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

Phase Ib/IIa, Two-stage Trial of ABI-007 Plus S-1 as Second-line Chemotherapy in Advanced Gastric Cancer Patients

Gastric cancer have poor prognosis and majority of patients resistant to 5-FU/DDP based first-line chemotherapy in China. There was no recommended second-line chemotherapy for advanced gastric cancer. Taxane is promising in gastric cancer. Nanoparticle Albumin-Bound Paclitaxel (Abraxane，ABI-007) has good convenience to use and been approved in breast cancer in many countries. The investigator then initiated a prospective phase Ib/IIa clinical trial with nab-paclitaxel plus TS-1 as the second-line treatment in advanced gastric cancer to observe the safety and efficacy.

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:

1. Signed informed consent form

2. Age 18-75 years;

3. Histologically or cytologically confirmed gastric cancer;

4. Advanced or recurrent, metastatic disease;

5. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1;

6. Life expectancy of at least 12 weeks;

7. At least have one measurable disease(according to RECIST, Response Evaluation Criteria in Solid Tumors )

8. 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;

9. Haematopoietic status:

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

10. 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)

11. Renal status:

    - Creatinine ≤1.5 times ULN or calculated creatinine clearance, using the Cockcroft-Gault formula, ≥40 mL/min;

12. Able to swallow and retain oral medication；without malabsorption syndrome, or disease significantly affecting gastrointestinal function, such as ulcerative colitis and Crohn's disease;

13. Cardiovascular: Baseline LVEF 50% measured by echocardiography (ECHO) ;

14. Negative serum pregnancy test (For women of childbearing potential);Fertile patients must use effective contraception.

Exclusion Criteria:

1. Received any prior treatment including taxane or S-1;
2. 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;
3. Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2; peripheral neuropathy of grade 2 or greater
4. Symptomatic brain metastasis;
5. 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;
6. 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
7. Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
8. Active or uncontrolled infection;
9. Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
10. Pregnant or lactating women.