T-cell Therapy in Combination With Checkpoint Inhibitors for Patients With Advanced Ovarian-, Fallopian Tube- and Primary Peritoneal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Participants With Reported Adverse Events by Type
研究概览
简要总结
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.
详细描述
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with ACT with TILs in combination with checkpoint inhibitors.
To evaluate treatment related immune responses To evaluate clinical efficacy
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological proven advanced ovarian-, fallopian tube or primary peritoneal cancer with the possibility of surgical removal of tumor tissue of > 1 cm
- •Progressive or recurrent resistant disease after platin-based chemotherapy (platinum resistant) or progressive or recurrent disease after second line or additional chemotherapy.
- •Age: 18 - 70 years.
- •ECOG performance status of ≤1 (Appendix 2).
- •Life expectancy of > 6 months.
- •At least one measurable parameter in accordance with RECIST 1.1 -criteria's.
- •No significant toxicities or side effects from previous treatments, except sensoric- and motoric neuropathy and/or alopecia
- •Sufficient renal, hepatic and hematological function
- •Men and women in the fertile age must use effective contraception. This applies from inclusion and until 6 months after treatment.
- •Able to comprehend the information given and willing to sign informed consent
排除标准
- •Other malignancies, unless followed for ≥ 5 years with no sign of disease
- •Known hypersensitivity to one of the active drugs or one or more of the excipients.
- •Severe medical or psychiatric conditions
- •Creatinine clearance < 70 ml/min. In selected cases it can be decided to include a patient with a GFR < 70 ml/min with the use of a reduced dose of chemotherapy.
- •Acute/chronic infection with HIV, hepatitis, syphilis among others.
- •Severe allergies or previous anaphylactic reactions.
- •Active autoimmune disease
- •Pregnant women and women breastfeeding.
- •Need for immunosuppressive treatment e.g. corticosteroids or methotrexate. In selected cases a systemic dose of ≤10 mg prednisolone or a transient planned treatment that can be stopped before TIL therapy can be tolerated.
- •Simultaneous treatment with other experimental drugs.
- •Simultaneous treatment with other systemic anti-cancer treatments.
- •Patients with active and uncontrollable hypercalcaemia.
研究组 & 干预措施
Patient group
All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.
干预措施: Cyclophosphamide (Drug)
Patient group
All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.
干预措施: Fludarabine (Drug)
Patient group
All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.
干预措施: TIL infusion (Biological)
Patient group
All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.
干预措施: Interleukin-2 (Drug)
Patient group
All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.
干预措施: Ipilimumab (Drug)
Patient group
All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of Participants With Reported Adverse Events by Type
时间窗: Up to 12 months
Determine the safety of TIL therapy in combination with checkpoint inhibitors for patients with ovarian-, fallopian tube or primary peritoneal cancer by reporting adverse events according to CTCAE v. 4.0.
次要结局
- Objective Response Rate(Assessed up to 12 months after therapy.)
- Treatment Related Immune Responses(Until protocol end, until 6 months after TIL infusion)
- Overall Survival(Up to 3 years after TIL infusion)
- Progression Free Survival(Up to 12 months after TIL infusion)
研究者
Inge Marie Svane
M.D., Professor
Herlev Hospital