Tolerability, Safety, Pharmacokinetics and Efficacy of HS-10241 Single Agent or Combined With Apatinib in Patients With Advanced Solid Tumors (HS:Hansoh;)
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Anticipated)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Yi Li, Ph.D
- Phone Number: 021-68868570
- Email: liuy@shhrp.com
Study Locations
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-
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Chendu, China
- Recruiting
- West China Hospital, Sichuan University
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Contact:
- Feng Bi, Ph.D
- Phone Number: 028-85423203
- Email: bifeng@medmail.com.cn
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 18-75 years of age.
- Histologically or cytologically confirmed advanced or metastatic solid tumor for which standard therapy does not exist, has failed.;For part 2 (Expansion part) c-met immunohistochemistry (IHC) positive(IHC++ or IHC+++)and with at least one measurable disease according to RECIST 1.1.
- No difficulty that may hamper compliance and/or absorption of the tested product (swallowing difficulty, chronic gastrointestinal disease like diarrhea and intestinal obstruction )
- ECOG (Eastern Cooperative Oncology Group) performance status of 0~1.
- Life expectancy of at least 3 months.
- Adequate organ function:(No blood transfusion or hematopoietic stimulating factor within 14days of screening stage):
- Acceptable hematologic status (without hematologic supports including hematopoietic factor, blood transfusion) defined below::Absolute neutrophil count (ANC) ≥1500/μL
- Platelet count ≥90000/μL,,Hemoglobin ≥9.0 g/dL
- Acceptable liver function defined below::Total bilirubin ≤ 1.5 times upper limit of normal range (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times ULN; however, ≤5 times ULN in a subject who has liver metastases.
- Acceptable renal function defined below::Serum creatinine ≤1.5 times ULN or calculated creatinine clearance (by the Cockcroft-Gault formula) ≥60 mL/minutes.
- Acceptable cardiac function defined below:: left ventricular ejection fraction,LVEF≥50% ;normal ECG,QTc male<450ms,female<470ms
- Recovered from toxicities of prior anti-cancer treatment (NCI-CTCAE 4.03≤ grade 1, except alopecia); Proper period of wash out of previous treatment (at least 5 half-life wash out), e.g. No nitrosoureas or mitomycin within 6 weeks,no cytotoxic drugs, monoclonal antibodies, radiation therapy, or surgery within 4 weeks and no endocrine therapy or tyrosine kinase inhibitors (TKIs) within 2 weeks before first dose of the tested product.
- Non-surgical sterilization or post-menopause female must agree to use effective means of contraception (IUD , medication or condom ) during and 8 weeks after the clinical trial.Human Chorionic Gonadotropin ( HCG ) serum test must be negative tested 7 days before the first dose of tested product and not being in the lactation period. For male subjects whose female partners have childbearing potential must be surgical sterilization or agree to use effective means of contraception during and 120 days after the clinical trial.
- Tumor tissue sample available or agree to provide biopsies for testing.
- Volunteer to participate in the clinical trial, understand the procedure of trial and approved informed consent obtained before entering the trial.
Exclusion Criteria:
- Failed in previous c-met or VEGFR inhibitor treatment;
- Participation in other clinical trial or the last dose of the other trail was taken within 4 weeks.
- Other anti-cancer treatment might be received during the trial leading to pause of the trial.
- Tumor infiltration of the vessel, tumor cavity or necrosis with risk of hemorrhage.
- Central nervous system (CNS) metastases or meningeal metastases or primary nervous system tumor untreated by surgery or radiotherapy.
- Patients with clinical symptoms of ascites or pleural effusion, need therapeutic puncture and drainage.
- Uncontrolled chronic systematic complications (such as chronic pulmonary , hepatic, renal or cardiac diseases).
- Grade II myocardial ischemia or myocardial infarction or uncontrolled arrhythmia. Cardiac dysfunction with New York Heart Association (NYHA) Class III or IV.
- Hypertension and unable to be controlled within normal level following treatment of two anti-hypertension agents (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg).
- Urine protein≥ ++,or 24 hour urine protein≥1.0 g;
- Patients with or previous with clinically significant hemorrhage within 3 months, with hemorrhage risk or being in anticoagulant and fibrinolytic treatment like gastrointestinal bleeding , hemorrhagic ulcers, baseline defecate occult blood positive and above or vasculitis. Abnormal coagulant function such as INR(international normalized ratio)>1.5 or PT (Prothrombin Time)>ULN+4 seconds).
- Arterial or venous thromboembolism events within 6 months,like cerebral vascular accident (transient ischemic attack, cerebral hemorrhage or cerebral infarction) or deep venous thrombosis and pulmonary embolism.
- Active infection needed for treatment.
- HIV,HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) positive(HBV:HBsAg positive with hepatic function abnormality and HBV-DNA≧104 copy/mL,HCV:HCV-RNA positive with hepatic function abnormality)needed for antivirus treatment(only for Part 1).
- History of mental or neurological disorders.
- Psychiatric drug abuse history or addiction history
- Unable to complete the trial or withdraw in the middle of the trial due to conditions like psychological state, family relationship, social or geographical factors or with concomitant treatment or abnormal laboratory examinations judging by the investigator.
- Concomitant diseases ( uncontrolled hypertension , severe diabetes and thyroid disease ) deemed by the investigator to be likely to interfere with the subjects safety or leads to discontinuation from the trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: HS-1024+apatinib
For part 1 (PK study) subjects will be given single dose of HS-10241 and then multiple dose of HS-10241 (1 cycle, each cycle 14days) and then HS-10241+aptatinib (each cycle 21 days) until PD. For part 2 (expansion study) subjects will be given HS-10241+aptatinib (each cycle 21 days) until PD (Progression of disease). |
HS-10241 is provided as white, film-coated,immediate release tablets containing HS-10241 at dosage strengths of 20mg/50mg/100 mg.
Multiple tablets of HS-10241 will be administered daily to achieve targeted doses of HS-10241: 200 mg-1200 mg.
Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal.
Other Names:
Apatinib is provided as white, film-coated,immediate release tablets containing aptinib at dosage strengths of 250mg.
Apatinib will be administered daily to achieve targeted doses of 500 mg.
Tablets will be orally administered with 240 ml water, once daily, 1 hour before/after a meal.
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Dose Limiting Toxicities (DLT)
Time Frame: Day1 to day 38 (DLT observation period)
|
To assess MTD and DLT of HS-10241 single agent(D1-D17) then combined with aptatinib (D18-D38) in patients with advanced solid tumors.According to the "3+3" dose escalation design DLT will be determined.
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Day1 to day 38 (DLT observation period)
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|
Maximum Tolerated Dose (MTD)
Time Frame: Day1 to day 38 (DLT observation period)
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One dose level below the dose level determined as DLT will be MTD.
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Day1 to day 38 (DLT observation period)
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Adverse events and Serious Adverse Events
Time Frame: From the day of ICF (Informed Consent Form) until 30 days after the last dose
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To asess the safety of HS-10241 single agent the combined with apatinib in patients with advanced solid tumor.
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From the day of ICF (Informed Consent Form) until 30 days after the last dose
|
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The measurement of maximum plasma concentration (Cmax)
Time Frame: Day 1 to day 38
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Including HS-10241 single dose (D1)/multiple dose of HS-10241(D17) and multiple dose of Apatinib(D38).
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Day 1 to day 38
|
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The measurement of the area under the plasma concentration-time versus time curve(AUC)
Time Frame: Day 1 to day 38
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Area Under Curve(AUC0-t) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38.
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Day 1 to day 38
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The measurement of the area under the plasma concentration-time versus time curve(AUC)
Time Frame: Day 1 to day 38
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AUC(0-inf) will be measured after single dose administration of HS-10241 at day 1.AUC0-t and AUC0-inf are measured after repeated once-daily dose administration of HS-10241 at day 14.AUC0-t and AUC0-inf are measured after repeat once-daily dose administration of apatinib at day 38.
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Day 1 to day 38
|
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The measurement of time of maximum plasma concentration (Tmax)
Time Frame: Day 1 to day 38
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Including HS-10241 single dose (D1)/multiple dose of HS-10241(D17) and multiple dose of apatinib(D38).
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Day 1 to day 38
|
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The measurement of elimination half life (T1/2)
Time Frame: Day 1 to day 38
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T1/2 is measured after single dose administration of HS-10241 at day 1.
T1/2 is measured after repeat once-daily dose administration of HS-10241 at day 17.
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Day 1 to day 38
|
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The Measurement of mean retention time (MRT)
Time Frame: Day 1 to day 38
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MRT is measured after single dose administration of HS-10241 at day 1.
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Day 1 to day 38
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The measurement of apparent volume of distribution (Vd)
Time Frame: Day 1 to day 38
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Vd is measured after single dose administration of HS-10241 at day 1.
Vd is measured after repeated once-daily dose administration of HS-10241 at day 17.
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Day 1 to day 38
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The measurement of clearance (Cl)
Time Frame: Day 1 to day 38
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Vd is measured after single dose administration of HS-10241 at day 1.
Vd is measured after repeated once-daily dose administration of HS-10241 at day 17.
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Day 1 to day 38
|
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Duration of Response Rate
Time Frame: Approximately 1 year
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Determined using RECIST v1.1 criteria
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Approximately 1 year
|
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Progression-Free Survival
Time Frame: Approximately 1 year
|
Determined using RECIST v1.1 criteria
|
Approximately 1 year
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Objective Response Rate
Time Frame: Approximately 1 year
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Determined using RECIST v1.1 criteria
|
Approximately 1 year
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Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Anticipated)
Primary Completion
Study Completion (Anticipated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- HS-10241-I-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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