CancerPhase 2NCT03519074
Cisplatin Combined with Oral TS-1 in Patients with Advanced Solid Tumors with Different Degrees of Liver Dysfunction
A Phase 2 study testing TS-1 combined with cisplatin in people with Cancer and Liver Dysfunction, run by National University Hospital, Singapore at 2 sites in Singapore.
Trial summary
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Cancer, Liver Dysfunction
- What is being tested?
- TS-1 combined with cisplatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 2 sitesSingapore
- Study dates
- 22 Jul 2016to 20 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must fulfill ALL the following inclusion criteria
- Age 18 years.
- Histologic or cytologic diagnosis of carcinoma, that is either refractory to standard therapy or has no available therapies.
- Measurable disease using the RECIST v1.1 criteria
- ECOG performance 0 or 1.
- Estimated life expectancy of at least 12 weeks.
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- Adequate bone marrow and renal function as follows:
- Bone marrow: Absolute neutrophil count (ANC) 1.5 x 109/L Platelets 100 x 109/L Renal: calculated creatinine clearance >60ml/minute Total bilirubin and AST/ALT as described in Table 1
- Able to swallow pills
- Signed informed consent from patient or legal representative
- Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study.
- Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
Who cannot join
- Patients will be excluded from the study for any of the following reasons:
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Treatment of a small molecule targeted agents ≤ 2 weeks prior to starting study treatment
- Treatment within the last 30 days with any investigational drug.
- Radiotherapy ≤4 weeks prior to starting study treatment or who have not recovered from radiotherapy-related toxicities. Limited field palliative radiotherapy ≤ 2 weeks prior to starting study treatment is allowed
- Major surgery within 28 days of study drug administration.
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- History or presence of serious uncontrolled ventricular arrhythmias
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TS-1 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
- Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- Pregnancy.
- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
Trial locations and contacts
2 sites in 1 country.
Singapore2 sites
National University Hospital
Singapore, Singapore, 119228
Ng Teng Fong General Hospital
Singapore, Singapore, 609606
About this study
Official title: Phase II Trial of Cisplatin Combined with Oral TS-1 in Patients with Advanced Solid Tumors with Different Degrees of Liver Dysfunction
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the United States National Cancer Institute organ dysfunction working group [NCI-ODWG] criteria for hepatic dysfunction.
Read the detailed description
Hepatic impairment is a common co-morbidity in cancer patients, particularly in those with extensive liver metastases. Decreased drug clearance as a result of impaired liver function may lead to increased systemic exposure and possibly greater toxicity. As many chemotherapeutic agents are metabolized by the liver, treatment options tend to be limited in patients with severe hepatic impairment, even in the presence of good performance status and adequate other organ function. Cisplatin is an active chemotherapeutic agent with broad spectrum activity that can safely be administered in severe hepatic impairment. Cisplatin has been combined safely with full dose oral TS-1 with good efficacy in a spectrum of solid tumors in patients with adequate renal and hepatic function.
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the United States National Cancer Institute organ dysfunction working group [NCI-ODWG] criteria for hepatic dysfunction.
- Conditions
- Cancer, Liver Dysfunction
- Being tested
- TS-1 combined with cisplatin
- Medical subject headings
- Neoplasms, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TS-1 combined with cisplatinDrug
Cisplatin 60mg/m2, day 1, every 21 days Oral TS-1 30mg/m2 bd, days 1-14, every 21 days (absolute dose of oral TS-1 will be 40-60mg bd days 1-14, every 21 days, depending on body surface area)
| Study group | Role | What they receive |
|---|---|---|
| TS-1 combined with cisplatin | Experimental | Eligible patients will be stratified by degree of liver dysfunction into 4 cohorts, in accordance to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria Receives: Drug: TS-1 combined with cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy evaluations: Disease status
Efficacy evaluations will be performed using the RECIST v1.1 criteria
Measurable disease:
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of 10mm on CT scan Malignant lymph node: ≥15mm in short axis on CT scan
Non-measurable disease: All other lesions, including small lesions (longest diameter <10mm or pathological lymph nodes with >10 to <15mm short axis) as well as truly non-measurable lesions
Measured: Radiological evaluation of tumor status every 2 cycles of cisplatin and oral TS-1 from baseline until documented disease progression; assessed up to 12 months
Efficacy Evaluation: Timing
The duration of tumor response is measured from the date of enrollment until the first date of documented disease progression or death due to any cause, whichever occurs first.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2018
- Study start22 Jul 2016
- Primary completion1 Sep 2024
- Study completion20 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03519074
- Sponsor's protocol ID
- 2016/00691
- Other IDs
- 2016
- Status last verified
- Sep 2024
- First submitted
- 2 Apr 2018
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schoffski P. The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors. Anticancer Drugs. 2004 Feb;15(2):85-106. doi: 10.1097/00001813-200402000-00001.
PubMed 15075664Yamamoto D, Iwase S, Tsubota Y, Ariyoshi K, Kawaguchi T, Miyaji T, Sueoka N, Yamamoto C, Teramoto S, Odagiri H, Kitamura K, Nagumo Y, Yamaguchi T. Randomized study of orally administered fluorinated pyrimidines (capecitabine versus S-1) in women with metastatic or recurrent breast cancer: Japan Breast Cancer Research Network 05 Trial. Cancer Chemother Pharmacol. 2015 Jun;75(6):1183-9. doi: 10.1007/s00280-015-2738-3. Epub 2015 Apr 11.
PubMed 25862350Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. doi: 10.1016/S1470-2045(15)00411-8. Epub 2015 Nov 27.
PubMed 26617202Gwee YX, Wong ALA, Goh BC, Soo RA, Yong WP, Tan DSP, Chee CE, Lim SE, Ang Y, Huang Y, Chong WQ, Lim J, Chan G, Ngoi N, Ow S, Wong R, Sooi K, Choo J, Lee SC. Prospective evaluation of combination oral S-1 and intravenous cisplatin in cancer patients with severe hepatic dysfunction - a feasibility, safety, and pharmacokinetic study. Front Oncol. 2026 Oct 16;16:1948986. doi: 10.3389/fonc.2026.1948986. eCollection 2026.
PubMed 42964102
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Cisplatin Combined with Oral TS-1 in Patients with Advanced Solid Tumors with Different Degrees of Liver Dysfunction
- ClinicalTrials.gov ID
- NCT03519074
- Acronym / sponsor ID
- 2016/00691
- Conditions
- Cancer, Liver Dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 22 Jul 2016 (actual)
- Primary completion
- 1 Sep 2024 (actual)
- Study completion
- 20 Dec 2025 (estimated)
- First posted
- 8 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the United States National Cancer Institute organ dysfunction working group [NCI-ODWG] criteria for hepatic dysfunction.
Detailed description
Hepatic impairment is a common co-morbidity in cancer patients, particularly in those with extensive liver metastases. Decreased drug clearance as a result of impaired liver function may lead to increased systemic exposure and possibly greater toxicity. As many chemotherapeutic agents are metabolized by the liver, treatment options tend to be limited in patients with severe hepatic impairment, even in the presence of good performance status and adequate other organ function. Cisplatin is an active chemotherapeutic agent with broad spectrum activity that can safely be administered in severe hepatic impairment. Cisplatin has been combined safely with full dose oral TS-1 with good efficacy in a spectrum of solid tumors in patients with adequate renal and hepatic function.
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the United States National Cancer Institute organ dysfunction working group [NCI-ODWG] criteria for hepatic dysfunction.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TS-1 combined with cisplatin | Experimental | Drug: TS-1 combined with cisplatinEligible patients will be stratified by degree of liver dysfunction into 4 cohorts, in accordance to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must fulfill ALL the following inclusion criteria
- Age 18 years.
- Histologic or cytologic diagnosis of carcinoma, that is either refractory to standard therapy or has no available therapies.
- Measurable disease using the RECIST v1.1 criteria
- ECOG performance 0 or 1.
Key exclusion criteria (17 listed)
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Treatment of a small molecule targeted agents ≤ 2 weeks prior to starting study treatment
- Treatment within the last 30 days with any investigational drug.
- Radiotherapy ≤4 weeks prior to starting study treatment or who have not recovered from radiotherapy-related toxicities. Limited field palliative radiotherapy ≤ 2 weeks prior to starting study treatment is allowed
- Major surgery within 28 days of study drug administration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TS-1 combined with cisplatinCisplatin 60mg/m2, day 1, every 21 days Oral TS-1 30mg/m2 bd, days 1-14, every 21 days (absolute dose of oral TS-1 will be 40-60mg bd days 1-14, every 21 days, depending on body surface area) | Drug | TS-1 combined with cisplatin |
Primary outcome
Efficacy evaluations: Disease status
Time frame: Radiological evaluation of tumor status every 2 cycles of cisplatin and oral TS-1 from baseline until documented disease progression; assessed up to 12 months
Efficacy evaluations will be performed using the RECIST v1.1 criteria Measurable disease: Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of 10mm on CT scan Malignant lymph node: ≥15mm in short axis on CT scan Non-measurable disease: All other lesions, including small lesions (longest diameter <10mm or pathological lymph nodes with >10 to <15mm short axis) as well as truly non-measurable lesions
Efficacy Evaluation: Timing
Time frame: 5 years
The duration of tumor response is measured from the date of enrollment until the first date of documented disease progression or death due to any cause, whichever occurs first.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 15075664Schoffski P. The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors. Anticancer Drugs. 2004 Feb;15(2):85-106. doi: 10.1097/00001813-200402000-00001.
- Background: PubMed 25862350Yamamoto D, Iwase S, Tsubota Y, Ariyoshi K, Kawaguchi T, Miyaji T, Sueoka N, Yamamoto C, Teramoto S, Odagiri H, Kitamura K, Nagumo Y, Yamaguchi T. Randomized study of orally administered fluorinated pyrimidines (capecitabine versus S-1) in women with metastatic or recurrent breast cancer: Japan Breast Cancer Research Network 05 Trial. Cancer Chemother Pharmacol. 2015 Jun;75(6):1183-9. doi: 10.1007/s00280-015-2738-3. Epub 2015 Apr 11.
- Background: PubMed 26617202Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. doi: 10.1016/S1470-2045(15)00411-8. Epub 2015 Nov 27.
- Derived from this study: PubMed 42964102Gwee YX, Wong ALA, Goh BC, Soo RA, Yong WP, Tan DSP, Chee CE, Lim SE, Ang Y, Huang Y, Chong WQ, Lim J, Chan G, Ngoi N, Ow S, Wong R, Sooi K, Choo J, Lee SC. Prospective evaluation of combination oral S-1 and intravenous cisplatin in cancer patients with severe hepatic dysfunction - a feasibility, safety, and pharmacokinetic study. Front Oncol. 2026 Oct 16;16:1948986. doi: 10.3389/fonc.2026.1948986. eCollection 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TS-1 combined with cisplatin in people with Cancer and Liver Dysfunction, run by National University Hospital, Singapore at 2 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy evaluations: Disease status (time frame: Radiological evaluation of tumor status every 2 cycles of cisplatin and oral TS-1 from baseline until documented disease progression; assessed up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03519074, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.