Phase Ib/IIa, Two-stage Trial of ABI-007 Plus S-1 as Second-line Chemotherapy in Advanced Gastric Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Nanoparticle Albumin-Bound Paclitaxel
The study evaluate 3 dose level of nab-paclitaxel:100 mg /m2;125 mg /m2;80 mg /m2;
干预措施: Nanoparticle Albumin-Bound Paclitaxel (Drug)
结局指标
主要结局
adverse events
时间窗: during the treatment in the hosptital,an expected average of 3 weeks
participants will be followed for the duration of hospital stay, an expected average of 3 weeks
Objective response rate
时间窗: 6 weeks
CT/MRI will be performed every 2 cycles of treatment for efficacy evaluation
次要结局
- progression free survival(1 year)
- overall survival of participants(2 years)
- biomarkers(6 weeks)
研究者
Shen Lin
PRO.
Peking University