Diffuse Gastric and Esophagogastric Junction Cancer S-1 Trial (DIGEST)

August 30, 2024 updated by: Taiho Oncology, Inc.

An Open-Label, Multicenter, Randomized, Phase 3 Study of S-1 and Cisplatin Compared With 5-FU and Cisplatin in Patients With Metastatic Diffuse Gastric Cancer Previously Untreated With Chemotherapy

The purpose of this study is to evaluate the safety and efficacy of S-1 and Cisplatin compared to 5-FU and Cisplatin in treatment of patients with metastatic diffuse gastric and gastro-esophageal junction cancer previously untreated with chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, international, Phase 3 study evaluating the efficacy and safety of the S-1/cisplatin regimen versus the 5-FU/cisplatin regimen in chemotherapy-naïve patients with metastatic diffuse gastric carcinoma including carcinoma of the gastro-esophageal junction. Patients will be randomly assigned to S-1/cisplatin (experimental regimen, Arm A) or 5-FU/cisplatin (control regimen, Arm B).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
361

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Autonoma de Buenos Aires, Argentina, 1264
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000KZE
  • Belgium
      • Bruxelles, Belgium, 1200
      • Edegem, Belgium, 2650
      • Gent, Belgium, 9000
  • Brazil
      • Belo Horizonte, Brazil, 31110-580
      • Fortaleza, Brazil, 60160-230
      • Ijuí, Brazil, 98700-000
      • Porto Alegre, Brazil, 90050-170
    • BA
      • Salvador, BA, Brazil, 41820-021
    • RS
      • Porto Alegre, RS, Brazil, 90610-000
    • SP
      • Barretos, SP, Brazil, 14784-400
      • Ribeirão Preto, SP, Brazil, 14015-130
      • São Paulo, SP, Brazil, 01246-000
      • São Paulo, SP, Brazil, 01406-100
  • Bulgaria
      • Pleven, Bulgaria, 5800
      • Vratsa, Bulgaria, 3000
  • Croatia
      • Osijek, Croatia, 31000
      • Zagreb, Croatia, 10000
  • Estonia
      • Tallinn, Estonia, 11312
      • Tallinn, Estonia, 13419
  • Germany
      • Essen, Germany, 45147
  • Hungary
      • Budapest, Hungary, 1122
      • Budapest, Hungary, 1032
      • Győor, Hungary, 9024
      • Nyíregyháza, Hungary, 4400
      • Pécs, Hungary, 7624
      • Szeged, Hungary, 6720
      • Székesfehérvár, Hungary, 8000
  • Israel
      • Tel Aviv, Israel, 64239
  • Italy
      • Ancona, Italy, 60020
      • Candiolo, Italy, 10060
      • Milano, Italy, 20141
      • Modena, Italy, 41100
      • Potenza, Italy, 85100
      • Reggio Emilia, Italy, 42100
      • Rimini, Italy, 47900
  • Mexico
      • Chihuahua, Mexico, 31000
      • Mexico City, Mexico, 14080
      • Oaxaca, Mexico, 68000
  • Poland
      • Szczecin, Poland, 71-730
      • Warszawa, Poland, 02-781
  • Portugal
      • Aveiro, Portugal, 3814-501
      • Coimbra, Portugal, 3000-226
      • Lisboa, Portugal, 1649-035
      • Porto, Portugal, 4200-072
  • Romania
      • Baia Mare, Romania, 430031
      • Cluj-Napoca, Romania, 400015
      • Craiova, Romania, 200385
      • Iasi, Romania, 700106
  • Russian Federation
      • Barnaul, Russian Federation, 656049
      • Krasnodar, Russian Federation, 350040
      • Moscow, Russian Federation, 115478
      • Pyatigorsk, Russian Federation, 357502
      • Saint Petersburg, Russian Federation, 197022
      • Saint Petersburg, Russian Federation, 197758
      • Saint-Petersburg, Russian Federation, 194214
  • South Africa
    • Gauteng
      • Groenkloof Pretoria, Gauteng, South Africa, 0181
      • Pretoria, Gauteng, South Africa, 0002
    • KZN
      • Durban, KZN, South Africa, 4091
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7500
  • Spain
      • Barcelona, Spain, 08036
      • Barcelona, Spain, 08035
      • Barcelona, Spain, 08907
      • Madrid, Spain, 28046
      • Madrid, Spain, 28034
      • Madrid, Spain, 28007
      • Madrid, Spain, 28033
      • Madrid, Spain, 28050
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
  • Ukraine
      • Cherkassy, Ukraine, 18009
      • Chernivtsiy, Ukraine, 58013
      • Dnepropetrovsk, Ukraine, 49102
      • Donetsk, Ukraine, 83092
      • Kharkiv, Ukraine, 61070
      • Kyiv, Ukraine, 3115
      • Lutsk, Ukraine, 43018
      • Lviv, Ukraine, 79031
      • Sumy, Ukraine, 40005
      • Uzhgorod, Ukraine, 88000
      • Zaporizzhya, Ukraine, 69040
  • United Kingdom
      • London, United Kingdom, W12 0NN
    • Wales
      • Rhyl, Wales, United Kingdom, LL18 5UJ
  • United States
    • Louisiana
      • Alexandria, Louisiana, United States, 71301
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
    • Texas
      • Dallas, Texas, United States, 75390
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has given written Informed Consent.
  • Histologically confirmed, unresectable, metastatic diffuse gastric cancer including carcinoma of the gastro-esophageal junction.
  • No prior chemotherapy for gastric cancer except adjuvant and/or neo-adjuvant chemotherapy more than 12 months ago.
  • Life expectancy of at least 3 months.
  • Able to take medications orally.
  • Eastern Cooperative Oncology Group performance status 0 to 1.
  • Adequate organ function (bone marrow, kidney and liver).

Exclusion Criteria:

  • Certain type(s) of non-measurable lesion(s), if the only one(s).
  • Certain serious illness or medical condition(s).
  • Lost greater than or equal to 10% of body weight in the 3 months proceeding signing the Informed Consent Form.
  • Treatment with drugs interacting with S-1, 5-FU, or cisplatin.
  • Pregnant or lactating female.
  • Known hypersensitivity to fluoropyrimidines or cisplatin.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: S-1+Cisplatin
Participants received S-1 25 milligrams per meter square (mg/m^2) orally twice daily (BID) every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m^2 as a 1- to 3-hour intravenous (IV) infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until progression of disease (PD), adverse event (AE), withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Drug: S-1 (Tegafur+Gimeracil+Oteracil) /cisplatin (investigational arm)
25 mg/m² body surface area (BSA) orally 2 times daily from Days 1 through 21 followed by a 7 day rest period, plus cisplatin 75 mg/m2 BSA on Day 1 each 28 day cycle Number of Cycles: until progression or unacceptable toxicity develops. Treatment with cisplatin is limited to a maximum of 8 cycles.
Other Names:
  • TS-1, Tegafur+Gimeracil+Oteracil
Active Comparator: 5FU+Cisplatin
Participants received 5-Fluorouracil (5-FU) 800 mg/m^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Drug: Fluorouracil/cisplatin (control arm)

5-FU: 800 mg/m2 BSA/24 hours by continuous intravenous infusion (CIV) from Days 1 through 5 plus cisplatin 80 mg/m2 BSA on Day 1 each 21 day cycle.

Number of Cycles: until progression or unacceptable toxicity develops. Treatment with cisplatin is limited to a maximum of 8 cycles.

Other Names:
  • TS-1, Tegafur+Gimeracil+Oteracil

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From the date of randomization until disease progression or death, cut-off date: 15 August 2014 (approximately 40 months)
OS was defined as the time from randomization to the date of death for the ITT population. Participants who did not die were censored at the date last known to be alive. Analysis was performed by using Kaplan-Meier method.
From the date of randomization until disease progression or death, cut-off date: 15 August 2014 (approximately 40 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: From date of randomization until disease progression or death, cut-off date: 07 March 2014 (approximately 34.7 months)
PFS was defined as the time from date of randomization until date of radiological disease progression or death due to any cause. Disease Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where any of the 3 criteria have been met: 1) at least 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study, including the baseline sum, 2) Progression in no-target lesion(s), 3) appearance of new lesion(s) Participants who were alive with no PD were censored at the date of the last tumor assessment. Participants who received new anticancer therapy before disease progression were censored at the date of the last evaluable tumor assessment before new anticancer therapy was initiated. Analysis was performed by using Kaplan-Meier method.
From date of randomization until disease progression or death, cut-off date: 07 March 2014 (approximately 34.7 months)
Time to Treatment Failure (TTF)
Time Frame: From date of randomization until disease progression, cut-off date: 07 March 2014 (approximately 34.7 months)
TTF was defined as the time from date of randomization until date of PD (clinical or radiologic), or permanent discontinuation of study treatment (S-1 or 5-FU), or death due to any cause. Participates who were still on study treatment at the time of the analysis were censored at the last date the participants was known to be on treatment.
From date of randomization until disease progression, cut-off date: 07 March 2014 (approximately 34.7 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE)
Time Frame: From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)
AE was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily had to have a causal relationship with the use of the study medication. 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 or became serious during on-treatment period (from first dose of study medication up to 30 days of last study medication [maximum duration: 35.7 months]).
From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)
Number of Participants With TEAEs With Severity Greater Than or Equal to (>=) Grade 3
Time Frame: From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)
An AE was any untoward medical condition that occurred in a participants while participating in a clinical study and does not necessarily had to have a causal relationship with the use of the study medication. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (from first dose of study medication up to 30 days of last study medication [maximum duration: 35.7 months]).
From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)
Overall Response Rate (ORR): Percentage of Participants With Overall Response
Time Frame: From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)
ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) based on the Investigator review of the images and application of Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to less than (<) 10 millimeter (mm). PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference.
From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)
Duration of Response (DR)
Time Frame: From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)
Duration of response was defined as the time (in months) from date of first confirmed response (CR or PR) to date of first progressive disease (PD) or death. Per the RECIST criteria, definitions were as follows: CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to <10 mm. Analysis was performed by using Kaplan-Meier method.
From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)
Time to Tumor Response (TTR)
Time Frame: From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)
TTR was defined as the time (in months) from the date of randomization to the date of first observation of response (PR or CR) (whichever status was recorded first). TTR was assessed based on investigator assessment utilizing RECIST 1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to <10 mm. PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference. Analysis was performed by using Kaplan-Meier method.
From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Taiho Oncology, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Taiho Central, Taiho Oncology, Inc. USA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 14, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 26, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TPU-S1303

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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