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出境医 / 临床实验 / Personalized Mini-PDX for Metastatic CRPC

Personalized Mini-PDX for Metastatic CRPC

Study Description
Brief Summary:
The investigators intend to use the Second-generation sequencing(NGS)and MiniPDX drug sensitivity models to guide the treatment decision-making for patients who were resistant to abiraterone, enzalutamide or other new second-generation anti-androgenic drugs. In order to develop precise personalized treatment plans for patients and extent their lifetimes.

Condition or disease Intervention/treatment Phase
Prostate Cancer Other: MiniPDX Group Not Applicable

Detailed Description:
Most patients with metastatic prostate cancer are effective in endocrine therapy at the beginning, but after a median survival of 12 to 18 months, almost all patients develop castration-resistant prostate cancer (CRPC). Since the pathogenesis of CRPC is still unknown, the clinical lack of precise treatment for the cause is a difficult and hot topic in current research and treatment. Mini patient derived xenograft (MiniPDX) is a drug sensitivity test model established by transplanting primary human tumor cells into immunodeficient mice by special methods. This efficient drug sensitivity test can provide sensitivities of single drug or drug combination in order to screen out the optimal individualized regimens for each patient. The investigators intend to use the Second-generation sequencing(NGS)and MiniPDX drug sensitivity models to guide the treatment decision-making for patients who were resistant with abiraterone, enzalutamide or other new second-generation anti-androgenic drugs. This project is to develop precise personalized treatment plans for patients and extent their lifetimes.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-center, Open, Real World and Prospective Trial of Personalized Mini Patient-Derived Xenograft (MiniPDX ) Modeling in Adult Patients With Metastatic Castration Resistant Prostate Cancer
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : January 27, 2020
Estimated Study Completion Date : January 27, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: MiniPDX Group
Patients medication plan based on MiniPDX drug sensitivity test.
Other: MiniPDX Group
Mini patient derived xenograft (MiniPDX) is a drug sensitivity test model established by transplanting primary human tumor cells into immunodeficient mice by special methods. This test can provide sensitivities of single drug or drug combination within 7 days to screen out the optimal individualized regimens for each patient.

Outcome Measures
Primary Outcome Measures :
  1. ORR [ Time Frame: 12 months ]
    The ratio of number of participants with evidence of a confirmed complete response (CR) or partial response (PR) to all participants is objective response rate (ORR) by using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 to evaluate.


Secondary Outcome Measures :
  1. PFS [ Time Frame: 12 months ]
    Progression-free survival (PFS) is defined as the time from the date of the first administration of patients medication plan based on MiniPDX drug sensitivity test to the date of the first documentation of disease progression or death due to any cause, whichever comes first, censored at the last date at which the participant was determined to be progression-free.

  2. OS [ Time Frame: 12 months ]
    Overall survival is defined as time from initiation to death of any cause.

  3. ADR [ Time Frame: Up to 30 days of last study treatment. ]
    Adverse Drug Reaction:Adverse events determined according to CTCAE (version 4.03) and attribution to study treatment.

  4. Clinical Consistency [ Time Frame: Up to 2 months of last study treatment. ]
    Overall clinical consistency(accuracy) as assessed by evaluating Response Evaluation Criteria In Solid Tumors (RECIST) criteria in patient tumor and correlating to tumor regression in Mini-PDX model for same drug treatment.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient can provide detailed clinical baseline information including: name, age, gender, pathology, past treatment, etc.;
  2. Male, age ≥ 18 years old;
  3. ECOG score 0~2 points;
  4. Patient must be able to provide tissue samples for the drug sensitive test;
  5. No treatment history with PI3K inhibitors, AKT inhibitors or mTOR inhibitors;
  6. Estimated lifetime is ≥ 3 months;
  7. Histological or cytologically determined prostate adenocarcinoma, excluding neuroendocrine differentiation, signet ring cell carcinoma and small cell carcinoma;
  8. Patient is at a castration level and the testosterone level is lower than <50 ng/dL or 1.7 nmol/L;
  9. Received abiraterone or enzalutamide and other new second-generation anti-androgenic drugs and have disease progression. Disease progression is defined by PCWG3 :The progression of disease in PCWG3 is defined as satisfying one of the following: according to the increase in PSA levels, there must be three consecutive increases in PSA at least one week apart, and the minimum value is greater than or equal to 5.0 ng/ml; disease progression as assessed by RECIST 1.1, considering PSA levels or not; PCWG3 defines bone disease progression, which is bone scan found 2 or more new lesions;
  10. Evidence of distant metastatic disease (such as bone scans and CT/MRI results), imaging data that can be used to assess the condition before and after treatment, or imaging experience provided by three imaging hospitals with experience in three hospitals. Test reports and oncology indicators include PSA values;
  11. The patient can tolerate the primary physician to perform the puncture operation, after receiving the informed consent from the patient and the family members;
  12. The follow-up period must be at least greater than 2 months;
  13. Be able to follow the research and follow-up procedures to provide real and effective information;
  14. The patient or his legal guardian understands the test procedure and content and voluntarily signs the printed informed consent form.

Exclusion Criteria:

  1. Cognitive ability and psychological abnormalities
  2. ECOG score 3-4 points or blood biochemical examination indicates that the patient is not suitable for continuing chemotherapy or chemotherapy has been postponed
  3. Can not provide enough tumor puncture tissue, not enough tumor cells for subsequent experiments;
  4. Patient who is unwilling to receive follow-up treatment after the Mini PDX model drug sensitivity test;
  5. The investigator believes that the subject may not be able to complete the study or may not be able to comply with the requirements of this study (for administrative reasons or other reasons).
Contacts and Locations

Contacts
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Contact: Haitao Wang, Ph.D +86-022-88326385 peterrock2000@126.com

Locations
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China, Tianjin
Tianjin Medical University Second Hospital Recruiting
Tianjin, Tianjin, China, 300211
Contact: Haitao Wang         
Sponsors and Collaborators
Tianjin Medical University Second Hospital
Investigators
Layout table for investigator information
Principal Investigator: Haitao Wang Tianjin Medical University Second Hospital
Tracking Information
First Submitted Date  ICMJE December 6, 2018
First Posted Date  ICMJE December 26, 2018
Last Update Posted Date November 26, 2019
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date January 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2018)
ORR [ Time Frame: 12 months ]
The ratio of number of participants with evidence of a confirmed complete response (CR) or partial response (PR) to all participants is objective response rate (ORR) by using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 to evaluate.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 24, 2018)
  • PFS [ Time Frame: 12 months ]
    Progression-free survival (PFS) is defined as the time from the date of the first administration of patients medication plan based on MiniPDX drug sensitivity test to the date of the first documentation of disease progression or death due to any cause, whichever comes first, censored at the last date at which the participant was determined to be progression-free.
  • OS [ Time Frame: 12 months ]
    Overall survival is defined as time from initiation to death of any cause.
  • ADR [ Time Frame: Up to 30 days of last study treatment. ]
    Adverse Drug Reaction:Adverse events determined according to CTCAE (version 4.03) and attribution to study treatment.
  • Clinical Consistency [ Time Frame: Up to 2 months of last study treatment. ]
    Overall clinical consistency(accuracy) as assessed by evaluating Response Evaluation Criteria In Solid Tumors (RECIST) criteria in patient tumor and correlating to tumor regression in Mini-PDX model for same drug treatment.
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 Personalized Mini-PDX for Metastatic CRPC
Official Title  ICMJE A Single-center, Open, Real World and Prospective Trial of Personalized Mini Patient-Derived Xenograft (MiniPDX ) Modeling in Adult Patients With Metastatic Castration Resistant Prostate Cancer
Brief Summary The investigators intend to use the Second-generation sequencing(NGS)and MiniPDX drug sensitivity models to guide the treatment decision-making for patients who were resistant to abiraterone, enzalutamide or other new second-generation anti-androgenic drugs. In order to develop precise personalized treatment plans for patients and extent their lifetimes.
Detailed Description Most patients with metastatic prostate cancer are effective in endocrine therapy at the beginning, but after a median survival of 12 to 18 months, almost all patients develop castration-resistant prostate cancer (CRPC). Since the pathogenesis of CRPC is still unknown, the clinical lack of precise treatment for the cause is a difficult and hot topic in current research and treatment. Mini patient derived xenograft (MiniPDX) is a drug sensitivity test model established by transplanting primary human tumor cells into immunodeficient mice by special methods. This efficient drug sensitivity test can provide sensitivities of single drug or drug combination in order to screen out the optimal individualized regimens for each patient. The investigators intend to use the Second-generation sequencing(NGS)and MiniPDX drug sensitivity models to guide the treatment decision-making for patients who were resistant with abiraterone, enzalutamide or other new second-generation anti-androgenic drugs. This project is to develop precise personalized treatment plans for patients and extent their lifetimes.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE Other: MiniPDX Group
Mini patient derived xenograft (MiniPDX) is a drug sensitivity test model established by transplanting primary human tumor cells into immunodeficient mice by special methods. This test can provide sensitivities of single drug or drug combination within 7 days to screen out the optimal individualized regimens for each patient.
Study Arms  ICMJE Experimental: MiniPDX Group
Patients medication plan based on MiniPDX drug sensitivity test.
Intervention: Other: MiniPDX Group
Publications * Zhang F, Wang W, Long Y, Liu H, Cheng J, Guo L, Li R, Meng C, Yu S, Zhao Q, Lu S, Wang L, Wang H, Wen D. Characterization of drug responses of mini patient-derived xenografts in mice for predicting cancer patient clinical therapeutic response. Cancer Commun (Lond). 2018 Sep 26;38(1):60. doi: 10.1186/s40880-018-0329-5.

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 24, 2018)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 27, 2021
Estimated Primary Completion Date January 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient can provide detailed clinical baseline information including: name, age, gender, pathology, past treatment, etc.;
  2. Male, age ≥ 18 years old;
  3. ECOG score 0~2 points;
  4. Patient must be able to provide tissue samples for the drug sensitive test;
  5. No treatment history with PI3K inhibitors, AKT inhibitors or mTOR inhibitors;
  6. Estimated lifetime is ≥ 3 months;
  7. Histological or cytologically determined prostate adenocarcinoma, excluding neuroendocrine differentiation, signet ring cell carcinoma and small cell carcinoma;
  8. Patient is at a castration level and the testosterone level is lower than <50 ng/dL or 1.7 nmol/L;
  9. Received abiraterone or enzalutamide and other new second-generation anti-androgenic drugs and have disease progression. Disease progression is defined by PCWG3 :The progression of disease in PCWG3 is defined as satisfying one of the following: according to the increase in PSA levels, there must be three consecutive increases in PSA at least one week apart, and the minimum value is greater than or equal to 5.0 ng/ml; disease progression as assessed by RECIST 1.1, considering PSA levels or not; PCWG3 defines bone disease progression, which is bone scan found 2 or more new lesions;
  10. Evidence of distant metastatic disease (such as bone scans and CT/MRI results), imaging data that can be used to assess the condition before and after treatment, or imaging experience provided by three imaging hospitals with experience in three hospitals. Test reports and oncology indicators include PSA values;
  11. The patient can tolerate the primary physician to perform the puncture operation, after receiving the informed consent from the patient and the family members;
  12. The follow-up period must be at least greater than 2 months;
  13. Be able to follow the research and follow-up procedures to provide real and effective information;
  14. The patient or his legal guardian understands the test procedure and content and voluntarily signs the printed informed consent form.

Exclusion Criteria:

  1. Cognitive ability and psychological abnormalities
  2. ECOG score 3-4 points or blood biochemical examination indicates that the patient is not suitable for continuing chemotherapy or chemotherapy has been postponed
  3. Can not provide enough tumor puncture tissue, not enough tumor cells for subsequent experiments;
  4. Patient who is unwilling to receive follow-up treatment after the Mini PDX model drug sensitivity test;
  5. The investigator believes that the subject may not be able to complete the study or may not be able to comply with the requirements of this study (for administrative reasons or other reasons).
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Haitao Wang, Ph.D +86-022-88326385 peterrock2000@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03786848
Other Study ID Numbers  ICMJE MiniPDX-CRPC
Has Data Monitoring Committee No
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: No
Responsible Party Tianjin Medical University Second Hospital
Study Sponsor  ICMJE Tianjin Medical University Second Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Haitao Wang Tianjin Medical University Second Hospital
PRS Account Tianjin Medical University Second Hospital
Verification Date November 2019

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

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