A Phase I Study of LX-039 Tablets

April 28, 2023 updated by: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
through study completion,an average of 1 year
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)
through study completion，an average of 1 year.
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）
through study completion，an average of 1 year.
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）
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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)
through study completion，an average of 1 year.
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
Up to the third day of Cycle 2(each cycle is 28 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the third day of Cycle 0(Cycle 0 is 7 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)
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)
Up to the Second day of Cycle 2(each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 7, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 8, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 7, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 20, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 1, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OE861801

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Breast Cancer

Clinical Trials on LX-039 tablets

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings