Trial Outcomes & Findings for Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies (NCT NCT01607957)

Last Updated: 2024-09-19

Results Overview

Overall survival was defined as the time from the date of randomization to the date of death for participants. If a participant discontinued study medication for reasons other than radiologic disease progression, the participant was followed for tumor response until radiologic disease progression or initiation of new anticancer therapy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

800 participants

Primary outcome timeframe

Every 8 weeks, up to 12 months after the last participant was randomized or until the target number of events (deaths) was met, whichever was later. (Overall survival data was collected till 24 Jan 2014 which was date of observation of the 571st death)

Results posted on

2024-09-19

Participant Flow

This was a multicenter study conducted in 101 study centers in 13 countries including the United States, Japan, Spain, Italy, Germany, Belgium, France, Australia, United Kingdom, Austria, Ireland, Sweden, and Czech Republic.

Total 1002 participants provided consent, out of which 800 participants were randomized in 2:1 ratio in TAS-102 and placebo treatment groups respectively.

Participant milestones

Participant milestones
Measure	TAS-102 Participants received TAS-102 orally with a starting dose of 35 milligram per meter square per dose (mg/m\^2/dose) twice daily (BID) based on body surface area (BSA) along with best supportive care (BSC). The first dose of TAS-102 was administered in the morning of Day 1 of each cycle and the last dose was administered in the evening of Day 5, followed by rest on Day 6 and 7. The treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle = 28 days). Participants received study medication until any of the discontinuation criteria were met.	Placebo Participants orally received TAS-102 matching placebo BID dose along with BSC with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5, followed by rest on Day 6 and 7. The treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle). Participants received study medication until any of the discontinuation criteria.
Overall Study STARTED	534	266
Overall Study Treated	533	265
Overall Study COMPLETED	162	51
Overall Study NOT COMPLETED	372	215

Reasons for withdrawal

Reasons for withdrawal
Measure	TAS-102 Participants received TAS-102 orally with a starting dose of 35 milligram per meter square per dose (mg/m\^2/dose) twice daily (BID) based on body surface area (BSA) along with best supportive care (BSC). The first dose of TAS-102 was administered in the morning of Day 1 of each cycle and the last dose was administered in the evening of Day 5, followed by rest on Day 6 and 7. The treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle = 28 days). Participants received study medication until any of the discontinuation criteria were met.	Placebo Participants orally received TAS-102 matching placebo BID dose along with BSC with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5, followed by rest on Day 6 and 7. The treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle). Participants received study medication until any of the discontinuation criteria.
Overall Study Not treated	1	1
Overall Study Death	367	211
Overall Study Lost to Follow-up	3	3
Overall Study Participant refusal	1	0

Baseline Characteristics

Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAS-102 n=534 Participants Participants received TAS-102 orally with a starting dose of 35 mg/m\^2/dose BID based on BSA along with BSC. The first dose of TAS-102 was administered in the morning of Day 1 of each cycle and the last dose was administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle = 28 days). Participants received study medication until any of the discontinuation criteria were met.	Placebo n=266 Participants Participants orally received TAS-102 matching placebo BID dose along with BSC with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle). Participants received study medication until any of the discontinuation criteria.	Total n=800 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	300 Participants n=5 Participants	148 Participants n=7 Participants	448 Participants n=5 Participants
Age, Categorical >=65 years	234 Participants n=5 Participants	118 Participants n=7 Participants	352 Participants n=5 Participants
Age, Continuous	61.5 years STANDARD_DEVIATION 10.21 • n=5 Participants	61.5 years STANDARD_DEVIATION 10.51 • n=7 Participants	61.5 years STANDARD_DEVIATION 10.30 • n=5 Participants
Sex: Female, Male Female	208 Participants n=5 Participants	101 Participants n=7 Participants	309 Participants n=5 Participants
Sex: Female, Male Male	326 Participants n=5 Participants	165 Participants n=7 Participants	491 Participants n=5 Participants

PRIMARY outcome

Timeframe: Every 8 weeks, up to 12 months after the last participant was randomized or until the target number of events (deaths) was met, whichever was later. (Overall survival data was collected till 24 Jan 2014 which was date of observation of the 571st death)

Population: Analysis was performed in ITT population. For participants who were alive as of the overall survival cutoff date, their survival was censored on the cutoff date post consent.

Outcome measures

Outcome measures
Measure	TAS-102 n=534 Participants Participants received TAS-102 orally with a starting dose of 35 mg/m\^2/dose BID based on BSA along with BSC. The first dose of TAS-102 was administered in the morning of Day 1 of each cycle and the last dose was administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle = 28 days). Participants received study medication until any of the discontinuation criteria were met.	Placebo n=266 Participants Participants orally received TAS-102 matching placebo BID dose along with BSC with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle). Participants received study medication until any of the discontinuation criteria.
Overall Survival	7.1 months Interval 6.5 to 7.8	5.3 months Interval 4.6 to 6.0

SECONDARY outcome

Timeframe: Every 8 weeks, up to 12 months after the last participant was randomized or until the date of the investigator-assessed radiological disease progression or death due to any cause,whichever was later. (Progression free survival cutoff: 31 Jan 2014)

Population: Analysis was performed in ITT population.

Tumor assessments were performed throughout the study based on RECIST, 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. For participants who were alive with no radiological disease progression as of the analysis cut-off date, their survival was censored at the date of the last tumor assessment. Participants who received non-study cancer treatment before disease progression, or participants with clinical but not radiologic evidence of progression, were censored at the date of the last radiologic evaluable tumor assessment before the non-study cancer treatment was initiated.

Outcome measures

Outcome measures
Measure	TAS-102 n=534 Participants Participants received TAS-102 orally with a starting dose of 35 mg/m\^2/dose BID based on BSA along with BSC. The first dose of TAS-102 was administered in the morning of Day 1 of each cycle and the last dose was administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle = 28 days). Participants received study medication until any of the discontinuation criteria were met.	Placebo n=266 Participants Participants orally received TAS-102 matching placebo BID dose along with BSC with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle). Participants received study medication until any of the discontinuation criteria.
Progression-free Survival	2.0 months Interval 1.9 to 2.1	1.7 months Interval 1.7 to 1.8

SECONDARY outcome

Timeframe: From the time of signing the informed consent form until the period of participant follow up (30 days following after the administration of last dose of study medication or until initiation of new antitumor therapy, whichever was earlier

Population: Safety analysis was performed on as treated (AT) population including all participants who took part of any dose of the study medication.

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.

Outcome measures

Outcome measures
Measure	TAS-102 n=533 Participants Participants received TAS-102 orally with a starting dose of 35 mg/m\^2/dose BID based on BSA along with BSC. The first dose of TAS-102 was administered in the morning of Day 1 of each cycle and the last dose was administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle = 28 days). Participants received study medication until any of the discontinuation criteria were met.	Placebo n=265 Participants Participants orally received TAS-102 matching placebo BID dose along with BSC with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5, followed by rest on Day 6 and 7, treatment was repeated for next week starting from Day 8 to Day 12, followed by a 16-day rest starting from Day 13 to Day 28 (1 treatment cycle). Participants received study medication until any of the discontinuation criteria.
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any adverse event (AE)	98.3 percentage of participants	93.2 percentage of participants
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any treatment-related ≥Grade 3 AE	49.0 percentage of participants	9.8 percentage of participants
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any AE resulting in discontinuation	10.3 percentage of participants	13.6 percentage of participants
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any AE with outcome of death	3.2 percentage of participants	11.3 percentage of participants
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any treatment-related AE	85.7 percentage of participants	54.7 percentage of participants
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any ≥Grade 3 AE	69.4 percentage of participants	51.7 percentage of participants
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths Any serious AE (SAE)	29.6 percentage of participants	33.6 percentage of participants

Adverse Events

TAS-102

Serious events: 158 serious events

Other events: 506 other events

Deaths: 17 deaths

Placebo

Serious events: 89 serious events

Other events: 227 other events

Deaths: 30 deaths

Serious adverse events

Other adverse events

Additional Information

Taiho

Taiho Oncology, Inc.

Phone: +1 844-878-2446

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Taiho agreements vary with individual investigators, but do not prohibit any from publishing. Taiho is provided time to review material discussing trial results (generally 30 to 120 days with possible extension), and can remove undisclosed confidential, proprietary and intellectual property rights-related information. Authors have final control and approval of publication content of final study results. The investigator agrees not to publish any results before the first multicenter publication.
Publication restrictions are in place

Restriction type: OTHER