Clinical trial NCT03730142: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: phosphoinositide-3 kinase (PI3K)
mammalian target of rapamycin (mTOR)
Lead sponsor: Shanghai Jiatan Pharmatech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2018-11-05
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse Events evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0
timeFrame: From first dose to within 30 days after the last dose
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 days
measure: Time to reach plasma Cmax (tmax)
timeFrame: 28 days
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 28 days
measure: Terminal elimination half-life (t½)
timeFrame: 28 days
measure: Recommended study Phase II dose (RP2D)
timeFrame: Up to 1 year
measure: Disease control rate
timeFrame: From first dose to within 30 days after the last dose
measure: Objective response rate
timeFrame: From first dose to within 30 days after the last dose
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
Study officials:
affiliation: Shanghai East Hospital
name: Jin Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: