Gastric CancerPhase 2NCT01228045
A Study of Trastuzumab in Combination With TS-ONE & Cisplatin in First-line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer
A Phase 2 study testing Trastuzumab in Combination with TS-ONE and cisplatin in people with Gastric Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
The investigators hypothesis is that the combination of TS-ONE with cisplatin and trastuzumab is safe and as effective as combination treatment for HER2 positive gastric cancer. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Gastric Cancer
- What is being tested?
- Trastuzumab in Combination with TS-ONE and cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSingapore
- Study dates
- Feb 2011to Dec 2016
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically proved adenocarcinoma of advanced gastric cancer.
- Patients who have HER2-positive cancer confirmed with IHC and/or FISH.
- Patients with proved presence of measurable (RECIST criteria) lesions within 28 days before enrollment.
- Patients without prior treatment (ex. radiotherapy, chemotherapy, hormonal therapy): Patients who completed adjuvant chemotherapy more than 180 days before may be enrolled but those who received TS-ONE or cisplatin shall be excluded.
- Patients with the following function of bone marrow, liver and kidney based on the laboratory tests measured within 14 days before enrollment. Hemoglobin >= 8.0 g/dL leukocytes >=3,000/mcL absolute neutrophil count >=1,500/mcL platelets >=100,000/mcL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT)=<2.5 X institutional upper limit of normal ALP < twice of the upper limit of normal, creatinine within normal institutional limits or creatinine clearance >=60 mL/min for patients with creatinine levels above institutional normal (When AST(GOT), ALT(GPT) and ALP do not satisfy the conditions above and these values are considered to be caused by cancer, the decision is based on the discretion of investigators or co-investigators) Creatinine clearance can be estimated using Cockcroft-Gault formula man: Ccr (mL/min) = body weight (kg) x (140 - age)/(72 x serum creatinine (mg/dL)), woman: Ccr = male Ccr x 0.85].
- ECOG performance status =<2 (Karnofsky >60%; see Appendix A).
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- Patients who are expected to survive more than 3 months after enrollment.
- Age >= 21.
- Patients of adequate oral intake.
- Patients who underwent electrocardiography within 28 days before enrollment.\
- Patients who give written informed consent for additional endoscopy to obtain fresh frozen tissue biopsies for translational studies at 2 time points pre-1st cycle of chemotherapy and at progression.
- Patients who give written informed consent for enrollment into trial.
Who cannot join
- Patients for whom TS-ONE or cisplatin or trastuzumab is contraindicated.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to TS-ONE, cisplatin and trastuzumab.
- Patients receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Baseline heart function LVEF (Left Ventricular Ejection Fraction) < 50%.
- Patients with serious (ex. inpatient care is needed) complications (ex. intestinal paralysis, intestinal occlusion, interstitial pneumonia or pulmonary fibrosis, poorly-controlled diabetes, renal failure or hepatic cirrhosis).
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- Patients with massive ascites (moderate or higher, beyond the pelvic cavity and retention on the anterior surface of the liver on CT) or pleural effusion retention.
- Patients with extensive bone metastasis.
- Patients with known brain metastases.
- Patients with fresh bleeding from the digestive tract which needs repeated blood transfusion.
- Patients with diarrhea (4 or more times per day or watery diarrhea).
- Patients with simultaneously active multiple cancer.
- Pregnant or lactating female.
- Patients with reproductive potential who refuse to use an adequate means of contraception (including male patients).
- Other patients evaluated to be inadequate to participate in the study by co-investigators.
- No informed consent for either treatment regimen or collection of fresh frozen biopsy tissue for translational studies.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study of Trastuzumab in Combination With TS-ONE and Cisplatin in First-line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer.
The investigators hypothesis is that the combination of TS-ONE with cisplatin and trastuzumab is safe and as effective as combination treatment for HER2 positive gastric cancer.
Read the detailed description
Gastric carcinoma is the second most common cause of cancer death world-wide. Approximately 875,000 patients are diagnosed world-wide with gastric cancer each year. Gastric cancer is often diagnosed at an advanced stage1. At diagnosis, while some patients have gastric carcinoma that extends within loco-regional confines and can undergo a curative resection, many patients cannot undergo curative resection. Gastric cancer continues to pose a major medical challenge.
While advanced gastric carcinoma is incurable, chemotherapy can have a palliative effect in symptomatic patients. Chemotherapy improves outcome compared to best supportive care in gastric cancer. Various chemotherapeutic agents including 5-FU, mitomycin, etoposide, cisplatin, irinotecan and the taxanes, have demonstrated activity as monotherapy. Combination chemotherapy has been shown to have better survival outcomes than single agent chemotherapy Standard chemotherapy for advanced gastric carcinoma includes a fluoropyrimidine and platinum -based combination chemotherapy.
- Conditions
- Gastric Cancer
- Being tested
- Trastuzumab in Combination with TS-ONE and cisplatin
- Keywords
- Patients with histologically proved adenocarcinoma of advanced gastric cancer
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab in Combination with TS-ONE and cisplatinDrug
Subjects will receive treatment that combined TS-ONE, cisplatin and trastuzumab every 3 weeks in this study. This 3 weeks period of time is called a cycle. The cycle will be repeated until subject experience disease progression or unbearable toxicities or they choose to withdraw from the study. Each cycle is numbered in order.
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab in Combination with TS-ONE and cisplatin | Experimental | The initial dose of cisplatin is fixed to be 60 mg/m2 and intravenously administered over 1 hour on day 1 of the cycle. TS-ONE is orally administered consecutive 14-day followed by 7-day rest. The initial standard dose of TS-ONE is determined based on the body surface area tabled below. Trastuzumab is intravenously administered with the loading dose of 8 mg/kg followed by maintenance dose of 6mg/kg in day 1 of each cycle. The study treatments are repeated every 3 weeks. Study treatment can continue until PD, but cisplatin can be skipped or discontinued if patients experienced unbearable toxicity which comes from cisplatin. Receives: Drug: Trastuzumab in Combination with TS-ONE and cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Measured: Fom the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
Secondary outcomes (6)
Progression free survival (PFS)
Measured: Time from registration until objective tumor progression or death for any reason that occurs by the end of the study.
Overall survival (OS)
Measured: Time from registration to the date of death.
Time to Treatment Failure (TTF)
Measured: Time from registration until discontinuation of treatment for any reason (including progression of disease, treatment toxicity, and death).
Clinical Benefit Rate (CBR)
Measured: proportion of patients with confirmed CR, PR, and SD over 24 weeks.
Duration of Response (DR)
Median time will be estimated using the Kaplan Meier method. 95% confidence interval of the median time will be estimated.
Measured: Time from first assessment of CR or PR until the first date of PD or death within 60 days of the last tumor assessment or registration, whichever is first.
Safety Evaluations
AEs will be coded according to the Medical Dictionary for Regulatory Activities Terminology (MedDRA) and the severity of the toxicities will be graded according to the NCI CTCAE criteria, version 3.0, where applicable. Concomitant medications will be coded according to WHO Medication Dictionary for Concomitant Medication.
All AEs will be summarized (incidence) and listed by the System Organ Class (SOC), preferred term, toxicity/severity grade, and causal relationship. In addition, separate summaries of SAEs and Grade 3 or 4 AEs will be presented. Cardiac AEs including asymptomatic LVEF drops will also be summarized in separate tables.
Hematological and chemistry laboratory parameters will be graded according to the NCI CTCAE criteria, where applicable. Absolute values and changes from baseline will be summarized by cycle. In addition, worst severity grade will also be summarized.
Measured: Focus on AEs and laboratory assessments.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study startFeb 2011
- Primary completionDec 2014
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastric 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Centre, Singapore
- Responsible party
- Sponsor
- Investigators
- Wei Peng Yong, MRCP, MB ChB, Principal investigator, National University Hospital Singapore, NUHS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01228045
- Sponsor's protocol ID
- S1/CDDP/Her
- Status last verified
- Jun 2016
- First submitted
- 21 Oct 2010
- Last updated
- 22 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132-9. doi: 10.1126/science.2999974.
PubMed 2999974Press MF, Pike MC, Chazin VR, Hung G, Udove JA, Markowicz M, Danyluk J, Godolphin W, Sliwkowski M, Akita R, et al. Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res. 1993 Oct 15;53(20):4960-70.
PubMed 8104689
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Trastuzumab in Combination With TS-ONE and Cisplatin in First-line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer.
- ClinicalTrials.gov ID
- NCT01228045
- Acronym / sponsor ID
- S1/CDDP/Her
- Conditions
- Gastric Cancer
- Keywords
- Patients with histologically proved adenocarcinoma of advanced gastric cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- National Cancer Centre, Singapore
- Study start
- Feb 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2016 (estimated)
- First posted
- 25 Oct 2010 (estimated)
- 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 investigators hypothesis is that the combination of TS-ONE with cisplatin and trastuzumab is safe and as effective as combination treatment for HER2 positive gastric cancer.
Detailed description
Gastric carcinoma is the second most common cause of cancer death world-wide. Approximately 875,000 patients are diagnosed world-wide with gastric cancer each year. Gastric cancer is often diagnosed at an advanced stage1. At diagnosis, while some patients have gastric carcinoma that extends within loco-regional confines and can undergo a curative resection, many patients cannot undergo curative resection. Gastric cancer continues to pose a major medical challenge.
While advanced gastric carcinoma is incurable, chemotherapy can have a palliative effect in symptomatic patients. Chemotherapy improves outcome compared to best supportive care in gastric cancer. Various chemotherapeutic agents including 5-FU, mitomycin, etoposide, cisplatin, irinotecan and the taxanes, have demonstrated activity as monotherapy. Combination chemotherapy has been shown to have better survival outcomes than single agent chemotherapy Standard chemotherapy for advanced gastric carcinoma includes a fluoropyrimidine and platinum -based combination chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab in Combination with TS-ONE and cisplatin | Experimental | Drug: Trastuzumab in Combination with TS-ONE and cisplatinThe initial dose of cisplatin is fixed to be 60 mg/m2 and intravenously administered over 1 hour on day 1 of the cycle. TS-ONE is orally administered consecutive 14-day followed by 7-day rest. The initial standard dose of TS-ONE is determined based on the body surface area tabled below. Trastuzumab is intravenously administered with the loading dose of 8 mg/kg followed by maintenance dose of 6mg/kg in day 1 of each cycle. The study treatments are repeated every 3 weeks. Study treatment can continue until PD, but cisplatin can be skipped or discontinued if patients experienced unbearable toxicity which comes from cisplatin. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with histologically proved adenocarcinoma of advanced gastric cancer.
- Patients who have HER2-positive cancer confirmed with IHC and/or FISH.
- Patients with proved presence of measurable (RECIST criteria) lesions within 28 days before enrollment.
- Patients without prior treatment (ex. radiotherapy, chemotherapy, hormonal therapy): Patients who completed adjuvant chemotherapy more than 180 days before may be enrolled but those who received TS-ONE or cisplatin shall be excluded.
- Patients with the following function of bone marrow, liver and kidney based on the laboratory tests measured within 14 days before enrollment. Hemoglobin >= 8.0 g/dL leukocytes >=3,000/mcL absolute neutrophil count >=1,500/mcL platelets >=100,000/mcL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT)=<2.5 X institutional upper limit of normal ALP < twice of the upper limit of normal, creatinine within normal institutional limits or creatinine clearance >=60 mL/min for patients with creatinine levels above institutional normal (When AST(GOT), ALT(GPT) and ALP do not satisfy the conditions above and these values are considered to be caused by cancer, the decision is based on the discretion of investigators or co-investigators) Creatinine clearance can be estimated using Cockcroft-Gault formula man: Ccr (mL/min) = body weight (kg) x (140 - age)/(72 x serum creatinine (mg/dL)), woman: Ccr = male Ccr x 0.85].
Key exclusion criteria (16 listed)
- Patients for whom TS-ONE or cisplatin or trastuzumab is contraindicated.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to TS-ONE, cisplatin and trastuzumab.
- Patients receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Baseline heart function LVEF (Left Ventricular Ejection Fraction) < 50%.
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 |
|---|---|---|
| Trastuzumab in Combination with TS-ONE and cisplatinSubjects will receive treatment that combined TS-ONE, cisplatin and trastuzumab every 3 weeks in this study. This 3 weeks period of time is called a cycle. The cycle will be repeated until subject experience disease progression or unbearable toxicities or they choose to withdraw from the study. Each cycle is numbered in order. | Drug | Trastuzumab in Combination with TS-ONE and cisplatin |
Primary outcome
Overall Response Rate (ORR)
Time frame: Fom the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
6 secondary outcomes
Progression free survival (PFS)
Time frame: Time from registration until objective tumor progression or death for any reason that occurs by the end of the study.
Overall survival (OS)
Time frame: Time from registration to the date of death.
Time to Treatment Failure (TTF)
Time frame: Time from registration until discontinuation of treatment for any reason (including progression of disease, treatment toxicity, and death).
Clinical Benefit Rate (CBR)
Time frame: proportion of patients with confirmed CR, PR, and SD over 24 weeks.
Duration of Response (DR)
Time frame: Time from first assessment of CR or PR until the first date of PD or death within 60 days of the last tumor assessment or registration, whichever is first.
Safety Evaluations
Time frame: Focus on AEs and laboratory assessments.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2016.
- Background: PubMed 2999974Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132-9. doi: 10.1126/science.2999974.
- Background: PubMed 8104689Press MF, Pike MC, Chazin VR, Hung G, Udove JA, Markowicz M, Danyluk J, Godolphin W, Sliwkowski M, Akita R, et al. Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res. 1993 Oct 15;53(20):4960-70.
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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.
Wei Peng Yong, MRCP, MB ChB principal investigator
National University Hospital Singapore, NUHS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab in Combination with TS-ONE and cisplatin in people with Gastric Cancer, run by National University Hospital, Singapore at 1 site 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 16 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 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Overall Response Rate (ORR) (time frame: Fom the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented). 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 NCT01228045, which also lists 2 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 22 Jun 2016.