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出境医 / 临床实验 / Bioequivalence Study of Trifluridine and Tipiracil Tablets in Colorectal Cancer Patients

Bioequivalence Study of Trifluridine and Tipiracil Tablets in Colorectal Cancer Patients

Study Description
Brief Summary:
Trifluridine and Tipiracil Tablets is a nucleoside anti-metabolic and anti-cancer compound developed by Taiho (Dapeng) Co., Ltd., Japan, for the treatment of advanced colorectal cancer that inoperable resection, and progressed or relapsed after standard treatment. This study mainly evaluates bioequivalence, safety and tolerance of Trifluridine and Tipiracil Tablets in colorectal cancer patients.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: Trifluridine and Tipiracil Tablets Drug: TAS-102 Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Single-Dose, Randomized, Open-Label, Two-Way Crossover Study to Evaluate the Bioequivalence of Trifluridine and Tipiracil Tablets in Colorectal Cancer Patients Under Fasting or Postprandial Conditions
Actual Study Start Date : May 22, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: Trifluridine and Tipiracil Tablets Drug: Trifluridine and Tipiracil Tablets
Trifluridine and Tipiracil Tablets given 20mg orally once under fasting or postprandial conditions per cycle

Active Comparator: TAS-102 Drug: TAS-102
TAS-102 given 20mg orally once under fasting or postprandial conditions per cycle

Outcome Measures
Primary Outcome Measures :
  1. AUC(0-infinity) [ Time Frame: 3 days ]
    The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.

  2. AUC(0-t) [ Time Frame: 3 days ]
    The AUC(0-t) is area under the serum concentration-time curve from time zero to t.

  3. Bioequivalence based on Peak Plasma Concentration (Cmax) [ Time Frame: 3 days ]
    The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile


Secondary Outcome Measures :
  1. Adverse Event [ Time Frame: Up to 4 weeks ]
    Security Index


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. 18-70 years old, life expectancy ≥ 3 months.
  2. Histologically confirmed colon or rectal adenocarcinoma.
  3. Has not received anti-tumor therapy before 4 weeks of first dose or Traditional Chinese Medicine anti-tumor therapy before 2 weeks of first dose.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  5. Has ability to take oral medication.
  6. The main organs function are normally, the following criteria are met:

    1. Hemoglobin (HB) ≥ 100 g / L;
    2. Absolute neutrophil count (ANC) ≥1.5×109/L;
    3. Platelets (PLT) ≥ 80 × 109 / L;
    4. Total serum bilirubin (TBIL) ≤ 1.5 × ULN;
    5. Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 × ULN (when the liver is invaded,AST ≤ 5×ULN);
    6. Serum creatinine ≤ 132.6 μmol / L.
  7. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ;No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
  8. Understood and signed an informed consent form.

Exclusion Criteria:

  1. Has serious diseases , including but not limited to:

    1. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. Exceptions include carcinoma in situ of cervix, non-melanoma skin cancer and superficial bladder tumor;
    2. Has brain metastases;
    3. Has active infection (such as infection caused body temperature ≥ 38 ° C);
    4. Has pleural effusion, pericardial effusion, or ascites requiring recurrent drainage before 4 weeks of first dose;
    5. Has intestinal obstruction, pulmonary fibrosis, renal failure, liver failure or symptomatic cerebrovascular disease;
    6. Has uncontrolled diabetes (fasting blood glucose (FBG) > 10mmol/L);
    7. Has myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) grade III or IV symptomatic congestive heart failure within 12 months prior to first dose;
    8. Has gastrointestinal bleeding;
    9. Has HIV infection, or active hepatitis B or C;
    10. Has a history of organ transplants or autoimmune disease required immunosuppressive therapy;
    11. Has increased risk associated with participating in the study or taking the study drug, or mental disorders may interfere with the results of the study.
  2. Has received any of the following treatments before the first dose:

    1. Has received partial or total gastrectomy;
    2. Has surgery (such as laparotomy, thoracotomy, and laparoscopic resection of the viscera and/or unhealed wounds) within 4 weeks;
    3. Has any study drug within 4 weeks.
  3. Prior therapy with TAS-102.
  4. Has adverse events caused by previous therapy except alopecia that did not recover to ≤ grade 2.
  5. Pregnant or lactating woman.
  6. Subjects who, in the opinion of the investigators, should not participate in the study.
Contacts and Locations

Contacts
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Contact: Helong Zhang, Doctor 135 1912 8910 cntdccc@126.com

Locations
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China, Shanxi
Tangdu Hospital,Fourth Military Medical University Recruiting
Xi'an, Shanxi, China, 710038
Contact: Helong Zhang, Doctor    135 1912 8910    cntdccc@126.com   
Sponsors and Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Tracking Information
First Submitted Date  ICMJE May 31, 2019
First Posted Date  ICMJE June 5, 2019
Last Update Posted Date June 5, 2019
Actual Study Start Date  ICMJE May 22, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • AUC(0-infinity) [ Time Frame: 3 days ]
    The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.
  • AUC(0-t) [ Time Frame: 3 days ]
    The AUC(0-t) is area under the serum concentration-time curve from time zero to t.
  • Bioequivalence based on Peak Plasma Concentration (Cmax) [ Time Frame: 3 days ]
    The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
Adverse Event [ Time Frame: Up to 4 weeks ]
Security Index
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 Bioequivalence Study of Trifluridine and Tipiracil Tablets in Colorectal Cancer Patients
Official Title  ICMJE Single-Dose, Randomized, Open-Label, Two-Way Crossover Study to Evaluate the Bioequivalence of Trifluridine and Tipiracil Tablets in Colorectal Cancer Patients Under Fasting or Postprandial Conditions
Brief Summary Trifluridine and Tipiracil Tablets is a nucleoside anti-metabolic and anti-cancer compound developed by Taiho (Dapeng) Co., Ltd., Japan, for the treatment of advanced colorectal cancer that inoperable resection, and progressed or relapsed after standard treatment. This study mainly evaluates bioequivalence, safety and tolerance of Trifluridine and Tipiracil Tablets in colorectal cancer patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: Trifluridine and Tipiracil Tablets
    Trifluridine and Tipiracil Tablets given 20mg orally once under fasting or postprandial conditions per cycle
  • Drug: TAS-102
    TAS-102 given 20mg orally once under fasting or postprandial conditions per cycle
Study Arms  ICMJE
  • Experimental: Trifluridine and Tipiracil Tablets
    Intervention: Drug: Trifluridine and Tipiracil Tablets
  • Active Comparator: TAS-102
    Intervention: Drug: TAS-102
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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 31, 2019)
64
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 18-70 years old, life expectancy ≥ 3 months.
  2. Histologically confirmed colon or rectal adenocarcinoma.
  3. Has not received anti-tumor therapy before 4 weeks of first dose or Traditional Chinese Medicine anti-tumor therapy before 2 weeks of first dose.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  5. Has ability to take oral medication.
  6. The main organs function are normally, the following criteria are met:

    1. Hemoglobin (HB) ≥ 100 g / L;
    2. Absolute neutrophil count (ANC) ≥1.5×109/L;
    3. Platelets (PLT) ≥ 80 × 109 / L;
    4. Total serum bilirubin (TBIL) ≤ 1.5 × ULN;
    5. Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 × ULN (when the liver is invaded,AST ≤ 5×ULN);
    6. Serum creatinine ≤ 132.6 μmol / L.
  7. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ;No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
  8. Understood and signed an informed consent form.

Exclusion Criteria:

  1. Has serious diseases , including but not limited to:

    1. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. Exceptions include carcinoma in situ of cervix, non-melanoma skin cancer and superficial bladder tumor;
    2. Has brain metastases;
    3. Has active infection (such as infection caused body temperature ≥ 38 ° C);
    4. Has pleural effusion, pericardial effusion, or ascites requiring recurrent drainage before 4 weeks of first dose;
    5. Has intestinal obstruction, pulmonary fibrosis, renal failure, liver failure or symptomatic cerebrovascular disease;
    6. Has uncontrolled diabetes (fasting blood glucose (FBG) > 10mmol/L);
    7. Has myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) grade III or IV symptomatic congestive heart failure within 12 months prior to first dose;
    8. Has gastrointestinal bleeding;
    9. Has HIV infection, or active hepatitis B or C;
    10. Has a history of organ transplants or autoimmune disease required immunosuppressive therapy;
    11. Has increased risk associated with participating in the study or taking the study drug, or mental disorders may interfere with the results of the study.
  2. Has received any of the following treatments before the first dose:

    1. Has received partial or total gastrectomy;
    2. Has surgery (such as laparotomy, thoracotomy, and laparoscopic resection of the viscera and/or unhealed wounds) within 4 weeks;
    3. Has any study drug within 4 weeks.
  3. Prior therapy with TAS-102.
  4. Has adverse events caused by previous therapy except alopecia that did not recover to ≤ grade 2.
  5. Pregnant or lactating woman.
  6. Subjects who, in the opinion of the investigators, should not participate in the study.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03974594
Other Study ID Numbers  ICMJE CTTQ-TAS-102-I-02
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 Not Provided
Responsible Party Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study Sponsor  ICMJE Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Verification Date May 2019

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

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