Phase II Trial of HM61713 for the Treatment of ≥2nd Line T790M Mutation Positive Adenocarcinoma of the Lung
A Single Arm, Open-label, Phase 2 Study Evaluating the Efficacy, Safety and PK of HM61713 in Patients With T790M-positive NSCLC After Treatment With an Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Darlinghurst, Austrálie
- Research Site
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Fitzroy, Austrálie
- Research Site
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Frankston, Austrálie
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Kogarah, Austrálie
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St Albans, Austrálie
- Research Site
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Woolloongabba, Austrálie
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Cebu, Filipíny
- Research Site
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Kalakhang Maynila
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Makati, Kalakhang Maynila, Filipíny
- Research Site
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Manila
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Pasig, Manila, Filipíny
- Research Site
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Metro Manila
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Manila, Metro Manila, Filipíny
- Research Site 2
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Manila, Metro Manila, Filipíny
- Research Site
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Bergamo, Itálie
- Research Site
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Bologna, Itálie
- Research Site
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Catania, Itálie
- Research Site
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Milano, Itálie
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Rome, Itálie
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Toronto, Kanada
- Research Site
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Cheongju-si, Korejská republika
- Research Site
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Goyang-si, Korejská republika
- Research Site
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Hwasun, Korejská republika
- Research Site
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Incheon, Korejská republika
- Research Site
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Seongnam-si, Korejská republika
- Research Site 2
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Seongnam-si, Korejská republika
- Research Site
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Seoul, Korejská republika
- Research Site
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Seoul, Korejská republika
- Research Site 2
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Seoul, Korejská republika
- Research Site 3
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Seoul, Korejská republika
- Research Site 4
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Seoul, Korejská republika
- Research Site 5
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Seoul, Korejská republika
- Research Site 6
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Seoul, Korejská republika
- Research Site 7
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Seoul, Korejská republika
- Research Site 8
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Kuala Lumpur, Malajsie
- Research Site
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Kuantan, Malajsie
- Research Site
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Kuching, Malajsie
- Research Site
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Penang
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George Town, Penang, Malajsie
- Research Site
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Berlin, Německo
- Research Site
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Homburg, Německo
- Research Site
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Leipzig, Německo
- Research Site
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München, Německo
- Research Site
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Ulm, Německo
- Research Site
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California
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Beverly Hills, California, Spojené státy
- Research Site
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Burbank, California, Spojené státy
- Research Site
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Los Angeles, California, Spojené státy
- Research Site
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Los Angeles, California, Spojené státy
- Research Site 2
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Montebello, California, Spojené státy
- Research Site
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Orange, California, Spojené státy
- Research Site
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San Diego, California, Spojené státy
- Research Site
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Florida
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Boca Raton, Florida, Spojené státy
- Research Site
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Hawaii
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Honolulu, Hawaii, Spojené státy
- Research Site
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Illinois
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Evanston, Illinois, Spojené státy
- Research Site
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Maryland
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Bethesda, Maryland, Spojené státy
- Research Site
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Massachusetts
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Boston, Massachusetts, Spojené státy
- Research Site
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New Hampshire
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Lebanon, New Hampshire, Spojené státy
- Research Site
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North Carolina
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Charlotte, North Carolina, Spojené státy
- Research Site
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Washington
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Washington, Washington, Spojené státy
- Research Site
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Kaohsiung, Tchaj-wan
- Research Site
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Taichung, Tchaj-wan
- Research Site
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Tainan, Tchaj-wan
- Research Site
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Tainan, Tchaj-wan
- Research Site 2
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Taipei, Tchaj-wan
- Research Site
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Taipei, Tchaj-wan
- Research Site 2
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Barcelona, Španělsko
- Research Site
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Barcelona, Španělsko
- Research Site 2
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Barcelona, Španělsko
- Research Site 3
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Barcelona, Španělsko
- Research Site 4
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La Coruna, Španělsko
- Research Site
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Madrid, Španělsko
- Research Site
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Madrid, Španělsko
- Research Site 2
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Navarra, Španělsko
- Research Site
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San Sebastian, Španělsko
- Research Site
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Valencia, Španělsko
- Research Site
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Valencia, Španělsko
- Research Site 2
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Age: at least 20 years of age
- Cytologically or histologically confirmed adenocarcinoma of locally advanced or metastatic NSCLC which is not amenable to curative surgery or radiotherapy
- Radiologically confirmed disease progression after at least one line of treatment with an EGFR-TKI
- At least one documented EGFR mutation which is known to be related with susceptibility to EGFR-TKIs (including G719X, exon 19 deletion, L858R, and L861Q)
- World Health Organization (WHO) performance score of 0 to 1 with life expectancy of at least 3 months
- Centrally confirmed T790M mutation positive tumor status from a tumor sample taken after confirmation of disease progression on the most recent anticancer treatment regimen
- At least one lesion (excluding the brain), not previously irradiated that can be accurately measured per RECIST version 1.1
- Adequate hematological and biological function
- Females of child-bearing potential must agree to use adequate contraception and for 3 months after the last dose of study drug
- Male patients should be documented to be sterile or agree to use barrier contraception
- Recovery to ≤ Grade 1 or baseline of any toxicities, except for stable sensory neuropathy ≤ Grade 2 and alopecia
Exclusion Criteria:
- Known history of hypersensitivity to active or inactive excipients of HM61713 or drugs with a similar chemical structure of HM61713
- Previous treatment with anticancer therapies, EGFR-TKI, HM61713, or other drugs that target T790M-positive mutant EGFR with sparing of wild-type, investigational agent(s) within 28 days prior to the first administration of study drug, radiotherapy
- Any non-study related significant surgical procedures within the past 28 days prior to the first administration of study drug
- Spinal cord compression, leptomeningeal carcinomatosis or active symptomatic brain metastases
- History of any other malignancy
- Clinically significant uncontrolled condition(s)
- Active or chronic pancreatitis
- Anyone with cardiac abnormalities or history
- Presence or history of ILD, drug-induced ILD, or presence of radiation pneumonitis
- Pregnant or breast feeding
- In the opinion of the investigator, the patient is an unsuitable candidate to receive HM61713
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
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Experimentální: HM61713
HM61713 800 mg (2 x 400 mg tablets) once daily (QD)
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800 mg QD continuously in 21-day cycles until disease progression determined by investigator assessment per RECIST version 1.1, and as long as, in the investigator"s opinion, they are benefiting from study treatment and they do not meet any of treatment discontinuation criteria.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Objective response rate (ORR)
Časové okno: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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To assess the anti-tumor efficacy of HM61713 as measured by objective response rate (ORR).
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At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Disease control rate (DCR), defined as the proportion of patients with a documented CR, PR, and SD during the treatment cycles according to the RECIST version 1.1
Časové okno: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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To assess clinical efficacy of HM61713 regarding disease control rate (DCR).
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At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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Duration of overall tumor response (DR), defined as the interval between the date of the first observation of tumor response (CR or PR) and the date of disease progression or death
Časové okno: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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To assess clinical efficacy of HM61713 regarding Duration of overall tumor response (DR).
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At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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Progression-free survival (PFS), defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first
Časové okno: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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To assess clinical efficacy of HM61713 regarding Progression-free survival (PFS).
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At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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Overall survival (OS), defined as the time from first administration of study drug until death from any cause
Časové okno: From first dose to end of study or date of death from any cause whichever came first, assessed up to 48 months
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To assess clinical efficacy of HM61713 regarding Overall survival (OS).
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From first dose to end of study or date of death from any cause whichever came first, assessed up to 48 months
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Time to progression (TTP), defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1
Časové okno: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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To assess clinical efficacy of HM61713 regarding Time to progression (TTP).
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At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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Tumor shrinkage calculated as absolute change and percentage change from baseline in sum of tumor size at each assessment using RECIST tumor response
Časové okno: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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To assess clinical efficacy of HM61713 regarding tumor shrinkage.
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At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
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Peak concentration (Cmax) of HM61713
Časové okno: Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22)
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To determine the pharmacokinetic (PK) profile of HM61713.
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Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22)
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Trough plasma concentration (Ctrough) of HM61713
Časové okno: Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22)
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To determine the pharmacokinetic (PK) profile of HM61713.
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Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22)
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Area under the plasma concentration time curve over the 24-hour dosing interval (AUC) of HM61713
Časové okno: Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22)
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To determine the pharmacokinetic (PK) profile of HM61713.
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Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22)
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Patient reported outcomes (PROs)
Časové okno: At baseline and every 6 weeks from time of discontinuation, assessed up to 24 months
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To assess patient reported outcomes (PROs) of health-related quality of life (HRQoL), disease/treatment-related symptoms of lung cancer, and general health status.
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At baseline and every 6 weeks from time of discontinuation, assessed up to 24 months
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ECG/QTc (absolute values and change from baseline)
Časové okno: Adverse events will be collected from baseline until 28 days after the last dose
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To evaluate the effect of HM61713 on the QT interval.
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Adverse events will be collected from baseline until 28 days after the last dose
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Incidence of reported AEs and abnormal laboratory tests (AEs will be assessed using the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4).
Časové okno: Adverse events will be collected from baseline until 28 days after the last dose
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To assess the safety and tolerability of HM61713.
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Adverse events will be collected from baseline until 28 days after the last dose
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QTc interval as assessed by digital ECG with central reading. The QT interval will be rate-corrected using 3 methods: QTcF, QTcB and QTcS.
Časové okno: Adverse events will be collected from baseline until 28 days after the last dose
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To assess the safety and tolerability of HM61713.
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Adverse events will be collected from baseline until 28 days after the last dose
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Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Keunchil Park, M.D., Ph.D, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
- Vrchní vyšetřovatel: Pasi A. Jänne, M.D., Ph.D, Dana-Farber Cancer Institute, Boston, MA, USA
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- HM-EMSI-202
- 2015-001435-21 (Číslo EudraCT)
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