Back to resultsA Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1
Primary Purpose
Advanced or Metastatic Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TAS-114
S-1
Sponsored by
About this trial
This is an interventional treatment trial for Advanced or Metastatic Non-small Cell Lung Cancer focused on measuring NSCLC, phase 2 study, TAS-114, S-1
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years old (≥ 20 years old in Japan);
- Histologically diagnosed or cytologically proven advanced or metastatic NSCLC patients, either Stage IIIB/Stage IV disease (according to Version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or recurrent disease following radiation therapy or surgical resection;
- Patients who had received at least 2 prior therapies for advanced or metastatic disease condition, including platinum doublet and pemetrexed, docetaxel, or immunotherapy, and were refractory to or unable to tolerate their last prior therapy
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009);
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- Predicted life expectancy of at least 3 months;
- Able to take medications orally;
- Adequate organ function
- Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females must agree to use effective birth control during the study (prior to the first dose and for 6 months after the last dose) if conception is possible during this interval.
- Willing and able to comply with required scheduled visits and study procedures.
Exclusion Criteria:
Treatment with any of the following within the specified time frame prior to the study drug administration:
- Major surgery within prior 4 weeks and minor surgery within 7 days;
- Radiotherapy for extended field within prior 4 weeks or limited field within prior 2 weeks;
- Any anticancer therapy or investigational agent within prior 3 weeks.
- A serious illness or medical condition
Concomitant treatment with the following drugs that may interact with S-1:
Sorivudine, brivudine, uracil, eniluracil, folinate/folinic acid, Cimetidine, dipyridamole, and nitroimidazoles, including metronidazole and misonidazoleMethotrexate, Clozapine,Allopurinol,Phenytoin,Flucytosine, a fluorinated pyrimidine antifungal agent,Coumarin-derivative anticoagulant
- Known hypersensitivity to S-1 or its metabolites (eg, 5-FU);
- Previous use of TAS-114, S-1, and 5-FU drugs;
- A pregnant or lactating female or possibly pregnant women, or men or women wishing to have children during the study period;
- A judgment of the investigator that the patient is inappropriate for study participation.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
TAS-114 + S-1
S-1 (Monotherapy)
Arm Description
Participants received 400 milligrams (mg) of TAS-114 tablets orally twice daily (BID) along with 30 milligrams per meter square (mg/m^2) of S-1 capsule BID for 2 weeks (Day 1 to 14), followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 51 weeks).
Participants received 30 mg/m^2 of S-1 capsules BID for 2 weeks (Day 1 to 14) followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 38 weeks).
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS) Based on Central Independent Review
Progression-free survival was defined as the time (in months) from the day of randomization to the start of radiologic disease progression or death (any cause), whichever occurred first. Response assessments were made based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). As per RECIST 1.1 criteria, progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). (Note: the appearance of one or more new lesions was also considered progressions). Participants who did not have disease progression or died were censored at the last known time that the participant was progression free.
Secondary Outcome Measures
Overall Survival (OS)
OS was defined as the time from the first dose of the study treatment to death from any cause. Participants who were alive at the end of study were censored at the last date the participant was known to be alive. OS was estimated from Kaplan-Meier method.
Overall Response Rate (ORR) Based on Central Independent Review
ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and non-target lesions and normalization of tumor marker level. Any pathological and non-pathological lymph nodes must have reduction in short axis to less than (<) 10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters.
Disease Control Rate (DCR) Based on Central Independent Review
DCR was defined as the percentage of participants with objective evidence CR, PR, or stable disease (SD). Based on the central review of tumor assessments per RECIST, version 1.1. CR was defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameters during study.
Duration of Response (DR) Based on Central Independent Review
DR was derived for participants with objective evidence of PR or CR. DR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. Participants who were alive and progression-free as of the analysis cut-off date were censored at their last evaluable tumor response assessment before initiation of any new anticancer treatment.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened during the TEAE period which was defined as the period from the time of first dose of study treatment until 30 days after last dose of study treatment. AEs included both serious and non- serious adverse events.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02855125
Brief Title
A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1
Official Title
A Randomized, Open-Label, Multi-Center, International Phase 2 Study of TAS-114 in Combination With S-1 in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
August 29, 2016 (Actual)
Primary Completion Date
September 30, 2017 (Actual)
Study Completion Date
November 30, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taiho Oncology, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, open-label, Phase 2 study of TAS-114 administered in combination with S-1, to investigate the efficacy, safety and tolerability of the TAS-114/S-1 regimen in patients with advanced or metastatic NSCLC.
The study will be conducted internationally in 2 regions: Asian [Japan] and Western [Europe and US]. Patients will be randomized into TAS-114/S-1 arm versus S-1 control arm in a 1:1 ratio.
Detailed Description
Randomization will take place once the consented patient has completed all the necessary baseline procedures and is deemed eligible for study entry. Treatment assignment will be done centrally using a dynamic allocation method (biased coin) via an interactive voice/web response system (IXRS) stratified by:
Geographical region (Region 1: Asian [Japan]; Region 2: Western [Europe and US])
Histological subtypes (nonsquamous cell carcinoma [including mixed] and squamous cell carcinoma)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced or Metastatic Non-small Cell Lung Cancer
Keywords
NSCLC, phase 2 study, TAS-114, S-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
128 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TAS-114 + S-1
Arm Type
Active Comparator
Arm Description
Participants received 400 milligrams (mg) of TAS-114 tablets orally twice daily (BID) along with 30 milligrams per meter square (mg/m^2) of S-1 capsule BID for 2 weeks (Day 1 to 14), followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 51 weeks).
Arm Title
S-1 (Monotherapy)
Arm Type
Active Comparator
Arm Description
Participants received 30 mg/m^2 of S-1 capsules BID for 2 weeks (Day 1 to 14) followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 38 weeks).
Intervention Type
Drug
Intervention Name(s)
TAS-114
Intervention Description
TAS-114 was a modulator of 5-fluorouracil (5-FU).
Intervention Type
Drug
Intervention Name(s)
S-1
Intervention Description
S-1 was designed to provide oral delivery of 5-FU and to reduce the rate of degradation of 5-FU in vivo.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) Based on Central Independent Review
Description
Progression-free survival was defined as the time (in months) from the day of randomization to the start of radiologic disease progression or death (any cause), whichever occurred first. Response assessments were made based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). As per RECIST 1.1 criteria, progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). (Note: the appearance of one or more new lesions was also considered progressions). Participants who did not have disease progression or died were censored at the last known time that the participant was progression free.
Time Frame
From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the time from the first dose of the study treatment to death from any cause. Participants who were alive at the end of study were censored at the last date the participant was known to be alive. OS was estimated from Kaplan-Meier method.
Time Frame
From date of randomization until death (approximately up to 15 months)
Title
Overall Response Rate (ORR) Based on Central Independent Review
Description
ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and non-target lesions and normalization of tumor marker level. Any pathological and non-pathological lymph nodes must have reduction in short axis to less than (<) 10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters.
Time Frame
From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)
Title
Disease Control Rate (DCR) Based on Central Independent Review
Description
DCR was defined as the percentage of participants with objective evidence CR, PR, or stable disease (SD). Based on the central review of tumor assessments per RECIST, version 1.1. CR was defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameters during study.
Time Frame
From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)
Title
Duration of Response (DR) Based on Central Independent Review
Description
DR was derived for participants with objective evidence of PR or CR. DR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. Participants who were alive and progression-free as of the analysis cut-off date were censored at their last evaluable tumor response assessment before initiation of any new anticancer treatment.
Time Frame
From date of first response to the date of first documentation of progression or death (approximately up to 13 months)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
An adverse event (AE) was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened during the TEAE period which was defined as the period from the time of first dose of study treatment until 30 days after last dose of study treatment. AEs included both serious and non- serious adverse events.
Time Frame
From first dose of study drug up to 30 days after the last dose of study drug (approximately up to 13 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years old (≥ 20 years old in Japan);
Histologically diagnosed or cytologically proven advanced or metastatic NSCLC patients, either Stage IIIB/Stage IV disease (according to Version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or recurrent disease following radiation therapy or surgical resection;
Patients who had received at least 2 prior therapies for advanced or metastatic disease condition, including platinum doublet and pemetrexed, docetaxel, or immunotherapy, and were refractory to or unable to tolerate their last prior therapy
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009);
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
Predicted life expectancy of at least 3 months;
Able to take medications orally;
Adequate organ function
Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females must agree to use effective birth control during the study (prior to the first dose and for 6 months after the last dose) if conception is possible during this interval.
Willing and able to comply with required scheduled visits and study procedures.
Exclusion Criteria:
Treatment with any of the following within the specified time frame prior to the study drug administration:
Major surgery within prior 4 weeks and minor surgery within 7 days;
Radiotherapy for extended field within prior 4 weeks or limited field within prior 2 weeks;
Any anticancer therapy or investigational agent within prior 3 weeks.
A serious illness or medical condition
Concomitant treatment with the following drugs that may interact with S-1:
Sorivudine, brivudine, uracil, eniluracil, folinate/folinic acid, Cimetidine, dipyridamole, and nitroimidazoles, including metronidazole and misonidazoleMethotrexate, Clozapine,Allopurinol,Phenytoin,Flucytosine, a fluorinated pyrimidine antifungal agent,Coumarin-derivative anticoagulant
Known hypersensitivity to S-1 or its metabolites (eg, 5-FU);
Previous use of TAS-114, S-1, and 5-FU drugs;
A pregnant or lactating female or possibly pregnant women, or men or women wishing to have children during the study period;
A judgment of the investigator that the patient is inappropriate for study participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Taiho Central
Organizational Affiliation
Taiho Oncology, Inc. USA
Official's Role
Study Director
Facility Information:
City
Loma Linda
State/Province
California
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Caen
Country
France
City
Lille
Country
France
City
Marseille
Country
France
City
Paris
Country
France
City
Pierre-Bénite
Country
France
City
Villejuif
Country
France
City
Catania
Country
Italy
City
Milano
Country
Italy
City
Palermo
Country
Italy
City
Ravenna
Country
Italy
City
Kashiwa
State/Province
Chiba
Country
Japan
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
City
Adachi
State/Province
Saitama
ZIP/Postal Code
362-0806
Country
Japan
City
Chuo-Ku
State/Province
Tokyo
Country
Japan
City
Koto-Ku
State/Province
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
City
Sunto-Gun
State/Province
Tokyo
Country
Japan
City
Wakayama
ZIP/Postal Code
641-8509
Country
Japan
City
Katowice
Country
Poland
City
Lodz
Country
Poland
City
Lublin
Country
Poland
City
Warszawa
Country
Poland
City
Badalona
Country
Spain
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
32246224
Citation
Yamamoto N, Hayashi H, Planchard D, Moran T, Gregorc V, Dowell J, Sakai H, Yoh K, Nishio M, Cortot AB, Benhadji KA, Soni N, Huang J, Makris L, Cedres S. A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer. Invest New Drugs. 2020 Oct;38(5):1588-1597. doi: 10.1007/s10637-020-00930-5. Epub 2020 Apr 3.
Results Reference
derived
Learn more about this trial
A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1
We'll reach out to this number within 24 hrs