Chemo-Immunotherapy, Gemcitabine With Pegylated Interferon Alpha-2b (Peg-Intron) With and Without p53 Synthetic Long Peptide (p53 SLP) Vaccine, for Patients With Platinum Resistant Ovarian Cancer CHIP Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination
研究概览
简要总结
This study investigates the feasibility and immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination in patients with platinum-resistant ovarian cancer.
详细描述
Recurrent ovarian cancer has a dismal prognosis and there is a pressing need to identify more efficient therapies. Ovarian cancer is highly immunogenic and good survival is tightly linked to the presence of tumor-infiltrating T cells and the absence of immunosuppressive immune cells. This anti-tumor immune response might be primed by chemotherapy.
Gemcitabine has immune-modulatory properties in addition to its direct cytotoxic effect in platinum resistant ovarian cancer. Additionally, Peg-Intron allows the full maturation of dendritic cells, thereby enhancing the anti-tumor response. Moreover, the tumor-associated self-antigen p53 is commonly over-expressed in ovarian cancer and can serve as a target for immunotherapy. Therefore, chemo-immunotherapy with gemcitabine and Peg-Intron plus/minus p53 SLP vaccination seems an attractive treatment for recurrent, p53+ ovarian cancer patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histological proven epithelial ovarian cancer, peritoneal cavity or fallopian tube cancer (inclusive mucinous or clear cell tumors)
- •Tumor over-expressing p53
- •Progression of disease or relapse after previous therapy with platinum
- •Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper limit of normal within 3 months and confirmed
- •Age ≥ 18 years
- •WHO performance status 0-2
- •Adequate bone marrow function: WBC ≥ 3.0 x 109/l, neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l
- •Adequate liver function: bilirubin ≤ 1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤ 2.5 x UNL, Alkaline Phosphatase ≤5 x UNL
- •Adequate renal function: the calculated creatinine clearance should be ≥ 50 mL/min
- •Survival expectation > 3 months
- •Patients must be accessible for treatment and follow-up
- •Written informed consent according to the local Ethics Committee requirements
排除标准
- •Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
- •Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
- •Known hypersensitivity reaction to any of the components of the treatment
- •Pregnancy or lactating
- •Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
研究组 & 干预措施
Group 2
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron)
干预措施: Interferon Alfa-2b (Drug)
Group 3
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin
干预措施: Interferon Alfa-2b (Drug)
Group 3
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin
干预措施: p53 SLP (Biological)
结局指标
主要结局
Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination
时间窗: Before treatment, after 2 months and after 6 months after start therapy
During the trial we will measure the incidence and severity of all side effects (according to CTC version 4.0). The change in immunogenecity will be measured according to the induction of p53-specific T cells upon treatment.
次要结局
- progression free survival(Before treatment, after 2 months and after 6 months after start therapy)
- overall survival(Before treatment, after 2 months and after 6 months after start therapy)
- Clinical outcome (response (RECIST 1.1)(Before treatment, after 2 months and after 6 months after start therapy)
- The effect of this new treatment combination on the immune system(Before treatment, after two months and after 6 months after treatment)
研究者
J.R. Kroep
MD phD
Leiden University Medical Center