Phase II Trial to Evaluate the Addition of Nivolumab to Neoadjuvant Chemoradiation With FOLFOX for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- pathological complete response (pCR) rate
研究概览
简要总结
This is a phase II, prospective, open label, one-center study for evaluation of the addition of nivolumab to the chemotherapy phase of the neoadjuvant treatment for locally advanced rectal cancer patients. Subjects must have received no prior treatment for rectal cancer (chemotherapy, radiotherapy or surgery) and no prior treatment with checkpoint inhibitors.
Eligible subjects will receive chemoradiation for a period of 5 weeks, 6 cycles of chemo-immunotherapy (mFOLFOX6 + nivolumab) for a period of 12 weeks, once every 2 weeks, and will undergo surgery after 4 weeks.
Patients with cCR will be offered the alternative strategy of WW. Post-study systemic treatment, up to 4 cycles of mFOLFOX6, will be left to the discretion of the treating physician. This will be started 4-8 weeks post-operatively, or immediately after the demonstration of cCR in patients determined to undergo WW.
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
- •Signed written IRB approved informed consent
- •Age ≥ 18 years
- •ECOG PS 0-1
- •Subjects with histologically confirmed primary (non-recurrent) locally advanced rectal adenocarcinoma
- •Stage T3-4 N0 or TX N+ according to baseline rectal EUS and PET-CT
- •Patients who are planned for neoadjuvant chemoradiation and are surgical candidates
- •No prior chemotherapy, radiotherapy or surgery for rectal cancer
- •No prior radiotherapy to the pelvis, for any reason
- •Presence of adequate contraception in fertile patients
- •Women of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug
- •Women must not be breastfeeding
- •Ability to swallow tablets
- •No previous (within the last 5 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin
排除标准
- •Active autoimmune disease. [Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll]
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- •Pregnancy or breastfeeding
研究组 & 干预措施
Neoadjuvant Treatment
All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment
干预措施: Capecitabine (Drug)
Neoadjuvant Treatment
All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment
干预措施: Radiation therapy (Radiation)
Neoadjuvant Treatment
All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment
干预措施: mFOLFOX6 (Drug)
Neoadjuvant Treatment
All subjects will receive chemoradiation followed by chemotherapy and nivolumab as neoadjuvant treatment
干预措施: Nivolumab (Drug)
结局指标
主要结局
pathological complete response (pCR) rate
时间窗: Time from start of neoadjuvant treatment until surgical resection, assessed up to 24 months
pCR is defined when no tumor is found on pathology review of the surgical specimen (TRG -0)
Incidence of Treatment-Emergent Adverse Events (Safety)
时间窗: Time from screening until the end of study drug administration, assessed up to 24 months
Treatment-emergent AEs will be graded according to NCI CTCAE v4.0, vital signs and clinical laboratory
modified pathological complete response
时间窗: Time from start of neoadjuvant treatment until surgical resection in operated patients (pCR) and long-term (≥12 months) clinical complete response (cCR) in unoperated patients, assessed up to 24 months.
We defined a novel primary endpoint, combining pathological complete response (pCR) rate among operated patients and long-term (≥12 months) clinical complete response (cCR) rate for those electing watchful waiting, into a composite endpoint of modified pCR (mpCR) rate.
次要结局
- Disease Free Survival (DFS)(Time from the first day of treatment to the first event of: loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death from any cause, assessed up to 42 months)
- Overall Survival (OS)(The time interval between the first day of treatment and the date of death of any cause, assessed up to 66 months)
研究者
Baruch Brenner
Head, Department of Oncology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital
Rabin Medical Center