INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer, a Phase II Randomized Multi-center Trial With and Without APX005M, an Anti-CD40 Agonist
概览
- 阶段
- 2 期
- 干预措施
- APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days
- 疾病 / 适应症
- Locally Advanced Rectal Adenocarcinoma
- 发起方
- University of Texas Southwestern Medical Center
- 入组人数
- 58
- 试验地点
- 4
- 主要终点
- Pathological Complete Response Rate
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
Determine the complete pathologic complete response (pCR) rate in patients with locally advanced rectal adenocarcinoma.
详细描述
A phase II randomized trial 3:2 with short course radiotherapy followed by mFOLFOX chemotherapy prior to trans abdominal resection with or without an antiCD40 agonist antibody (APX005M). There will be continuous safety assessment for at least 6 patients. Planned accrual of 58 patients. An interim analysis after 30 patients have completed treatment and there will be early stopping criteria for futility or efficacy. Short course radiotherapy will consist of 5Gy x 5 to the pelvis and patients on APX005M arm will receive one infusion during radiotherapy course, have a two week break, then start FOLFOX with APX005M in conjunction with five out of six cycles of chemotherapy. Patients will be restaged and then undergo definitive surgery.
研究者
Todd Aguilera
Assistant Professor
University of Texas Southwestern Medical Center
入排标准
入选标准
- •At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
- •Willing and able to provide written informed consent
- •Pathologic diagnosis of rectal adenocarcinoma
- •Stage III or Stage II with at least 1 of the following high-risk features:
- •Distal (\<1cm from anal ring)
- •cT4 or within 3mm of MR fascia
- •Not candidate for sphincter preservation
- •Extramural venous invasion
- •No prior treatment for rectal adenocarcinoma
- •Eastern Cooperative Group (ECOG) performance status of 0-
排除标准
- •Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT or PET
- •Prior RT to the pelvis.
- •Uncontrolled comorbid illness or condition including an active infection, congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
- •Prior treatment with any 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.
- •Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating acute or chronic infection.
- •Any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
- •Malignancy in the past 3 years that required active treatment except locally curable cancers or cancers deemed by the treating physicians to not impact the subject's survival duration.
- •Participants receiving any other investigational agent, standard antineoplastic agents, or immunosuppressive agents.
- •Known history of interstitial lung disease.
研究组 & 干预措施
APX005M on day 3 of RT & day 3 of cycles 1-5 of mFOLFOX
On Day 3 of Cycles 1-5 of each mFOLFOX treatment, participants will receive another dose of APX005M. The sequence of administration of APX005M in combination with mFOLFOX. In Cycle 6, participants will receive only mFOLFOX. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study.
干预措施: APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days
Radiation Therapy 5Gy x 5 days, mFOLFOX
Participants randomized to Arm 2 will receive short-course RT and mFOLFOX regimen, except that participants will not receive any of the study drug. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study.
干预措施: mFOLFOX and Radiation Therapy 5Gy x 5 days
结局指标
主要结局
Pathological Complete Response Rate
时间窗: At time of surgery
The primary objective of this study is to determine the pathologic complete response (pCR) rate of the combined treatment modality.
次要结局
- Overall Survival(3 years)
- Toxicity analysis(3 years)
- Disease free survival(3 years)