  29. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Steady-state Clearance Half-life (tss,1/2)

  30. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Total Body Clearance (CLss/F)

  31. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Coefficient of Fluctuation (DF)

  32. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Area under Plasma Concentration-time Curve at Steady State (AUCss)

  33. PK profiles after continuous administration of LX-039

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

    Accumulation Coefficient (Rac)

Sponsors and collaborators

Lead sponsor

Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

Industry

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2022
Study completion
2023
First posted
Sep 20, 2019
Registry last updated
May 1, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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