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
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Darlinghurst, Australien
- Research Site
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Fitzroy, Australien
- Research Site
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Frankston, Australien
- Research Site
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Kogarah, Australien
- Research Site
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St Albans, Australien
- Research Site
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Woolloongabba, Australien
- Research Site
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Toronto, Canada
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Cebu, Filippinerne
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Kalakhang Maynila
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Makati, Kalakhang Maynila, Filippinerne
- Research Site
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Manila
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Pasig, Manila, Filippinerne
- Research Site
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Metro Manila
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Manila, Metro Manila, Filippinerne
- Research Site 2
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Manila, Metro Manila, Filippinerne
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California
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Beverly Hills, California, Forenede Stater
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Burbank, California, Forenede Stater
- Research Site
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Los Angeles, California, Forenede Stater
- Research Site
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Los Angeles, California, Forenede Stater
- Research Site 2
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Montebello, California, Forenede Stater
- Research Site
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Orange, California, Forenede Stater
- Research Site
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San Diego, California, Forenede Stater
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Florida
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Boca Raton, Florida, Forenede Stater
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Hawaii
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Honolulu, Hawaii, Forenede Stater
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Illinois
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Evanston, Illinois, Forenede Stater
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Maryland
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Bethesda, Maryland, Forenede Stater
- Research Site
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Massachusetts
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Boston, Massachusetts, Forenede Stater
- Research Site
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New Hampshire
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Lebanon, New Hampshire, Forenede Stater
- Research Site
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North Carolina
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Charlotte, North Carolina, Forenede Stater
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Washington
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Washington, Washington, Forenede Stater
- Research Site
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Bergamo, Italien
- Research Site
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Bologna, Italien
- Research Site
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Catania, Italien
- Research Site
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Milano, Italien
- Research Site
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Rome, Italien
- Research Site
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Cheongju-si, Korea, Republikken
- Research Site
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Goyang-si, Korea, Republikken
- Research Site
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Hwasun, Korea, Republikken
- Research Site
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Incheon, Korea, Republikken
- Research Site
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Seongnam-si, Korea, Republikken
- Research Site 2
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Seongnam-si, Korea, Republikken
- Research Site
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Seoul, Korea, Republikken
- Research Site
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Seoul, Korea, Republikken
- Research Site 2
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Seoul, Korea, Republikken
- Research Site 3
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Seoul, Korea, Republikken
- Research Site 4
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Seoul, Korea, Republikken
- Research Site 5
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Seoul, Korea, Republikken
- Research Site 6
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Seoul, Korea, Republikken
- Research Site 7
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Seoul, Korea, Republikken
- Research Site 8
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Kuala Lumpur, Malaysia
- Research Site
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Kuantan, Malaysia
- Research Site
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Kuching, Malaysia
- Research Site
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Penang
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George Town, Penang, Malaysia
- Research Site
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Barcelona, Spanien
- Research Site
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Barcelona, Spanien
- Research Site 2
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Barcelona, Spanien
- Research Site 3
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Barcelona, Spanien
- Research Site 4
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La Coruna, Spanien
- Research Site
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Madrid, Spanien
- Research Site
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Madrid, Spanien
- Research Site 2
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Navarra, Spanien
- Research Site
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San Sebastian, Spanien
- Research Site
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Valencia, Spanien
- Research Site
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Valencia, Spanien
- Research Site 2
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Kaohsiung, Taiwan
- Research Site
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Taichung, Taiwan
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Tainan, Taiwan
- Research Site
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Tainan, Taiwan
- Research Site 2
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Taipei, Taiwan
- Research Site
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Taipei, Taiwan
- Research Site 2
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Berlin, Tyskland
- Research Site
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Homburg, Tyskland
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Leipzig, Tyskland
- Research Site
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München, Tyskland
- Research Site
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Ulm, Tyskland
- Research Site
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
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Eksperimentel: 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.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Objective response rate (ORR)
Tidsramme: 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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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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).
Tidsramme: 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.
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Ledende efterforsker: Keunchil Park, M.D., Ph.D, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
- Ledende efterforsker: Pasi A. Jänne, M.D., Ph.D, Dana-Farber Cancer Institute, Boston, MA, USA
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- HM-EMSI-202
- 2015-001435-21 (EudraCT nummer)
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