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Trial record 12 of 37 for:    Recruiting, Not yet recruiting, Available Studies | Receptor tyrosine kinase

Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of ASK120067 in Locally Advanced and Metastatic Non Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03502850
Recruitment Status : Recruiting
First Posted : April 19, 2018
Last Update Posted : April 19, 2018
Sponsor:
Information provided by (Responsible Party):
Jiangsu Aosaikang Pharmaceutical Co., Ltd.

Brief Summary:
ASK120067 Tablets is a Epidermal Growth Factor Receptor (EGFR) mutation selective Tyrosine Kinase Inhibitor which can efficient suppress the EGFR T790M drug-resistant mutation tumor cell in Xenograft mouse model. This study aims at local advanced or metastatic non-small cell lung cancer patients with T790M drug-resistant mutation.

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic NSCLC Drug: ASK120067 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study to Assess the Safety,Tolerability, Pharmacokinetics and Anti-tumour Activity of ASK120067 in Patients With Locally Advanced or Metastatic T790M Mutation-positive Non-Small Cell Lung Cancer Who Have Progressed Following Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
Actual Study Start Date : November 30, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ASK120067
patients take ASK120067 orally once per day at different dose
Drug: ASK120067
patients take Alflutinib orally once per day at 40,80,120,180,240,320,400mg




Primary Outcome Measures :
  1. Objective response rate [ Time Frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years. ]
    Evaluation of objective response rate assessed by RECIST 1.1


Secondary Outcome Measures :
  1. Incidence and Severity of Treatment-Emergent Adverse Events [ Time Frame: Adverse events will be collected from baseline until 28 days after the last dose ]
    Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations and NCI CTCAE v4.03

  2. Progression free survival [ Time Frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years. ]
    Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival

  3. Duration of response [ Time Frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years. ]
    Duration of response assessed by RECIST 1.1

  4. Disease control rate [ Time Frame: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression,date of death or withdrawal from study,whichever came first, assessed up to approximately 2 years. ]
    Evaluation of Disease control rate assessed by RECIST 1.1

  5. Overall survival [ Time Frame: Time from treatment start to the time of death due to any cause or withdrawal from study,whichever came first, assessed up to approximately 2 years. ]
    difined as the time from date of first dose until date of death due to any cause

  6. Maximum Plasma Concentration [Cmax] of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points of Day 1 to figure out Cmax

  7. Peak Plasma Time [tmax] of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolite following single dose at designated time points of Day 1 to figure out tmax

  8. Area under the plasma concentration versus time curve (AUC) of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolite following single dose at designated time points of Day1 to figure out AUC

  9. Terminal rate constant of single dose single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolite following single dose at designated time points of Day 1 to figure out terminal rate constant

  10. Clearance of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolite following single dose at designated time points of Day 1 to figure out clearance

  11. Half life of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolite following single dose at designated time points of Day 1 to figure out half life

  12. Volume of distribution of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of f ASK120067 and 1 metabolite following single dose at designated time points of Day 1 to figure out volume of distribution

  13. Mean resistance time of single dose ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times after the first dose of the study on Day 1, (pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24, 48, 72 ,96,144 hours post dose) ]
    Collect plasma concentrations of ASK120067 and 1 metabolite following single dose at designated time points of Day 1 to figure out mean resistance time

  14. Steady state Cmax of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    Cmax of ASK120067 and 1 metabolite at steady state following multiple doses

  15. Steady state tmax of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    Tmax of ASK120067 and 1 metabolite at steady state following multiple doses

  16. Steady state Cmin (Minimum Plasma Concentration) of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    Cmin of ASK120067 and 1 metabolite at steady state following multiple doses

  17. Steady state AUC of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    AUC of ASK120067 and 1 metabolite at steady state following multiple doses

  18. Steady state clearance of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    Clearance of ASK120067 and 1 metabolite at steady state following multiple doses

  19. Accumulation ratio of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    Accumulation ratio of ASK120067 and 1 metabolite following multiple doses

  20. Time dependency of multiple doses ASK120067 [ Time Frame: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 8, 10,12,15,18,22. Cycle 1 D28- pre-dose, 1, 2, 3, 4, 5,6, 8, 10, 24 hours post dose) ]
    Time dependency of ASK120067 and 1 metabolite following multiple doses



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of either gender, aged from 18 years older to 70.
  • Histologically or cytologically confirmed metastatic, or unresectable locally advanced, recurrent NSCLC
  • Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation)
  • Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib or Afatinib, or Icotinib (Third EGFR TKI are not included). In addition other lines of therapy may have been given
  • Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy)
  • At least one measurable disease by CT or PET-CT or MRI, according to RECIST Version 1.1
  • ECOG performance status of 0 to 2.
  • Life expectancy of at least 12 weeks
  • Females should not be in lactation period and must have a negative pregnancy test prior to start of dosing; During the whole treatment,all patients should be in the entire 3 months during and after the treatment, repeated barrier precautions
  • Signed consent on an Independent Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation

Exclusion Criteria:

  • Any cytotoxic chemotherapy from a previous treatment regimen or clinical study within 28 days,Any Target cancer drug from a previous treatment regimen or clinical study within 8 days, or less than approximately 5x half-life of the first dose of study treatment;
  • The third EGFR-TKI from a previous treatment regimen or clinical study (ie, AZD9291, CO-1686, HM61713, ASP8273, EGF816, avitinib)
  • Major surgery within 4 weeks of the first dose of study treatment
  • Taking (or cannot stop taking 1 week before the first dose receiving) strong inhibitor of CYP3A4
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy
  • Spinal compression, or brain metastasis exhibiting symptoms but untreated (except those exhibit no symptom with stable condition and do not apply corticosteroids for 4 weeks before the trail initiating)
  • Any evidence showing severe or inadequate controlled systemic disease. For example patients with inadequate controlled hypertension or active hemorrhagic tendency considered not suitable for the trail or would affect the compliance towards the protocol
  • Active infection such as HBV (HBV-DNA≥1000cps/ml), with HCV, with HIV et al (except for HBV carrier those the researcher considered meet the criterion).
  • Any condition affecting the drug taking, or significantly affecting the absorption or the pharmacokinetic parameters, include any kind of uncontrollable nausea or vomit, chronic gastroenteropathy, disability in swallowing, and history of gastrointestinal resection or surgery
  • Any condition meet the following cardiac standard: Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 ECG. All kinds of abnormal in cardiac rhythm, conduction and resting ECG profile with clinical significance, for example complete left bundle branch block, 2 or 3 grade of conduction block and a PR interval>250 msec. Any possible factors increasing the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
  • Any history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonia require steroid therapy or active interstitial lung disease with clinical evidence during recruiting
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Absolute neutrophil count < 1.5 x 109/L. Platelet count < 100 x 109/L. Haemoglobin < 90 g/L. Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN.
  • History of hypersensitivity to active or inactive excipients of ASK120067 or drugs with a similar chemical structure or class to ASK120067
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03502850


Contacts
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Contact: Tingting Song 025-85100150 songtingting@ask-pharm.com
Contact: Liang Ni 025-85100634 niliang@ask-pharm.com

Locations
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China, Beijing
Chinese Academy of Medical Sciences Not yet recruiting
Beijing, Beijing, China, 100021
Contact: Yuankai Shi         
Principal Investigator: Yuankai Shi         
Beijing Chest Hospital,Capital Medical University Recruiting
Beijing, Beijing, China, 101149
Contact: Baolan Li         
Principal Investigator: Baolan Li         
China, Tianjin
Tianjin Medical University Cancer Insititute & Hospital Not yet recruiting
Tianjin, Tianjin, China, 300060
Contact: Kai Li         
Principal Investigator: Kai Li         
Sponsors and Collaborators
Jiangsu Aosaikang Pharmaceutical Co., Ltd.

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Responsible Party: Jiangsu Aosaikang Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT03502850     History of Changes
Other Study ID Numbers: ASK-LC-120067-Ⅰ/Ⅱ
First Posted: April 19, 2018    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases