A Phase I Study of LX-039 Tablets

Shandong Luoxin Pharmaceutical Group

Status and phase: Completed; Phase 1

Conditions: Advanced Breast Cancer

Treatments: Drug: LX-039 tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT04097756

OE861801

Details and patient eligibility

About

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.

Enrollment: 44 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups

Part1：dose escalation

Experimental group

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.

Treatment:

Drug: LX-039 tablets

Part 2：dose expansion

Experimental group

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.

Treatment:

Drug: LX-039 tablets