A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of S-1 and Oxaliplatin With or Without Ramucirumab as First-line Therapy Followed by Paclitaxel With Ramucirumab as Second-line Therapy in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 191
- 试验地点
- 2
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The main purpose of this study is to evaluate the effectiveness of S-1 and oxaliplatin with or without ramucirumab as first line therapy in participants with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a histopathologically or cytologically confirmed diagnosis of metastatic gastric or GEJ adenocarcinoma. Participants with esophageal cancer are not eligible.
- •Have not received any prior first-line systemic therapy for gastric or GEJ adenocarcinoma (prior adjuvant or neoadjuvant therapy is permitted). Participants whose disease has progressed after >24 weeks following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.
- •Have measurable or nonmeasurable but evaluable disease determined using guidelines in Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1).
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale at baseline.
- •Have adequate organ function.
- •Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator.
- •Eligible participants of reproductive potential (both sexes) must agree to use contraception (hormonal or barrier methods) during the study period and at least 6 months after the last dose of study treatment or longer if required per local regulations.
- •Are willing to provide a blood sample for research purposes. Submission of a blood sample is mandatory for participation in this study unless restricted by local regulations or ethical review boards (ERBs); submission of a tumor tissue sample is optional.
排除标准
- •Participants with human epidermal growth factor receptor 2 (HER2)-positive status as determined per local standards. Participants with a negative test or having an indeterminate result due to any reason are eligible, provided these participants are not eligible for treatment directed against tumors which overexpress HER
- •Have radiation therapy within 14 days prior to randomization. Any lesion requiring palliative radiation or which has been previously irradiated cannot be considered for response assessment.
- •Have documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
- •Have undergone major surgery within 28 days prior to randomization.
- •Are currently enrolled in, or discontinued study drug within the last 28 days from, a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants participating in surveys or observational studies are eligible to participate in this study.
- •Are pregnant or breast feeding. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of study treatment.
- •Have any prior malignancies.
- •Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the participant is, in the investigator's opinion, not an appropriate candidate for the study.
研究组 & 干预措施
S-1/Oxaliplatin + Ramucirumab
(Part A) Ramucirumab intravenously (IV) on day 1 and day 8 along with S-1 by mouth (PO) on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Ramucirumab (Drug)
S-1/Oxaliplatin + Ramucirumab
(Part A) Ramucirumab intravenously (IV) on day 1 and day 8 along with S-1 by mouth (PO) on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: S-1 (Drug)
S-1/Oxaliplatin + Ramucirumab
(Part A) Ramucirumab intravenously (IV) on day 1 and day 8 along with S-1 by mouth (PO) on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Oxaliplatin (Drug)
S-1/Oxaliplatin + Ramucirumab
(Part A) Ramucirumab intravenously (IV) on day 1 and day 8 along with S-1 by mouth (PO) on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Paclitaxel (Drug)
S-1/Oxaliplatin + Placebo
(Part A) Placebo IV on day 1 and day 8 along with S-1 PO on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Ramucirumab (Drug)
S-1/Oxaliplatin + Placebo
(Part A) Placebo IV on day 1 and day 8 along with S-1 PO on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Placebo (Drug)
S-1/Oxaliplatin + Placebo
(Part A) Placebo IV on day 1 and day 8 along with S-1 PO on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: S-1 (Drug)
S-1/Oxaliplatin + Placebo
(Part A) Placebo IV on day 1 and day 8 along with S-1 PO on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Oxaliplatin (Drug)
S-1/Oxaliplatin + Placebo
(Part A) Placebo IV on day 1 and day 8 along with S-1 PO on days 1-14 and oxaliplatin IV on day 1 of each 21 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met then move to Part B.
(Part B) Ramucirumab IV on day 1 and day 15 along with paclitaxel IV on day 1, 8, and 15 of each 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion is met.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Randomization to Radiographic Documentation of Progression or Death Due to Any Cause (Up to 25 Months)
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) or the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up were censored at the day of their last adequate tumor assessment.
次要结局
- Progression-free Survival to the Second Disease Progression (PFS 2)(Randomization to Second Radiographic Documentation of Progression or Death Due to Any Cause (Up to 31 Months))
- Overall Survival (OS)(Randomization to Death Due to Any Cause (Up to 31 Months))
- Percentage of Participants With Objective Response Rate (ORR)(Randomization to Disease Progression (Up to 25 Months))
- Disease Control Rate (DCR)(Randomization to Disease Progression (Up to 25 Months))
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A(Cycle 1 Day 1 & 8 Predose, Cycle 2 Day 1 Predose, Cycle 3 Day 1 Predose, Cycle 5 Day 1 Predose, Cycle 9 Day 1 Predose)
- Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B(Cycle 1 Day 1 predose, Cycle 2 Day 1 predose)
- Number of Participants With Anti-Ramucirumab Antibodies(Baseline through 25 months)