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Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy Evaluation of GST-HG161

10 januari 2020 bijgewerkt door: Fujian Cosunter Pharmaceutical Co. Ltd

Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy Evaluation of the Selective c-MET Inhibitor GST-HG161 in Patients With Advanced or Metastatic Solid Tumors

Safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy evaluation of the selective c-MET inhibitor GST-HG161 in patients with advanced or metastatic solid tumors: An open, single and multiple administration, dose escalation, and expanded phase I trial

Studie Overzicht

Toestand

Onbekend

Interventie / Behandeling

Gedetailleerde beschrijving

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 .

Studietype

Ingrijpend

Inschrijving (Verwacht)

62

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

    • Shanghai
      • Shanghai, Shanghai, China, 200135
        • Werving
        • Shanghai Oriental Hospital
        • Contact:

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. Voluntarily participate in this study and sign the informed consent;
  2. Aged >=18 years;
  3. 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;
  4. 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;
  5. The investigators evaluate according to RECIST v1.1, subjects must have at least one evaluable focus;
  6. Performance status 0 or 1 based on ECOG scale;
  7. 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;

  8. Expected survival time>=12 weeks;
  9. 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;
  10. Subjects or their legal representatives are able to communicate well with the investigators and complete the study in accordance with protocol.

Exclusion Criteria:

  1. 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;
  2. 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;
  3. Digestive tract disorder that affect clinical trials, such as: Intractable hiccups, nausea, emesis, etc.; Chronic digestive diseases: Crohn's disease, ulcerative colitis, etc.; Dysphagia;
  4. 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;
  5. Pregnant or lactating women;
  6. 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;
  7. The adverse reactions of previous anti-tumor treatments have not recovered to CTCAE 5.0 level<=1 (except for hair loss);
  8. Participated in other clinical trials as a subject within 4 weeks prior to this study;
  9. The investigators determine ineligible to participate in the clinical trial for other reasons.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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 .
Andere namen:
  • selected C-MET Inhibitor

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
DLT (Dose-Limiting Toxicity)
Tijdsspanne: Up to 27 days
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.
Up to 27 days
MTD (Maximum Tolerated Dose)
Tijdsspanne: Up to 27 days
MTD was defined as the dose level at which 1 out of 6 subjects or no one experienced a DLT.
Up to 27 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Area Under Curve (AUC)
Tijdsspanne: 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.
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.
Peak Plasma Concentration (Cmax)
Tijdsspanne: 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.
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.
Cl/F
Tijdsspanne: 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.
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.
T1/2
Tijdsspanne: 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.
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.
ORR
Tijdsspanne: 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
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)
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
PFS
Tijdsspanne: 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
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.
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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Hoofdonderzoeker: JI LI, PHD, Shanghai Oriental Hospital ,China

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 juli 2019

Primaire voltooiing (Verwacht)

30 september 2020

Studie voltooiing (Verwacht)

31 december 2020

Studieregistratiedata

Eerst ingediend

7 januari 2020

Eerst ingediend dat voldeed aan de QC-criteria

10 januari 2020

Eerst geplaatst (Werkelijk)

14 januari 2020

Updates van studierecords

Laatste update geplaatst (Werkelijk)

14 januari 2020

Laatste update ingediend die voldeed aan QC-criteria

10 januari 2020

Laatst geverifieerd

1 januari 2020

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • GST-HG161-I

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

Nee

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op Vaste tumor

Klinische onderzoeken op GST-HG161

3
Abonneren