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出境医 / 临床实验 / Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer

Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer

Study Description
Brief Summary:
The majority of endometrial cancer patients with disease spread beyond the uterus will progress within 1 year. Platinum-based chemotherapy was used as the first-line treatment in metastatic or advanced endometrial cancer. There is no standard protocol for the second-line option when tumors persist or recur. In vitro and in vivo studies showed Crizotinib, an approved drug for the treatment of ALK-positive non-small cell lung cancer, demonstrated activities in endometrial cancer with c-MET kinase and Sema domain mutations. As a consequence, a phase 2 clinical trial to investigate the efficacy of Crizotinib in endometrial cancer patients with MET mutation is initiated.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Recurrent Drug: Crizotinib 250 MG Phase 2

Detailed Description:
In this phase 2 study, the target population is patients with recurrent or persistent metastatic endometrial cancer. The mutation status of c-MET gene will be tested and only patients with c-MET mutation will be enrolled. After enrollment, Crizotinib 250 mg bid will be used orally. CT scan or MRI will be used to determine the response. Crizotinib will be continued till disease progression. Primary end is objective response rate. The secondary endpoints include progression-free survival, overall survival and safety profiles.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : December 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Crizotinib arm
Crizotinib 250 mg bid orally
 Drug: Crizotinib 250 MG
bid orally
Other Name: Xalkori 250 MG
Outcome Measures
Primary Outcome Measures :
  1. Change in best overall response rate [ Time Frame: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks ]
    CT scan or MRI will be used to evaluate the response every 2 cycles according to the RECIST 1.1 criteria. The best overall response rate is the proportion of patients in whom a complete response (CR) or partial response (PR) was observed.


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks ]
    CT scan or MRI will be used to evaluate the response according to RECIST 1.1 criteria. Progression-free survival is defined as the time from the time of treatment to disease progression or death from any cause.

  2. Overall survival [ Time Frame: Overall survival will be followed from the start of treatment to death from any cause, up to 104 weeks ]
    Overall survival is defined as defined as the time from the start of treatment to death from any cause.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age no less than 20 years and no more than 75 years, at the time of acquisition of informed consent.
  • Histological confirmed epithelial endometrial cancer
  • Disease recurrent after curative therapy or adjuvant therapy including surgery, chemotherapy, radiotherapy or hormone therapy
  • Metastatic/recurrent/persistent endometrial cancer
  • Tumor tissue with high expression in immunohistochemistry stain (IHC) or somatic c-MET mutation
  • Patients with symptomatic recurrent lesion or Image diagnosis (including ultrasound, Computed Tomography or Magnetic Resonance Imaging) recurrent status
  • ECOG Performance status 0-2
  • At least one distinct tumor, not previous irradiated, measurable lesion according to RECIST (version 1.1)
  • Adequate organ function

Bone marrow:

Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L WBC ≥ 3.0 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 9 g/dL

Hepatic:

Total bilirubin level ≤ 1.0 x UNL AST and ALT ≤ 3.0 x UNL Renal: Creatinine level ≤ 1.5 mg/dL in men, ≤1.4 mg/dL in women; or Estimated CCr ≥ 60 mL/min (CCr is estimated by Cockcroft-Gault formula)

  • Negative pregnancy test for women of childbearing potential only
  • Patient willing to provide blood sample for research purposes
  • Written informed consent

Exclusion Criteria:

  • Presence or history of malignancy disease other than endometrial cancer that has been diagnosed with past five years
  • Other anti-tumor agent such as systemic chemotherapy, hormone therapy or surgery within 2 weeks before the commencement of study treatment or radiotherapy within 4 weeks before the commencement of study
  • Active uncontrolled infection
  • Significant medical diseases, such as unstable angina, acute or recent myocardial infarction (<6 months before enrollment), COPD with frequent exacerbation, uncontrolled hypertension, ore cent CVA (<6 months before enrollment)
  • Poor compliance
  • Pregnant or breastfeeding women, where pregnancy is confirmed by a positive hCG laboratory test.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Keng-Fu Hsu, PhD +886-6-2353535 ext 5222 d5580@mail.ncku.edu.tw

Sponsors and Collaborators
National Cheng-Kung University Hospital
Chi Mei Medical Hospital
Kaohsiung Medical University
Kaohsiung Veterans General Hospital.
Investigators
Layout table for investigator information
Principal Investigator: Keng-Fu Hsu, PhD National Cheng-Kung University Hospital
Tracking Information
First Submitted Date  ICMJE May 24, 2019
First Posted Date  ICMJE July 24, 2019
Last Update Posted Date August 26, 2019
Estimated Study Start Date  ICMJE September 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2019) 		Change in best overall response rate [ Time Frame: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks ]
CT scan or MRI will be used to evaluate the response every 2 cycles according to the RECIST 1.1 criteria. The best overall response rate is the proportion of patients in whom a complete response (CR) or partial response (PR) was observed.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • Progression-free survival [ Time Frame: CT scan or MRI will be done at baseline and at the end of every 2 cycles (each cycle is 28 days) until the date of first documented progression or date of death from any cause, whichever came first, up to 104 weeks ]
    CT scan or MRI will be used to evaluate the response according to RECIST 1.1 criteria. Progression-free survival is defined as the time from the time of treatment to disease progression or death from any cause.
  • Overall survival [ Time Frame: Overall survival will be followed from the start of treatment to death from any cause, up to 104 weeks ]
    Overall survival is defined as defined as the time from the start of treatment to death from any cause.
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 Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer
Official Title  ICMJE Phase II Trial of Crizotinib in c-MET Mutation Metastatic/Recurrent/Persistent Endometrial Cancer
Brief Summary The majority of endometrial cancer patients with disease spread beyond the uterus will progress within 1 year. Platinum-based chemotherapy was used as the first-line treatment in metastatic or advanced endometrial cancer. There is no standard protocol for the second-line option when tumors persist or recur. In vitro and in vivo studies showed Crizotinib, an approved drug for the treatment of ALK-positive non-small cell lung cancer, demonstrated activities in endometrial cancer with c-MET kinase and Sema domain mutations. As a consequence, a phase 2 clinical trial to investigate the efficacy of Crizotinib in endometrial cancer patients with MET mutation is initiated.
Detailed Description In this phase 2 study, the target population is patients with recurrent or persistent metastatic endometrial cancer. The mutation status of c-MET gene will be tested and only patients with c-MET mutation will be enrolled. After enrollment, Crizotinib 250 mg bid will be used orally. CT scan or MRI will be used to determine the response. Crizotinib will be continued till disease progression. Primary end is objective response rate. The secondary endpoints include progression-free survival, overall survival and safety profiles.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Endometrial Cancer Recurrent
Intervention  ICMJE Drug: Crizotinib 250 MG
bid orally
Other Name: Xalkori 250 MG
Study Arms  ICMJE Experimental: Crizotinib arm
Crizotinib 250 mg bid orally
Intervention: Drug: Crizotinib 250 MG
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: July 23, 2019) 		40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age no less than 20 years and no more than 75 years, at the time of acquisition of informed consent.
  • Histological confirmed epithelial endometrial cancer
  • Disease recurrent after curative therapy or adjuvant therapy including surgery, chemotherapy, radiotherapy or hormone therapy
  • Metastatic/recurrent/persistent endometrial cancer
  • Tumor tissue with high expression in immunohistochemistry stain (IHC) or somatic c-MET mutation
  • Patients with symptomatic recurrent lesion or Image diagnosis (including ultrasound, Computed Tomography or Magnetic Resonance Imaging) recurrent status
  • ECOG Performance status 0-2
  • At least one distinct tumor, not previous irradiated, measurable lesion according to RECIST (version 1.1)
  • Adequate organ function

Bone marrow:

Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L WBC ≥ 3.0 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 9 g/dL

Hepatic:

Total bilirubin level ≤ 1.0 x UNL AST and ALT ≤ 3.0 x UNL Renal: Creatinine level ≤ 1.5 mg/dL in men, ≤1.4 mg/dL in women; or Estimated CCr ≥ 60 mL/min (CCr is estimated by Cockcroft-Gault formula)

  • Negative pregnancy test for women of childbearing potential only
  • Patient willing to provide blood sample for research purposes
  • Written informed consent

Exclusion Criteria:

  • Presence or history of malignancy disease other than endometrial cancer that has been diagnosed with past five years
  • Other anti-tumor agent such as systemic chemotherapy, hormone therapy or surgery within 2 weeks before the commencement of study treatment or radiotherapy within 4 weeks before the commencement of study
  • Active uncontrolled infection
  • Significant medical diseases, such as unstable angina, acute or recent myocardial infarction (<6 months before enrollment), COPD with frequent exacerbation, uncontrolled hypertension, ore cent CVA (<6 months before enrollment)
  • Poor compliance
  • Pregnant or breastfeeding women, where pregnancy is confirmed by a positive hCG laboratory test.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Keng-Fu Hsu, PhD +886-6-2353535 ext 5222 d5580@mail.ncku.edu.tw
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04030429
Other Study ID Numbers  ICMJE B-BR-108-016
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
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Cheng-Kung University Hospital
Study Sponsor  ICMJE National Cheng-Kung University Hospital
Collaborators  ICMJE
  • Chi Mei Medical Hospital
  • Kaohsiung Medical University
  • Kaohsiung Veterans General Hospital.
Investigators  ICMJE
Principal Investigator: Keng-Fu Hsu, PhD National Cheng-Kung University Hospital
PRS Account National Cheng-Kung University Hospital
Verification Date June 2019

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

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