An open-label randomized multicentre phase III study of trastuzumab in combination with a fluoropyrimidine and cisplatin versus chemotherapy alone as first-line therapy in patients with HER2 positive advanced gastric cancer.

• Conditions: Advanced gastric cancer; MedDRA version: 7.1Level: PTClassification code 10017767

• Registration Number: EUCTR2005-000387-39-BE
• Lead Sponsor: Hoffmann-La Roche Ltd/Inc/AG/Roche Global Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08-23
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 584

Inclusion Criteria

Disease Specific Inclusion Criteria:
1. Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy.
2. Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST), or non-measurable evaluable disease, assessed using imaging techniques (CT or MRI).
3. HER2 positive tumour (primary tumour or metastasis) as assessed by the central laboratory. (Both IHC and FISH will be performed on all patients in the central laboratory.)
4. ECOG Performance status 0, 1 or 2.
5. Life expectancy of at least 3 months.
General Inclusion Criteria:
6. Male or female. Age greater or equal to 18 years.
7. Signed informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Cancer-Related Exclusion Criteria:
1. Previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrolment into the study; adjuvant/neoadjuvant therapy with platin is not allowed*).
2. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g. patients with partial or total gastrectomy can enter the study, but not those with a jejunostomy probe). This is pertinent to those patients who are to receive capecitabine, in view of capecitabine being an orally administered study drug (whereas 5-FU is given intravenously).
3. Patients with active (significant or uncontrolled) gastrointestinal bleeding.
4. Residual relevant toxicity resulting from previous therapy (with the exception of alopecia), e.g. neurological toxicity ? grade 2 NCI-CTCAE.
5. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
Haematological, Biochemical and Organ Function:
6. Neutrophil count < 1.5 × 109/L, or platelet count < 100 × 109/L.
7. Serum bilirubin > 1.5 × upper limit of normal (ULN); or, AST or ALT > 2.5 × ULN (or > 5 × ULN in patients with liver metastases); or, alkaline phosphatase > 2.5 × ULN (or > 5 × ULN in patients with liver metastases, or > 10 × ULN in patients with bone but no liver metastases); or, albumin < 25 g/L.
8. Creatinine clearance < 60 mL/min.
Other Study Drug-Related Exclusion Criteria:
9. History of documented congestive heart failure; angina pectoris requiring medication; evidence of transmural myocardial infarction on ECG; poorly controlled hypertension (systolic BP > 180 mmHg or diastolic BP > 100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias.
10. Baseline LVEF < 50% (measured by echocardiography or MUGA).
11. Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy.
12. Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed).
13. Clinically significant hearing abnormality.
14. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
General Exclusion Criteria:
15. History or clinical evidence of brain metastases.
16. Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes.
17. Positive serum pregnancy test in women of childbearing potential.
18. Subjects with reproductive potential not willing to use an effective method of contraception.
19. Received any investigational drug treatment within 4 weeks of start of study treatment.
20. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastastic site peripherally and patient recovered from any acute toxicity).
21. Major surgery within 4 weeks of start of study treatment, without complete recovery.
22. Patients with known active infection with HIV, HBV, or HCV. Patients with known HIV, HBV or HCV positivity are not allowed to participate in the PK assessments (pertinent to all patients randomized to trastuzumab arm of study).
23. Known hypersensitivity to any of the study drugs.
*Exceptionally 1-2 cycles of Cisplatin will be allowed as per discretion of the investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified