Trial of ABI-007 Plus S-1 as Second-line Chemotherapy in Advanced Gastric Cancer Patients

This study is a two-stage design. Stage 1

The investigator should evaluate two recommend dose and tolerability of nab-paclitaxel plus S-1 after one course of treatment as 3+1 design:

nab-paclitaxel should be given intravenously on days 1 and 8 at a dose as follows, Treatment should be repeated every 3 weeks: Treatment arm A：125 mg /m2; Treatment arm B：100 mg /m2; Treatment arm C: 80 mg /m2; S-1 should be given orally twice a day as follows for 14 consecutive days, followed by a 1-week rest. Treatment should be repeated every 3 weeks. BSA < 1.5 m2，40mg，bid;BSA ≥ 1.5 m2，50mg，bid.

The investigator should determine whether to continue the original regimen; compare the safety and pharmacokinetic results with original profile of combination therapy to select the best therapy programs (RD, recommended dose).

Stage 2 According to two-stage design (Simon,1989), re-entry subjects to the recommended dose group to a total of 25 valid cases. If 11 patients achieve response, then enter the second phase of total 66 patients.

Inclusion criteria

• Signed informed consent form
• Age 18-75 years;
• Histologically or cytologically confirmed gastric cancer;
• Advanced or recurrent, metastatic disease;
• Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1;
• Life expectancy of at least 12 weeks;
• At least have one measurable disease(according to RECIST, Response Evaluation Criteria in Solid Tumors )
• Subjects who have received one prior regimen for gastric carcinoma and developed disease progression or recurrence within 6 months after the end of systemic adjuvant treatment. The regimen must have contained fluorouracil(e.g. 5-FU,capecitabine) and/or cisplatin;
• Haematopoietic status:

• Absolute neutrophil count > 1.5 x 109/L,
• Platelet count > 90 x 109/L,
• Hemoglobin at least 9 g/dl,
• Hepatic status:

• Bilirubin ≤ 1.5 x upper limit of normal (ULN),
• AST and ALT ≤ 2.5 times ULN(no liver metastasis), ≤5 times ULN(with liver metastasis)
• Renal status:

• Creatinine ≤1.5 times ULN or calculated creatinine clearance, using the Cockcroft-Gault formula, ≥40 mL/min;
• Able to swallow and retain oral medication；without malabsorption syndrome, or disease significantly affecting gastrointestinal function, such as ulcerative colitis and Crohn's disease;
• Cardiovascular: Baseline LVEF 50% measured by echocardiography (ECHO) ;
• Negative serum pregnancy test (For women of childbearing potential);Fertile patients must use effective contraception.

Exclusion criteria

• Received any prior treatment including taxane or S-1;
• Concurrent systemic anti-cancer therapy (immunotherapy, biologic therapy, hormone therapy, etc ); received treatment with an investigational agent or participation in another therapeutic clinical trial within 4 weeks;
• Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2; peripheral neuropathy of grade 2 or greater
• Symptomatic brain metastasis;
• Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, uncontrolled hypertension (≥ 180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen;
• History of other malignancy. However, subjects with a past or current history of completely resected basal and squamous cell carcinoma of the skin or successfully treated in situ carcinoma of the cervix are eligible
• Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
• Active or uncontrolled infection;
• Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
• Pregnant or lactating women.