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出境医 / 临床实验 / Study of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC

Study of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC

Study Description
Brief Summary:
This is a phase I, open label, dose escalation study to evaluate tolerability, safety , pharmacokinetics and efficacy in patients with KRAS mutant NSCLC by using HL-085 and Docetaxel.

Condition or disease Intervention/treatment Phase
Nsclc Drug: HL-085 Drug: Docetaxel Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: If no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I , Single Arm, Dose Escalation Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC
Estimated Study Start Date : August 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: dose escalation of HL-085 plus Docetaxel

HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV).

f no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.

 Drug: HL-085
HL-085 ( Capsule) is one MEK inhibitor.

Drug: Docetaxel
Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.
Outcome Measures
Primary Outcome Measures :
  1. Number of Adverse Events (AEs) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 will be counted.

  2. Maximum tolerated dose (MTD) [ Time Frame: DLTs within the first cycle of therapy (up to 35 days) ]
    The dose level immediately below the dose level at which more than 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT)


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    ORR is the proportion of patients with a best overall response of complete response (CR) or partial response (PR), as assessed per response evaluation criteria in solid tumors (RECIST) v1.1.

  2. Peak Plasma Concentration (Cmax) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    Cmax is the maximum plasma concentration of HL-085 or metabolite(s).

  3. Area under the plasma concentration verus time curve(AUC) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    AUC of HL-085 or metabolites(s) after repeated dosing


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. KRAS mutation NSCLC.
  2. One measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
  3. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment.
  4. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
  5. ECOG performance status of 0-1.
  6. Life expectancy ≥ 3 months.
  7. Ability to take the medicine orally.
  8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Hypersensitivity to study drug ingredients or their analogues.
  2. Prior therapy with MEK-inhibitor.
  3. Receiving any other anti-cancer therapy at the same time .
  4. Active central nervous system (CNS) lesion.
  5. Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment.
  6. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome；
  7. Uncontrolled concomitant diseases or infectious diseases.
  8. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
  9. History of HIV,HCV,HBV infection.
  10. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
  11. Serum HCG test is positive.
  12. Other conditions that increase the risk of study and influence the result.
Contacts and Locations

Contacts
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Contact: Jin Ma, Bachelor 0086 213810268600 maj@kechowpharma.com

Locations
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China
Cancer Hospital Chinese Academy of Medical Science
Beijing, China, 100021
Contact: Yuankai Shi         
Sponsors and Collaborators
Shanghai Kechow Pharma, Inc.
Investigators
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Study Director: Hongqi Tian, PhD Shanghai Kechow Pharma.
Tracking Information
First Submitted Date  ICMJE June 12, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date December 21, 2020
Estimated Study Start Date  ICMJE August 2021
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2019)
  • Number of Adverse Events (AEs) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 will be counted.
  • Maximum tolerated dose (MTD) [ Time Frame: DLTs within the first cycle of therapy (up to 35 days) ]
    The dose level immediately below the dose level at which more than 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2019)
  • Overall response rate (ORR) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    ORR is the proportion of patients with a best overall response of complete response (CR) or partial response (PR), as assessed per response evaluation criteria in solid tumors (RECIST) v1.1.
  • Peak Plasma Concentration (Cmax) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    Cmax is the maximum plasma concentration of HL-085 or metabolite(s).
  • Area under the plasma concentration verus time curve(AUC) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    AUC of HL-085 or metabolites(s) after repeated dosing
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC
Official Title  ICMJE A Phase I , Single Arm, Dose Escalation Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC
Brief Summary This is a phase I, open label, dose escalation study to evaluate tolerability, safety , pharmacokinetics and efficacy in patients with KRAS mutant NSCLC by using HL-085 and Docetaxel.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
If no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Nsclc
Intervention  ICMJE
  • Drug: HL-085
    HL-085 ( Capsule) is one MEK inhibitor.
  • Drug: Docetaxel
    Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.
Study Arms  ICMJE Experimental: dose escalation of HL-085 plus Docetaxel

HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV).

f no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.

Interventions:
  • Drug: HL-085
  • Drug: Docetaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2019) 		27
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. KRAS mutation NSCLC.
  2. One measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
  3. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment.
  4. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
  5. ECOG performance status of 0-1.
  6. Life expectancy ≥ 3 months.
  7. Ability to take the medicine orally.
  8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Hypersensitivity to study drug ingredients or their analogues.
  2. Prior therapy with MEK-inhibitor.
  3. Receiving any other anti-cancer therapy at the same time .
  4. Active central nervous system (CNS) lesion.
  5. Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment.
  6. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome；
  7. Uncontrolled concomitant diseases or infectious diseases.
  8. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
  9. History of HIV,HCV,HBV infection.
  10. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
  11. Serum HCG test is positive.
  12. Other conditions that increase the risk of study and influence the result.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jin Ma, Bachelor 0086 213810268600 maj@kechowpharma.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03990077
Other Study ID Numbers  ICMJE HL-085-103
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Shanghai Kechow Pharma, Inc.
Study Sponsor  ICMJE Shanghai Kechow Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hongqi Tian, PhD Shanghai Kechow Pharma.
PRS Account Shanghai Kechow Pharma, Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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