Gastric Cancer
Conditions
Keywords
Gastric Cancer, Cetuximab, EMD271786, TS-1, Cisplatin
Brief summary
This open-label, single-arm, multicenter, Phase 2 trial will treat at least 40 participants with advanced gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction (GEJ) who have not previously received systemic chemotherapy for this setting. All eligible participants will receive the combination of cetuximab plus S-1 (a combination of tegafur, gimeracil, and oteracil) and cisplatin.
Interventions
DRUGCetuximab
Single first dose of cetuximab 400 milligram per square meter (mg/m\^2) will be administered intravenously followed by once weekly subsequent intravenous infusion of cetuximab 250 mg/m\^2 in each 5-week treatment cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
DRUGCisplatin
Cisplatin 60 mg/m\^2 will administered as intravenous infusion on Day 8 of each 5-week cycle maximum up to 8 cycles until disease progression, unacceptable toxicity, or withdrawal of consent
DRUGS-1
S-1, a combination of tegafur, gimeracil, and oteracil will be administered intravenously at a dose of 40 to 60 mg/m\^2 orally twice daily for first three consecutive weeks of 5-week cycle until disease progression, unacceptable toxicity, or withdrawal of consent.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent and agreement with medically accepted contraception (in participants with conception potential) are obtained * Japanese participants aged greater than or equal to 20 years * Histologically confirmed adenocarcinoma of the stomach or GEJ (adenocarcinomas of the esophagogastric junction types I to III according to Siewert's classification) in Stage M0 (unresectable advanced) or Stage M1 (unresectable metastatic) of the disease * Archived tumor material sample for at least subsequent standardized epidermal growth factor receptor (EGFR) expression and Kirsten-rat sarcoma (KRAS) mutation assessments * At least one radiographically documented measurable lesion in a previously non-irradiated area according to the RECIST v 1.0 * Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0 to 1 * Estimated life expectancy greater than 12 weeks * Renal, liver and hematopoietic function as defined in the protocol. * Sodium and potassium within normal limits or as defined in the protocol * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Prior therapies: prior treatment with an antibody or molecule targeting EGFR- and/or vascular endothelial growth factor (VEGF) receptor-related signaling pathways; chemotherapies; or radiotherapies, major surgeries, and any investigational drugs in the 30 days before the start of trial treatment * Concurrent chronic systemic immune or hormone therapy not indicated in this trial protocol any contraindication to treatment with cetuximab and cisplatin, or any treatments with prohibited concomitant drugs * Brain metastasis and/or leptomeningeal disease * Clinically relevant coronary artery disease (New York Heart Association \[NYHA\] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia * Chronic diarrhea or short bowel syndrome * Known Human Immunodeficiency Virus (HIV) infection, active or chronic carrier of hepatitis B virus (HBV) (HBV antigen positive or HBV deoxyribonucleic acid (DNA) positive) or hepatitis C virus (HCV) (HCV antibody positive) * Pregnancy or lactation period * Concurrent treatment with a non-permitted drug (any other chemotherapy, systemic anticancer therapy or immunotherapy) * Previous malignancy other than gastric cancer in the last 5 years Medical or psychological conditions that would not permit the participant to complete the trial or sign the Informed Consent Form (ICF) * Legal incapacity or limited legal capacity * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) Rate - Independent Review Committee (IRC) Assessments | Evaluations were performed every 6 weeks until disease progression, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012) | The best overall response rate is defined as the percentage of participants having achieved confirmed complete response plus partial response as the best overall response according to radiological assessments (based on Response Evaluation Criteria in Solid Tumors version 1.0 \[RECIST v 1.0\] criteria). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments | Time from start of treatment to disease progression, death or last tumor assessment, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012) | The PFS time is defined as the duration from start of treatment until radiological progression (based on RECIST v 1.0 criteria) or death due to any cause within 60 days of the last tumor assessment or start of treatment. Participants without event are censored on the date of last tumor assessment. |
Countries
Germany
Participant flow
Recruitment details
First/last participant (informed consent): 29 June 2011/16 January 2012; Clinical data cut-off: 14 August 2012; Study completion: 13 May 2013.
Pre-assignment details
Enrolled: 41 screened for eligibility; 1 excluded (non-fulfillment of inclusion or exclusion criteria) and 40 participants included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Plus Cisplatin Plus S-1 Cetuximab once weekly (initial dose 400 milligram per square meter \[mg/m\^2\] followed by subsequent 250 mg/m\^2 intravenous infusion), cisplatin (60 mg/m\^2 intravenous infusion on Day 8 of 5-week cycle maximum up to 8 cycles) and S-1, a combination of tegafur, gimeracil, and oteracil (40 to 60 mg/m\^2 orally twice daily for first three consecutive weeks of 5-week cycle) was administered until disease progression, unacceptable toxicity, or withdrawal of consent. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ongoing at data cut-off date | 8 |
Baseline characteristics
| Characteristic | Cetuximab Plus Cisplatin Plus S-1 |
|---|---|
| Age Continuous | 61.7 years STANDARD_DEVIATION 10.09 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 15 / 40 |
Outcome results
Primary
Best Overall Response (BOR) Rate - Independent Review Committee (IRC) Assessments
The best overall response rate is defined as the percentage of participants having achieved confirmed complete response plus partial response as the best overall response according to radiological assessments (based on Response Evaluation Criteria in Solid Tumors version 1.0 \[RECIST v 1.0\] criteria).
Time frame: Evaluations were performed every 6 weeks until disease progression, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012)
Population: ITT population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus Cisplatin Plus S-1 | Best Overall Response (BOR) Rate - Independent Review Committee (IRC) Assessments | 40 percentage of participants |
Secondary
Median Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments
The PFS time is defined as the duration from start of treatment until radiological progression (based on RECIST v 1.0 criteria) or death due to any cause within 60 days of the last tumor assessment or start of treatment. Participants without event are censored on the date of last tumor assessment.
Time frame: Time from start of treatment to disease progression, death or last tumor assessment, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012)
Population: ITT population included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus Cisplatin Plus S-1 | Median Progression-free Survival (PFS) Time - Independent Review Committee (IRC) Assessments | 5.6 months |