Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy Evaluation of GST-HG161
Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy Evaluation of the Selective c-MET Inhibitor GST-HG161 in Patients With Advanced or Metastatic Solid Tumors
調査の概要
詳細な説明
This is a phase I trial to evaluate safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy GST-HG161.
There are 7 dose cohorts, including60mg, 150mg, 300mg, 450mg, 600mg, 750mg, 900mg QD in the dose escalation stage and GST-HG161 will be administered orally to patients once daily for each dose cohort. Recommended protocal in the dose expansion stage will be determined by the results in the dose escalation stage .
研究の種類
入学 (予想される)
段階
- フェーズ 1
連絡先と場所
研究場所
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Shanghai
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Shanghai、Shanghai、中国、200135
- 募集
- Shanghai Oriental Hospital
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コンタクト:
- JI LI, Professor
- 電話番号:+86 021-38804518
- メール:lijin@csco.org.cn
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Voluntarily participate in this study and sign the informed consent;
- Aged >=18 years;
- Patients with advanced or metastatic solid tumors diagnosed histologically or cytologically, and no approved standard treatment regimen or no efficacy or intolerance to standard treatment regimen;
- Patients with solid tumors confirmed c-Met positive by testing. The definition of c-Met positive is: 1) IHC expression of c-Met (positive criteria : 1+ and above); 2) FISH amplification of c-Met (positive criteria: Ratio>=1.8), any positive of the above two methods can be enrolled into the group;
- The investigators evaluate according to RECIST v1.1, subjects must have at least one evaluable focus;
- Performance status 0 or 1 based on ECOG scale;
Adequate bone marrow and major organ functions:
Bone marrow: Hemoglobin>=9.0 g/dL, absolute count of neutrophils>1.5x10^9/L, platelet≥75x10^9/L; Coagulation function: Prothrombin time (PT)<=1.5 ULN, international normalized ratio (INR)<=1.5 ULN; Hepatic function: Total bilirubin<=1.5 ULN, ALT<=2.5 ULN, AST<=2.5 ULN; For patients with hepatic metastases or hepatoma, total bilirubin<=2 ULN, ALT<=5 ULN, AST<=5 ULN are allowed; Renal function: Serum creatinine<1.5 ULN, creatinine clearance rate>50mL/min; Other laboratory inspection indexes: Lipase 1.5 ULN, amylase<1.5 ULN, albumin>=28g/L;
- Expected survival time>=12 weeks;
- Fertile men and women must agree to carry out birth control with effective methods for a period of 180 days from the signing of the informed consent form until the last administration of investigational drug. Fertile women include premenopausal women and women 2 years before menopause. Fertile women must have a negative pregnancy test within 7 days (including) before the first dose of the investigational drug;
- Subjects or their legal representatives are able to communicate well with the investigators and complete the study in accordance with protocol.
Exclusion Criteria:
- Patients with clinical symptoms of brain metastasis, spinal cord compression, carcinomatous meningitis, or other evidence showing that the brain or spinal cord metastasis has not been controlled, and patients not suitable for the group judged by the investigators;
- Obvious basic cardiovascular diseases, including the following conditions: Prolonged QT/QTcF interval in baseline ECG (QTcF >480ms); Severe abnormalities in baseline ECG, including rhythm, conduction, and form. For example, complete left bundle branch block, degree III atrioventricular block, etc.; Cardiovascular abnormalities identified within 6 months, such as myocardial infraction, arrhythmia, angina, angioplasty, stent implantation, coronary artery bridging, congestive heart failure, etc.; Left ventricular ejection fraction is lower than the minimum normal value showed by cardiac ultrasound; Uncontrolled hypotension or uncontrolled hypertension;
- Digestive tract disorder that affect clinical trials, such as: Intractable hiccups, nausea, emesis, etc.; Chronic digestive diseases: Crohn's disease, ulcerative colitis, etc.; Dysphagia;
- Patients with a history of other serious underlying diseases, such as: A definite history of neurological or psychiatric disorders, including epilepsy or dementia; Patients with active hepatitis B (HBV-DNA>1000 copy number/mL), or hepatitis C virus antibody or HCV-RNA positive, or infected with human immunodeficiency virus (HIV); A history of organ transplantation; Severe infection;
- Pregnant or lactating women;
- Received chemotherapy, radiation therapy, hormonal therapy, biological therapy or other anti-tumor treatment within 4 weeks (from the last medication of mitomycin and nitrosoureas for at least 6 weeks, from the last medication of fluorouracil oral drugs, such as Tegafur, Capecitabine for at least 2 weeks), or the treatment is still within 5 half-life period;
- The adverse reactions of previous anti-tumor treatments have not recovered to CTCAE 5.0 level<=1 (except for hair loss);
- Participated in other clinical trials as a subject within 4 weeks prior to this study;
- The investigators determine ineligible to participate in the clinical trial for other reasons.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的:GST-HG161
There are 7 dose cohorts, including60mg, 150mg, 300mg, 450mg, 600mg, 750mg, 900mg QD in the dose escalation stage and GST-HG161 will be administered orally to patients once daily for each dose cohort.
Recommended dose in the dose expansion stage will be determined by the results in the dose escalation stage .
|
There are 7 dose cohorts, including60mg, 150mg, 300mg, 450mg, 600mg, 750mg, 900mg QD in the dose escalation stage and GST-HG161 will be administered orally to patients once daily for each dose cohort.
Recommended dose in the dose expansion stage will be determined by the results in the dose escalation stage .
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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DLT (Dose-Limiting Toxicity)
時間枠:Up to 27 days
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DLT was defined as one of the following adverse events (AEs) observed in 27 days: Grade 4 hematologic AE; Grade >=3 febrile neutropenia; Grade 3 thrombocytopenia with bleeding; Grade >=3 nausea, emesis, diarrhea and constipation, despite optimal treatment; Grade >=3 non-hematological AE.
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Up to 27 days
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MTD (Maximum Tolerated Dose)
時間枠:Up to 27 days
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MTD was defined as the dose level at which 1 out of 6 subjects or no one experienced a DLT.
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Up to 27 days
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Area Under Curve (AUC)
時間枠:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
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Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Peak Plasma Concentration (Cmax)
時間枠:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
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Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Cl/F
時間枠:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
|
Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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T1/2
時間枠:Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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Plasma samples were collected at different points for pharmacokinetic analysis
|
Measured on 0,1, 2, 4, 6, 8, 12, 24 and 48 hours in single-dosing stage and pre-administration of day 6, day 13, day 20 and 0, 2, 4, 6, 8,12 and 24 hours of Day27 in the multiple-dosing stage.
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ORR
時間枠:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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Objective response rate (ORR) is defined as the proportion of subjects with complete or partial response as determined by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
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From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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PFS
時間枠:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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PFS(Progression-Free-Survival) was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever came first.
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From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months
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協力者と研究者
捜査官
- 主任研究者:JI LI, PHD、Shanghai Oriental Hospital ,China
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- GST-HG161-I
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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