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Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia (TERRA)

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ClinicalTrials.gov Identifier: NCT01955837
Recruitment Status : Completed
First Posted : October 8, 2013
Results First Posted : November 17, 2020
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Taiho Pharmaceutical Co., Ltd.

Brief Summary:
To compare the effects of TAS-102 with placebo in patients with metastatic colorectal cancer refractory or intolerable to standard chemotherapies.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: TAS-102 Drug: Placebo Phase 3

Detailed Description:
This is a multinational, double-blind, two-arm, parallel, randomized Phase 3 comparison study evaluating the efficacy and safety of TAS-102 versus placebo in patients with refractory metastatic colorectal cancer. Patients will be randomly assigned (2:1) to TAS-102 (experimental arm) or placebo (control arm).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 406 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Phase III Study of TAS-102 Versus Placebo in Asian Patients With Metastatic Colorectal Cancer Refractory or Intolerable to Standard Chemotherapies
Study Start Date : September 2013
Actual Primary Completion Date : February 16, 2016
Actual Study Completion Date : June 30, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAS-102 Drug: TAS-102
TAS-102 (35 mg/m2/dose) orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.

Placebo Comparator: Placebo Drug: Placebo
Placebo orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria is met.




Primary Outcome Measures :
  1. Overall Survival(OS) [ Time Frame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later. ]
    The primary endpoint was Overall Survival (OS), which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met. ]
    Tumor assessments were performed throughout the study period and analyzed using Response Evaluation Criteria in Solid Tumors criteria (Version 1.1, 2009). Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment.

  2. Time to Treatment Failure (TTF) [ Time Frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months. ]
    Time to treatment failure was defined as the time (in months) from the date of randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause. Censoring for TTF was also applied for those patients who were given non-study cancer treatment, with censoring at the time when the patient began the non-study cancer treatment.

  3. Overall Response Rate (ORR; Complete Response [CR] or Partial Response [PR] Using RECIST Criteria) [ Time Frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months. ]
    The assessment of ORR was based on Investigator review of the images according to RECIST Version 1.1. Overall response rate was defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). At the analysis stage, the best overall response was assigned for each patient as the best response recorded from all responses recorded after study randomization. If applicable, responses recorded after disease progression or initiation of non-study cancer treatment was excluded. A patient's best response assignment of stable disease (SD) needed to be maintained for at least 6 weeks after study randomization. If a patient didn't meet this condition, best response was assigned "Not evaluable".

  4. Disease Control Rate (DCR; CR, PR, or Stable Disease) [ Time Frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months. ]
    The assessment of DCR paralleled that of ORR, with DCR defined as the proportion of patients with objective evidence of CR, PR, or SD.

  5. Duration of Response [ Time Frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months. ]
    Duration of response was derived for those patients with objective evidence of PR or CR. Duration of response was defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause. Patients alive and progression free as of the analysis cut-off date were censored at their last evaluable tumor response assessment prior to initiation of any non-study cancer treatment.

  6. Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments(Adverse Events) [ Time Frame: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months. ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AEs were events between administration of study drug and up to 30 Days that were absent before treatment or that worsened relative to pre-treatment state. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability /incapacity; congenital anomaly. The AEs were graded for severity using National Cancer Institute Common Terminology Criteria for AEs.

  7. Safety and Tolerability Evaluation Will Focus on Adverse Events and Laboratory Assessments(Laboratory Assessments) [ Time Frame: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months. ]
    All laboratory values that were out of the normal range were to be evaluated for their clinical significance before exposing the patient to the next dose of study medication. Any laboratory abnormality that was clinically significant, e.g., results in delay of study medication dosing, study discontinuation, required treatment due to abnormal values, or was considered by the Investigator to be medical important, were to be reported as an AE, unless it was considered part of clinical manifestations to a clinical diagnosis that has already been reported as an AE.

  8. Overall Survival(OS)(Wild Type KRAS) [ Time Frame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later. ]

    The primary end point was OS, which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

    The OS indicated above as secondary outcome was analyzed by wild type KRAS.


  9. Overall Survival(OS)(Mutant Type KRAS) [ Time Frame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later. ]

    The primary end point was OS, which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

    The OS indicated above as secondary outcome was analyzed by mutant type KRAS.


  10. Progression-free Survival (PFS) (Wild Type KRAS) [ Time Frame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met. ]
    Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment. The PFS indicated above as secondary outcome was analyzed by wild type KRAS.

  11. Progression-free Survival (PFS) (Mutant Type KRAS) [ Time Frame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met. ]
    Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment. The PFS indicated above as secondary outcome was analyzed by mutant type KRAS.



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

Inclusion Criteria:

  • Has provided written informed consent
  • Has adenocarcinoma of the colon or rectum
  • Has failed at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Is able to take medication orally
  • Has adequate organ function (bone marrow, kidney and liver)
  • Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

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): NCT01955837


Locations
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China
Peking University Cancer Hospital
Beijing, China, 100142
Fudan University Shanghai Cancer Center
Shanghai, China, 200032
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Thailand
Chulalongkorn University & The King Chulalongkorn Memorial Hospital
Bangkok, Thailand, 10330
Sponsors and Collaborators
Taiho Pharmaceutical Co., Ltd.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Taiho Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT01955837    
Other Study ID Numbers: 10040090
First Posted: October 8, 2013    Key Record Dates
Results First Posted: November 17, 2020
Last Update Posted: November 17, 2020
Last Verified: October 2020
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases