Study to Nivolumab Following Preoperative Chemoradiotherapy
A Phase 1b/2 Multicenter Study to Investigate the Safety, Efficacy and Proof of Concept (POC) of Nivolumab Monotherapy as a Sequential Therapy Following Preoperative Chemoradiotherapy Patients With Locally Advanced Resectable Rectal Cancer
研究概览
详细说明
[Phase Ib]
After preoperative CRT, to sequentially administer nivolumab in combination for patients with locally advanced resectable rectal cancer. To evaluate the safety of nivolumab in sequential combination therapy, the onset of dose-limiting toxicity (DLT) and the safety of subsequent surgical therapy, and to decide on a recommended dose (RD) for the phase II part.
[Phase II] PhaseⅡ is composed of 4 cohorts.
Cohort A: First-onset rectal cancer cohort (42 cases) To evaluate the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered following preoperative CRT.
And to search for biomarkers related to therapeutic effects in first-onset cases. Evaluate the safety of surgical treatment.
Cohort B: Rectal cancer with localized recurrence cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.
Search for biomarkers related to therapeutic effects in localized recurrence cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Cohort C: Rectal cancer with resectable lung/liver metastasis cohort (10 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (at the RD determined in Phase Ib) in sequential combination with surgery, administered after preoperative CRT.
Search for biomarkers related to therapeutic effects in resectable lung/liver metastasis cases. Conduct an exploratory evaluation on the safety of surgical treatment.
Cohort D: First-onset rectal cancer using ipilimumab-nivolumab combination cohort (25 cases) To conduct an exploratory evaluation of the efficacy and safety of nivolumab (240 mg/body at two-week intervals) and ipilimumab (1 mg/kg at six-week intervals) after preoperative CRT, and search for biomarkers related to therapeutic effects in first-onset cases. Conduct an exploratory evaluation on the safety of surgical treatment.
研究类型
注册 (预期的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名:Hideaki Bando, Dr
- 电话号码:+81-52-762-6111
- 邮箱:voltage_core@east.ncc.go.jp
研究联系人备份
- 姓名:Yuichiro Tsukada, Dr
- 电话号码:92331 +81-4-7133-1111
- 邮箱:voltage_core@east.ncc.go.jp
学习地点
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Osaka、日本
- 招聘中
- Osaka National Hospital
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Chiba
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Kashiwa、Chiba、日本
- 招聘中
- National Cancer Center Hospital East
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Hokkaido
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Sapporo、Hokkaido、日本
- 招聘中
- Hokkaido University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion criteria:
(A. Phase Ib and Cohorts A and D only)
A1. Rectal cancer patients who have not undergone treatment for pre-CRT tumors situated 12 cm or less from the lower edge of the AV.
A2. The primary rectal lesion is histopathologically diagnosed as adenocarcinoma.
A3. Pre-CRT clinical stage is clinical T3-4 N-any M0.
A4. Macroscopic radical resection is deemed possible on pre-CRT image diagnosis.
A5. Aged between 20 and 80 years at the time of enrollment.
(B. Cohort B only)
B1. Clinically diagnosed with local recurrence after rectal surgery.
B2. The main site of recurrence is limited to the pelvis by pre-CRT imaging diagnosis.
B3. Macroscopic radical resection is deemed possible on pre-CRT imaging diagnosis.
B4. Aged between 20 and 75 years at the time of enrollment.
(C. Cohort C only)
C1. Rectal cancer patients who have not undergone pretreatment for a pre-CRT tumor which is 12 cm or less from the lower AV.
C2. The primary rectal lesion is histopathologically diagnosed as adenocarcinoma.
C3. The pre-CRT clinical stage is clinical T3-4 N-any M1a (liver) M1a (lungs).
C4. Macroscopic curative resection of the primary rectal lesion is deemed possible on pre-CRT imaging diagnosis.
C5. A metastatic liver tumor or a metastatic lung tumor has been diagnosed as clinically resectable prior to CRT and during clinical trial enrollment.
(D. Common to all cohorts in Phase Ib and Phase II)
D1. Patients who have provided consent through a consent form.
D2. Patients whose Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is 0 or 1 at the time of enrollment.
D3. CRT was administered:
D4. Patients whose CRT adverse events have recovered to Grade 1 or lower based on CTCAE ver.4.0. within 14 days after the end of CRT, and are expected to be able to take nivolumab (patient is still eligible even if adverse events are not restored to Grade 1, provided that the blood cell count satisfies the eligibility criteria specified in point D8).
D5. Patients with no remote metastases as confirmed by imaging at the end of CRT (testing is allowed from 14 days before the end of CRT to the trial enrollment date).
D6. For women who may become pregnant (including patients who are not menstruating due to chemically-induced menopause among other medical reasons), patients who agree to use contraception for at least 23 weeks after the last administration of the investigational drug, starting from the day they provide consent (30 days (ovulation cycle) plus five times the elimination half-life of the investigational drug).
D7. For men, patients who agree to use contraception for at least 31 weeks after the last administration of the investigational drug, starting from the day they provide consent (90 days (spermatogenesis cycle) plus five times the elimination half-life of the investigational drug).
D8. Patients who have the sufficient organ function at the time of enrollment.
Exclusion criteria
Patients diagnosed with active double cancer (synchronous double cancer and double cancer with disease-free period within five years from enrollment).
However, lesions equivalent to intraepithelial or mucosal carcinoma deemed cured by localized treatment are not classified as active double cancer.
- Patients with a history of pelvic irradiation prior to this rectal cancer treatment.
- Patients who have not given consent through the informed consent form.
- Patients deemed by the investigator to be ineligible for the trial.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Nivolumab & Ipilimumab(Only Cohort D)
chemoradiotherapy with capecitabine+ Nivolumab + Ipilimumab(Only Cohort D) + surgical therapy
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Capecitabine:Dose of 1650mg/m2,14days, Radiation:45Gy/25 fractions, Nivolumab :240mg on day1 of each cycle, Surgical therapy:The resection (LAR), intersphincteric resection (ISR), or abdominoperineal resection (APR).
其他名称:
For only Cohort D,1 mg/kg at six-week intervals
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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病理完全缓解
大体时间:1年
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将使用美国癌症联合委员会 (AJCC) 癌症分期评估病理学完全缓解
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1年
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Objective response rate
大体时间:1 year
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Evaluation Criteria In Solid Tumors (RECIST)
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1 year
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Recurrence pattern (local or distant)
大体时间:1 year
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1 year
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Disease-free survival (DFS)
大体时间:5years
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Evaluation Criteria In Solid Tumors (RECIST)
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5years
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Overall survival (OS)
大体时间:5years
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Evaluation Criteria In Solid Tumors (RECIST)
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5years
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Incidence of adverse events (AEs)
大体时间:1 year
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Safety will be evaluated with CTCAE v4.0
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1 year
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Rate of completing the protocol therapy
大体时间:1 year
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1 year
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Rate of radical resection
大体时间:1 year
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1 year
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Safety evaluation
大体时间:5years
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Safety will be evaluated with CTCAE v4.0
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5years
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macroscopic evaluation of (rectal cancer) resected specimen
大体时间:1 year
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1 year
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合作者和调查者
调查人员
- 学习椅:Takayuki Yoshino, Dr、Gastrointestinal Oncology Division National Cancer Center Hospital East
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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