A Study of WXFL10030390 in Patients With Advanced Solid Tumors or Lymphoma

April 17, 2023 updated by: Shanghai Jiatan Pharmatech Co., Ltd

A Phase Ⅰ Study of PI3K/mTOR Dual Inhibitor WXFL10030390 to Evaluate the Safety, Tolerability and Pharmacokinetics in Patients With Advanced Solid Tumors or Lymphoma

WXFL10030390 (WX390) is a novel oral small molecular that inhibits phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) and has demonstrated potent inhibitory effects on multiple human tumor xenografts. The first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of WX390 at single dose and multiple doses.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will be an open-lable, phase Ⅰ study and will evaluate the safety and pharmacokinetics of WX390 after a single administration followed by a 28-day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-lable administration of WX390 at the MTD.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • 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

      • Shanghai, China
        • Shanghai East Hospital

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

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥18 and ≤75 years of age
  • Histological or cytological confirmed advanced solid tumor or lymphoma, standard regimen failed or no standard regimen available
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Life expectancy of more than 3 months
  • At least one measurable lesion according to RECIST 1.1 or Lugano 2014
  • Adequate organic function: Absolute neutrophil count (ANC) ≥2.0×109/L,PLT≥100×109/L,Hb≥9g/L hepatic function:TBIL≤1.5×upper limit of normal (ULN),Alanine aminotransferase (ALT) ≤2.5×ULN,aspartate aminotransferase (AST) ≤2.5×ULN; renal function:Cr≤1.5×ULN and>50ml/min; coagulation function: APTT≤1.5 ×ULN,PT≤1.5 ×ULN, INR≤1.5 ×ULN; GLU<7mmol/L and HbA1C<7%; TG≤1.5×ULN,CHOL≤1.5×ULN
  • Subjects who have the fertility should agree to use reliable contraceptive methods during this study and subsequently at least 12 weeks after the last administration; for female subjects, the blood pregnancy test should be negative within 7 days prior to the enrollment
  • Signed and dated informed consent

Exclusion Criteria:

  • Anti-cancer therapy within 4 weeks prior to the initiation of investigational treatment
  • Surgery within 4 weeks prior to the initiation of study treatment
  • Use of strong inducers or inhibitors of CYP3A4 within 1 weeks before the first dose of study treatment. See Appendix 5 for a list of such medications
  • Received corticosteroids treatment or other immunodepressant within 2 weeks before the first dose of study treatment
  • Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for alopecia)
  • Patients with clinical symptomatic brain metastases, spinal compression, meningitis carcinomatosa or other evidence that shows uncontrolled brain or spinal metastases
  • Previous treatment with PI3K/mTOR inhibitors
  • Patients who once or being suffer Interstitial lung disease
  • Evidence of ongoing or active infection
  • History of human immunodeficiency virus (HIV) infection
  • History of hepatitis B or C infection
  • Clinically significant cardiovascular disease, including but not limited to acute coronary syndrome, congestive heart-failure, cerebral stroke within 6 months prior to enrollment, New York Heart Association Class ≥II cardiac functional grading or left ventricular ejection fraction (LVEF) < 50%
  • Inability to take medication orally
  • Severe gastrointestinal disease leading to diarrhea
  • Diabetics receiving insulin treatment
  • Patients with active autoimmune disease (including systemic lupus erythematosus, rheumatoid arthritis, nodular vasculitis)
  • Abuse of alcohol or drugs
  • People with cognitive and psychological abnormality or with low compliance
  • Pregnant or lactating women
  • Researchers believe that subjects may not be able to complete the study or may not be able to comply with the requirements of this study

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: WXFL10030390 tablet

WXFL10030390 continuous oral dosing (0.1 mg once a day)

WXFL10030390 continuous oral dosing (0.2 mg once a day)

WXFL10030390 continuous oral dosing (0.4 mg once a day)

WXFL10030390 continuous oral dosing (0.7 mg once a day)

WXFL10030390 continuous oral dosing (1.1 mg once a day)

WXFL10030390 continuous oral dosing (1.4 mg once a day)

WXFL10030390 continuous oral dosing (1.7 mg once a day)

WXFL10030390 is a tablet in the form of 0.1mg and 0.5mg, oral, once a day.
Other Names:
  • WX390

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Time Frame: From first dose to within 30 days after the last dose
The safety and tolerability of WXFL10030390 will be evaluated based on adverse events data. Other safety parameters include physical examination, clinical laboratory tests including coagulation function, renal function, hepatic function, blood glucose and blood lipid.
From first dose to within 30 days after the last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (Cmax)
Time Frame: 28 days
Cmax will be determined for an oral administration of WXFL10030390 tablets.
28 days
Time to reach plasma Cmax (tmax)
Time Frame: 28 days
tmax will be determined for an oral administration of WXFL10030390 tablets.
28 days
Area under the plasma concentration-time curve (AUC)
Time Frame: 28 days
AUC will be determined for an oral administration of WXFL10030390 tablets.
28 days
Terminal elimination half-life (t½)
Time Frame: 28 days
t½ will be determined for an oral administration of WXFL10030390 tablets.
28 days
Recommended study Phase II dose (RP2D)
Time Frame: Up to 1 year
The recommended phase 2 dose (RP2D) of WXFL10030390 will be determined based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.
Up to 1 year
Disease control rate
Time Frame: From first dose to within 30 days after the last dose
The sum of complete responses (CR) + partial responses (PR) + stable disease (SD) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Lugano 2014 criteria
From first dose to within 30 days after the last dose
Objective response rate
Time Frame: From first dose to within 30 days after the last dose
Defined as complete response [CR] + partial response [PR]) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Lugano 2014 criteria
From first dose to within 30 days after the last dose

Collaborators and Investigators

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

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)

October 25, 2018

Primary Completion (Actual)

July 25, 2020

Study Completion (Actual)

July 25, 2020

Study Registration Dates

First Submitted

October 21, 2018

First Submitted That Met QC Criteria

November 1, 2018

First Posted (Actual)

November 5, 2018

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 17, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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