An Open-Label, Non-Randomized, Multicenter, Two-Stage, Phase 2 Study of S-1 in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 主要终点
- Overall Tumor Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to determine whether S-1 is effective in slowing tumor activity in participants with locally advanced or metastatic pancreatic cancer who have not had chemotherapy. The study is also looking at the safety of S-1.
详细描述
Locally advanced or metastatic pancreatic cancer is relatively unresponsive to chemotherapy. This is true for the nucleoside analogue gemcitabine, with a response rate of approximately 10%, as well as for 5-fluorouracil (5-FU). Even when gemcitabine is combined with other chemotherapeutic drugs or biological agents, the overall tumor response rate remains basically unchanged. S-1 is a new generation oral fluoropyrimidine that combines Tegafur (5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione [FT]), an oral prodrug of 5-FU, with two modulators, Gimeracil (5-chloro-2,4-dihydroxypyridine [CDHP]), which inhibits 5-FU degradation by dihydropyrimidine dehydrogenase (DPD) inhibition, and Oteracil potassium (Oxo), which inhibits 5-FU phosphorylation in the digestive tract. This combination of 3 compounds is designed to achieve enhanced antitumor activity while decreasing gastrointestinal toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has provided written informed consent.
- •Has histologically or cytologically confirmed locally advanced, unresectable or metastatic adenocarcinoma of the pancreas not amenable to curative radiotherapy or surgery.
- •Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (ie, lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm using spiral computed tomography [CT] scan).
- •Is able to take medications orally.
- •Is 18 years of age or older.
- •Has a Karnofsky Performance Status (KPS) ≥ 70%.
- •Has a life expectancy of ≥ 12 weeks.
- •Has adequate organ function as defined by the following criteria:
- •Transaminases AST (SGOT) and ALT (SGPT) ≤ 2.5 times the upper limit of normal (ULN). If liver function abnormalities are due to underlying liver metastasis, then AST (SGOT) and ALT (SGPT) may be ≤ 5 times ULN.
- •Total serum bilirubin ≤ 3.0 times ULN (if due to underlying liver metastasis, then total bilirubin may be ≤ 5 times ULN).
- •Absolute granulocyte count ≥ 1,500/mm3 (ie, ≥ 1.5 x 109/L by International Units [IU]).
- •Platelet count ≥ 100,000/mm3 (IU: ≥ 100 x 109/L).
- •Hemoglobin value ≥ 9.0 g/dL.
- •Calculated creatinine clearance ≥ 60 mL/min (based on serum creatinine) (Cockcroft-Gault85 formula)
- •Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
排除标准
- •Has had treatment with any of the following within the specified time frame prior to study drug administration:
- •Any prior anticancer chemotherapy.
- •Radiation therapy to a target lesion unless there was evidence of PD after radiotherapy (and this target lesion must not be the only site of measurable disease).
- •Any radiotherapy within the previous 3 weeks.
- •Any investigational agent received either concurrently or within the last 30 days.
- •Current enrollment in another clinical study with an investigational agent. Patients participating in surveys or observational studies are eligible to participate in this study.
- •Major surgery within the previous 3 weeks.
- •Symptomatic brain metastasis not controlled by corticosteroids.
- •Leptomeningeal metastasis.
- •Previous or concurrent malignancy other than pancreatic cancer except adequately treated carcinoma in-situ of the cervix or non-melanoma skin cancer.
- •Uncontrolled ascites requiring drainage at least twice a week.
- •Other serious illness or medical condition(s) including, but not limited to, the following:
- •Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class III or IV), angina pectoris, arrhythmias, or hypertension.
- •Active infection.
- •Known (at time of entry) gastrointestinal disorder, including malabsorption, chronic nausea, vomiting, or diarrhea, present to the extent that it might interfere with oral intake and absorption of study medication.
- •Poorly controlled diabetes mellitus.
- •Psychiatric disorder that may interfere with consent and/or protocol compliance.
- •Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
- •Is receiving a concomitant treatment with drugs interacting with S-
- •The following drugs are prohibited because there may be an interaction with S-1:
- •Sorivudine, uracil, cimetidine, folinic acid, and dipyridamole (may enhance S-1 activity).
- •Allopurinol (may diminish S-1 activity).
- •Phenytoin (S-1 may enhance phenytoin activity).
- •Flucytosine, a fluorinated pyrimidine antifungal agent (may enhance S-1 and flucytosine activity).
- •Is a pregnant or lactating female.
- •Has known sensitivity to 5-FU.
- •Is a patient with reproductive potential who refuses to use an adequate means of contraception (including male patients).
研究组 & 干预措施
S-1 30 mg/m^2
Participants received 30 milligrams per meter square (mg/m^2) of S-1 orally twice daily (BID) for 2 weeks (i.e., Day 1 to 14), followed by 1 week recovery period (i.e., Day 15 to 21; one cycle equaled 21 days), treatment was repeated every 3 weeks until death, progression of disease, occurrence of intolerable side effects, withdrawal of consent, or removal by Investigator, whichever comes first.
干预措施: S-1 (Drug)
结局指标
主要结局
Overall Tumor Response Rate (ORR)
时间窗: From first dose of study medication until disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 2 years 5 months
ORR was defined as the percentage of participants with objective evidence of partial response (PR) or complete response (CR) and was based on the best overall response across all cycles for each participant. Tumor response was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST). For target lesions response, CR was defined as the disappearance of all target lesions for at least 3 weeks and PR was defined as at least a 30% reduction in the sum of the longest diameters of the target lesions, taking as a reference the baseline sum of the longest diameters for at least 6 weeks. For non-target lesions, CR was defined the disappearance of all non-target lesions and normalization of tumor marker level for at least 6 weeks.
次要结局
- Disease Control Rate (DCR)(From first dose of study medication until disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 2 years 5 months)
- Change From Baseline in Pain Intensity(Baseline, at end of treatment (up to 2 years 5 months))
- Duration of Response (DR)(From first dose of study medication until disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 2 years 5 months)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAE)(From the first dose of study medication up to 30 days after the last dose of study medication, or until additional antitumor therapy had been introduced, whichever came first (approximately up to 2 years 6 months))
- Progression-free Survival (PFS)(From first dose of study medication until disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 2 years 5 months)
- Overall Survival (OS)(From first dose of study medication until disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 2 years 5 months)
- Number of Participants With Karnofsky Performance Status (KPS) Score - Shift From Baseline Score to Final Assessment Score(Baseline, at end of treatment (up to 2 years 5 months))
- Time to Tumor Progression (TTP)(From first dose of study medication until disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 2 years 5 months)