Clinical trial NCT01396707: Trastuzumab in Combination With Capecitabine and Oxaliplatin(XELOX) in Patients With Advanced Gastric Cancer(AGC): Her+XELOX
Official title: A Phase II Study of Trastuzumab in Combination With Capecitabine and Oxaliplatin (XELOX) in Patients With Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic or Recurrent Gastric Adenocarcinoma
Her-2 Positive Gastric Cancer
Keywords: HER2
Trastuzumab
XELOX
PHASE 2
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2011-07-19
Enrollment: 55
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicentre, prospective phase II trial designed to evaluate the efficacy and safety of trastuzumab in combination with capecitabine and oxaliplatin as first-line therapy in patients with recurrent and/or metastatic HER2 positive adenocarcinoma of the stomach or gastro-oesophageal junction.

Detailed description: Patients will be administered 6 cycles of combination chemotherapy, unless withdrawn earlier due to unacceptable toxicity, disease progression, or consent withdrawal. Patients will continue to be treated with trastuzumab alone until disease progression, unacceptable toxicity or consent withdrawal after finishing a maximum 6 cycles of combination chemotherapy.

Eligibility criteria: 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), assessed using imaging techniques (CT or MRI).
3. HER2 positive tumour (primary tumour or metastasis) defined as either IHC2+ and FISH+ or IHC3+ according to the gastric cancer scoring system for HER2
4. ECOG Performance status 0, 1 or 2
5. Life expectancy of at least 3 months.
6. Male or female. Age over 20 year.
7. Signed informed consent.

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 platinum 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 tube).
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 over grade 2 NCI-CTCAE.
5. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
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 dyspnea 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.
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 metastatic site peripherally and patient recovered from any acute toxicity).
21. Major surgery within 4 weeks of start of study treatment, without complete recovery.
22. History of HIV infection, Patients with known active infection with HBV, or HCV.
23. Known hypersensitivity to any of the study drugs.

Primary outcomes:
measure: Overall response rate
timeFrame: 1 year
Secondary outcomes:
measure: Duration of response
timeFrame: 1 year
measure: Time to progression
timeFrame: 1 year
measure: Progression free survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Yoon-Koo Kang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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