A Study of LXI-15029 in Patients With Advanced Malignant Solid Tumors

NCT03125746 | Unknown Phase 1

• 1 other identifier: OE861501
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

1\. To evaluate the safety and tolerability of LXI-15029 in Chinese patients with advanced malignant solid tumors in monotherapy period, including confirmation of the maximum tolerated dose (MTD) of monotherapy. 2.To evaluate the safety and tolerability of LXI-15029 in Chinese postmenopausal patients with metastatic or locally advanced breast cancer with estrogen receptor (+) and human epidermal growth factor receptor 2 (-) in combined with Exemestane period , including confirmation of the maximum tolerated dose(MTD) of the combined therapy with Exemestane.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events

  To evaluate the safety and tolerability of LXI-15029 through evaluation of the incidence and severity of adverse event (Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE, 4.03))

  When subject complete 1 cycle (28 days) treatment with safety and tolerability assessment by investigators.

Secondary Outcomes (3)

• Maximum Concentration (Cmax)

  When subject complete 1 cycle (28 days) treatment

• Area Under the Curve (AUC)

  When subject complete 1 cycle (28 days) treatment

• Tmax

  When subject complete 1 cycle (28 days) treatment

Other Outcomes (2)

• Best objective response

  Estimated to be up to 6 months

• Progression-free survival (PFS)

  Estimated to be up to 6 months

Study Arms (2)

LXI-15029

EXPERIMENTAL

Drug: LXI-15029

LXI-15029+Exemestane

EXPERIMENTAL

Drug: LXI-15029+Exemestane

Interventions

LXI-15029 DRUG

The investigational product for this study is LXI-15029 capsule, which can be administered orally and the specification included 10 mg and 50 mg. There will be about 6 cohorts during the monotherapy period. LXI-15029 capsules will be administered in a therapeutic cycle of 28 days twice a day orally. The patients will be given LXI-15029 continuously, in a therapeutic cycle of 28 days. Patients will continue therapy with LXI-15029 if good safety and tolerability were assessed by investigators after 1 cycle treatment. The treatment will continue until progression or occurrence of unmanageable toxicity.

LXI-15029

LXI-15029+Exemestane DRUG

The combined drug in the combined therapy period of this study (investigational product) is Exemestane tablet (specification 25 mg). Exemestane should be taken at similar time every day in case of multiple doses (Cycle 1 Day 1 to Cycl 1 Day 28). If one dose was missed (e.g., forgetting, vomiting, etc.), this dose could not be made up and should be administered at next scheduled time point. And the dose of LXI-15029 will be determinated by safety review committee after dose escalation

LXI-15029+Exemestane

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Monotherapy Period
• Patients with signed written informed consent form;
• Chinese man or woman, aged 18 to 65 years old;
• Patient with histologically or cytologically confirmed, advanced solid tumor after failure of standard of care or without standard of care;
• Patients must have at least one measurable lesion as defined by RECIST v1.1 (during dose escalation phase,no measurable lesion as defined by RECIST v1.1 but evaluable lesion could also been enrolled);
• Expected survival no less than 12 weeks;
• Eastern Cooperative Oncology Group (USA) Performance Status 0 to 1;
• Patient of childbearing potential (regardless of man or woman) who is willing to take contraceptive measures from signature of the informed consent form to 3 months after the last dose of investigational product. Negative serum pregnancy test within 7 days prior to the planned first dose of investigational product for female patient of childbearing potential;
• Have the ability to communicate with study staff, understand and comply with all the study requirements;
• Combined with Exemestane period
• Patients with signed written informed consent form;
• Chinese patients aged postmenopausal women to 65 years old;
• Postmenopausal patient;
• Histologically or cytologically confirmed metastatic or locally advanced breast cancer that is not suitable for surgery or radiotherapy;
• Estrogen receptor (+), defined as tumor cells with estrogen receptor (+) ≥1% in immunohistochemistry;

You may not qualify if:

• Monotherapy Period:
• Previous antitumor therapy or any surgical operation within 4 weeks prior to administration of the first dose of study drug;
• Treatment with myeloid hematopoietic growth factor within 2 weeks prior to use of investigational product;
• Patients receiving corticosteroids or immunosuppressive agents within 4 weeks prior to administration of the first dose of study drug;
• Use of potent-to-moderate cytochrome metabolism enzyme CYP3A4 inhibitor and inducer prior to treatment or during washout period;
• Known allergy to LXI-15029 or similar products (mammalian target of rapamycin (mTOR) inhibitor or dual mTOR inhibitor) or other components of LXI-15029;
• Previous or receiving of PI3K or mTOR inhibitors (e.g., BKM120, everolimus, AZD8055 or AZD2014, etc.);
• History, symptoms or signs of spinal compression, brain metastasis or meningeal metastasis, or manifestations of edema or progression in radiology;
• History of other tumors within 5 years, except cured carcinoma in situ of cervix or cutaneous basal cell carcinoma;
• The toxicity induced by treatment unable to be recovered or stabilized to grade 1 or below except alopecia (common terminology criteria on adverse event version 4.03 (CTCAE 4.03));
• Hemotology and coagulation abnormal defined in protocol;
• Hepatic function abnormal defined in protocol;
• Renal function abnormal defined in protocol;
• Cholesterol \> 300 mg/dl or 7.75 mmol/L, and/or triglyceride \> 2.5 × ULN;
• Previous history of type 1 or 2 diabetes, or abnormal fasting blood glucose \>126 mg/dL(\>7 mmol/L) at screening;

Sponsors & Collaborators

• Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

Related Publications (2)

• Wang J, Gui L, Mu Y, Wang J, Chi Y, Liu Z, Li Q, Xu B. Phase I dose escalation study and pilot efficacy analysis of LXI-15029, a novel mTOR dual inhibitor, in Chinese subjects with advanced malignant solid tumors. BMC Cancer. 2023 Dec 6;23(1):1200. doi: 10.1186/s12885-023-11578-8.

  PMID: 38057772 DERIVED

• Zhang Q, Zhang Y, Chen Y, Qian J, Zhang X, Yu K. A Novel mTORC1/2 Inhibitor (MTI-31) Inhibits Tumor Growth, Epithelial-Mesenchymal Transition, Metastases, and Improves Antitumor Immunity in Preclinical Models of Lung Cancer. Clin Cancer Res. 2019 Jun 15;25(12):3630-3642. doi: 10.1158/1078-0432.CCR-18-2548. Epub 2019 Feb 22.

  PMID: 30796032 DERIVED

Central Study Contacts

Wenliang Wang, Master

CONTACT

86-21-61060190; wenliangwang@luoxinbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 24, 2017
• Study Start: June 12, 2017
• Primary Completion: October 28, 2021
• Study Completion: October 28, 2021
• Last Updated: January 5, 2021

Record last verified: 2020-12

Locations

CN (1)