A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Recurrence free survival (RFS)
研究概览
简要总结
Background:
Gastrointestinal (GI) cancer affects the organs (such as the stomach, large and small intestine, pancreas, colon, liver, and biliary system) of the digestive tract. In some participants who have had surgery for GI cancer, blood tests show that the cancer has spread despite being unable to be identified by scans. Certain gene mutations (changes) in GI cancer (such as KRAS or TP53) can be targeted by T cells, a type of immune cell, in individuals with specific HLA types (genes that help proteins in the body know what is self and non-self). Researchers want to see if they can stop GI cancer from returning or spreading in people with these gene mutations and specific HLA types.
Objective:
To test therapy with modified T-cells to prevent or delay the return of GI cancer after standard treatment. T-cells play a role in the body s immune system.
Eligibility:
People aged 18 to 72 years with GI cancer that was treated with standard therapy and is not seen on imaging scans. They must have specific gene mutations and HLA types. They also must have certain clinical or blood tests showing the cancer is spreading (elevating CA19-9 or detectable ctDNA).
Design:
Participants will be divided into 2 groups. Participants nor the study team can choose what Group to participate in; this is done by randomization , like flipping a coin. Participants will have a 1-to-1 chance of being in Group 1 or Group 2.
Group 1 will receive T-cell therapy. Their own T-cells will be collected. In a lab, the cells will be combined with a virus that carries a protein to target cancer cells.
Group 1 participants will stay in the hospital for 3 weeks or more. They will have chemotherapy, and their modified T-cells will be infused through a tube attached to a needle inserted into a vein.
Group 1 participants will visit the clinic every 3 months for 1 year and then every 6 months for 5 years. Then they will have follow-up visits for another 10 years under a different protocol.
Group 2 participants will not receive treatment with T-cells. They will visit the clinic every 3 months for 1 year and then every 6 months for 5 years.
详细描述
Background:
-Despite definitive surgical resection and (neo)adjuvant chemotherapy, many patients with gastrointestinal carcinomas (GIC) remain at high risk of recurrence and disease-specific mortality. This includes virtually all patients with resected pancreas ductal adenocarcinoma
(PDAC), patients with resected colorectal liver, lung, and/or lymph node metastases (CRLM) with persistently elevated circulating tumor DNA (ctDNA) after resection, and patients with localized GIC (other than PDAC) with persistently elevated ctDNA after resection (GIC). These patients need systemic therapies that can prevent recurrence by eradicating occult micrometastatic disease.
-We have safely treated patients with metastatic GIC using adoptive cell transfer (ACT) autologous tumor-infiltrating lymphocytes (TIL) and with peripheral blood lymphocytes transduced with a T-cell receptor (TCR) specific for a shared hot-spot mutation in KRAS
or TP53 (TCR T-cell therapy). We have demonstrated that TIL can mediate long-term responses in patients with metastatic GIC, providing proof of concept that cell transfer can be effective in low tumor mutational burden, microsatellite stable epithelial cancers, and
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
- None
入排标准
- 年龄范围
- 18 Years 至 72 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1/ TCR T-cells and aldesleukin
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + TCR T cells + aldesleukin
干预措施: KRAS TCR-Transduced PBL (Biological)
1/ TCR T-cells and aldesleukin
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + TCR T cells + aldesleukin
干预措施: Aldesleukin (Drug)
1/ TCR T-cells and aldesleukin
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + TCR T cells + aldesleukin
干预措施: Fludarabine (Drug)
1/ TCR T-cells and aldesleukin
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + TCR T cells + aldesleukin
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Recurrence free survival (RFS)
时间窗: 12 weeks then every 3 months x 3, every 6 months after that until progression or 5 years since randomization.
RFS will be assessed with tumor markers and radiographic findings in each group and reported using the Kaplan-Meier method with 95% confidence intervals on the median RFS in each group.
次要结局
- Overall survival (OS)(12 weeks then every 3 months x 3, every 6 months after that until progression or 5 years since randomization. After progression contact with participants every 6 months until the first of death or 5 years after randomization.)
- Safety(until 6 months after the last dose of study agents)