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

Primary Purpose

Advanced Cancer

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
WXFL10030390
Sponsored by
Shanghai Jiatan Pharmatech Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Cancer focused on measuring phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Shanghai East Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

WXFL10030390 tablet

Arm Description

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)

Outcomes

Primary Outcome Measures

Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0
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.

Secondary Outcome Measures

Maximum plasma concentration (Cmax)
Cmax will be determined for an oral administration of WXFL10030390 tablets.
Time to reach plasma Cmax (tmax)
tmax will be determined for an oral administration of WXFL10030390 tablets.
Area under the plasma concentration-time curve (AUC)
AUC will be determined for an oral administration of WXFL10030390 tablets.
Terminal elimination half-life (t½)
t½ will be determined for an oral administration of WXFL10030390 tablets.
Recommended study Phase II dose (RP2D)
The recommended phase 2 dose (RP2D) of WXFL10030390 will be determined based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.
Disease control rate
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
Objective response rate
Defined as complete response [CR] + partial response [PR]) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Lugano 2014 criteria

Full Information

First Posted
October 21, 2018
Last Updated
April 17, 2023
Sponsor
Shanghai Jiatan Pharmatech Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT03730142
Brief Title
A Study of WXFL10030390 in Patients With Advanced Solid Tumors or Lymphoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 25, 2018 (Actual)
Primary Completion Date
July 25, 2020 (Actual)
Study Completion Date
July 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Jiatan Pharmatech Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Cancer
Keywords
phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
WXFL10030390 tablet
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
WXFL10030390
Other Intervention Name(s)
WX390
Intervention Description
WXFL10030390 is a tablet in the form of 0.1mg and 0.5mg, oral, once a day.
Primary Outcome Measure Information:
Title
Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Description
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.
Time Frame
From first dose to within 30 days after the last dose
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax)
Description
Cmax will be determined for an oral administration of WXFL10030390 tablets.
Time Frame
28 days
Title
Time to reach plasma Cmax (tmax)
Description
tmax will be determined for an oral administration of WXFL10030390 tablets.
Time Frame
28 days
Title
Area under the plasma concentration-time curve (AUC)
Description
AUC will be determined for an oral administration of WXFL10030390 tablets.
Time Frame
28 days
Title
Terminal elimination half-life (t½)
Description
t½ will be determined for an oral administration of WXFL10030390 tablets.
Time Frame
28 days
Title
Recommended study Phase II dose (RP2D)
Description
The recommended phase 2 dose (RP2D) of WXFL10030390 will be determined based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.
Time Frame
Up to 1 year
Title
Disease control rate
Description
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
Time Frame
From first dose to within 30 days after the last dose
Title
Objective response rate
Description
Defined as complete response [CR] + partial response [PR]) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Lugano 2014 criteria
Time Frame
From first dose to within 30 days after the last dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Li, Doctor
Organizational Affiliation
Shanghai East Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai East Hospital
City
Shanghai
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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

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