Study of TAS-102 or Placebo Plus BSC in Patients With Metastatic Gastric Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to compare the effects of TAS-102 and best supportive care (BSC) with Placebo (an inactive drug) and best supportive care on metastatic gastric cancer.

Detailed Description
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This is a multinational, double-blind, two-arm, parallel, randomized, Phase 3 study evaluating the efficacy and safety of TAS-102 plus BSC versus placebo plus BSC in participants with metastatic gastric cancer who have previously received at least 2 prior regimens for advanced disease. Eligible participants will be centrally randomized (2:1) to TAS-102 + BSC (experimental arm) or placebo + BSC (control arm).

Official Title
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Randomized, Double-blind, Phase 3 Study Evaluating TAS-102 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Gastric Cancer Refractory to Standard Treatments

Conditions
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Refractory Metastatic Gastric Cancer

Intervention / Treatment
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* Drug: TAS-102
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically confirmed non-resectable, metastatic gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction. Has previously received at least 2 prior regimens for advanced disease and were refractory to or unable to tolerate their last prior therapy. Has measureable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Is able to take medications orally (ie, no feeding tube). Has an Eastern Cooperative Oncology Group performance status of 0 or 1. Has adequate organ function as defined by protocol defined labs. 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. Exclusion Criteria: Has certain serious illnesses or medical conditions Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent within the specified time frames prior to study drug administration. Has previously received TAS-102. Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events Grade 2 attributed to any prior therapies. Is a pregnant or lactating female.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-102+BSC<br>Participants received 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice daily (BID) for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until a discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | Drug: TAS-102<br>* 35 mg/m2/dose of TAS-102 orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle.<br>|
| Experimental: Placebo+BSC<br>Participants received 35 mg/m^2 of matching placebo for TAS-102 tablets orally BID for 5 days per week (i.e., from Days 1 to 5 and Days 8 to 12) for 2 weeks followed by 14 days rest in each 28-day cycle along with BSC until discontinuation criterion (participant withdrawal, disease progression, irreversible treatment-related Grade 4 non-hematologic event, physician's decision, pregnancy or death) was met. | Drug: Placebo<br>* 35 mg/m2/dose of placebo orally, twice daily on days 1-5 and days 8-12 of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death were censored at last follow-up or cut-off date, whichever comes first. OS was estimated by Kaplan-Meier method. | From the date of randomization to the data cut-off date (maximum duration: up to approximately 46 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined as the time from randomization until the date of first occurrence of investigator-assessed radiological disease progression or death due to any cause, whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for target lesions were defined as target lesions with at least 20 % relative increase in the sum of diameters with reference to the smallest sum on study, including the baseline sum and this sum demonstrated an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions or Unequivocal progression of existing non-target lesions. All alive participants with no disease progression as of the analysis cut-off date were censored at the last tumor assessment. PFS was estimated by Kaplan-Meier method. | From the date of randomization to the cut-off date (maximum duration: up to approximately 46 months) | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) | 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 medication was considered an adverse event (AE). 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/TESAEs were defined as events that started on or after treatment or started before treatment and worsened after the start of treatment through 30 days after the last dose of study treatment. | From the first dose of study treatment until 30 days after the last dose of study treatment (maximum duration: up to approximately 46 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Metastatic Gastric Cancer