Metastatic HER2-positive adenocarcinoma of the stomach or gastro-esophageal junction. MedDRA version: 16.0 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.0 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Herceptin®
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: RO0452317
Other descriptive
Sponsors
F.Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female. Age = 18 years. 4. Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least lung or liver or both 5. Measurable disease according to RECIST 1.1. or non-measurable evaluable disease 6. At least 2 organs involved by metastatic gastric tumor (including at least lung or liver or both) in addition to the site of the primary tumor. Metastasis in distant lymph nodes, peritoneal metastasis, malignant pleural effusion, etc. count as 'organs' in this context. 7. HER2 positive (defined as either IHC3+ or IHC2+/ISH+, with ISH positivity defined as a ratio of >=2.0 of HER2 gene copy number/number of signals for CEP 17) primary or metastatic tumor, as assessed by central laboratory 8. CCR >=45 ml/min 9. ECOG PS =2 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 263 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 142
Exclusion criteria
Exclusion criteria: 1. Previous chemotherapy for locally advanced or metastatic disease 2. Prior gastrectomy 3. Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent 4. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g., patients with a jejunostomy probe, gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine, as capecitabine is an orally administered drug. 6. Residual relevant toxicity resulting from previous therapy 11. History of documented congestive heart failure; angina pectoris requiring medication; electrocardiogram (ECG) evidence of trans-mural myocardial infarction; poorly controlled hypertension (systolic blood pressure (BP) > 180 mmHg or diastolic BP>100 mm Hg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias 12. Baseline LVEF< 50%, documented by echocardiography, MUGA scan, or cardiac MRI.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the duration of overall survival in patients who are randomized at enrollment to treatment with one of two trastuzumab dosing regimens (loading dose of 8mg/kg) followed by either 6mg/kg or 10mg/kg maintenance doses given every 3 weeks, plus cisplatin and capecitabine.;Secondary Objective: • To compare the duration of overall survival (OS) in patients on the two trastuzumab treatment arms who are found to have trastuzumab Cmin values < 12 µg/mL on Cycle 1 Day 21. • To assess trastuzumab concentrations during treatment Cycle 1 and trastuzumab Cmin(Day 21) values in additional treatment cycles through Cycle 11 (ie, pre-dose concentration before Cycle 12) or until disease progression (whatever occurs first) for the two dosing regimens. • To evaluate the safety and tolerability of trastuzumab for the two dosing regimens. • To compare the duration of progression-free survival (PFS) and the overall objective response rate (ORR) in patients on the two trastuzumab treatment arms who are found to have trastuzumab Cmin values < 12 µg/mL on treatment Cycle 1 Day 21.;Primary end point(s): The study primary endpoint will be OS duration in all randomized patients.;Timepoint(s) of evaluation of this end point: This is event driven, when approximately 379 deaths have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints will be OS in patients with Cycle 1 Cmin <12 ug/ml, Pharmacokinetic analyses , safety and tolerability in the two dosing regimens; duration of progression-free survival (PFS) and the overall objective response rate (ORR) in patients who are found to have trastuzumab Cmin values < 12 µg/mL on treatment Cycle 1 Day 21.;Timepoint(s) of evaluation of this end point: This is event driven, when approximately 379 deaths have occurred. | — |
Countries
Australia, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Czech Republic, Germany, Hungary, India, Italy, Korea, Republic of, Mexico, New Zealand, Panama, Peru, Philippines, Poland, Portugal, Russian Federation, Serbia, South Africa, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed