Evaluation of p53peptide-pulsed Dendritic Cells in Combination With an Aromatase Inhibitor as a Treatment for Patients With Breast Cancer With Disease Recurrence After Adjuvant or First Line Endocrine Therapy.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- To determine time to progression
研究概览
简要总结
The primary aim of this study is to investigate time to progression in breast cancer patients vaccinated with autologous dendritic cells pulsed with peptides in combination with adjuvant aromatase inhibitor (AI), Thymosin 1 alpha and interleukin-2. The secondary aim is to investigate whether a measurable immune response can be induced, and to evaluate the clinical effect (objective response rate) of the vaccination regime.
详细描述
Only patients who have tumors > 5 % positive for p53 by IHC can be referred to this treatment. All patients will receive standard dosage of AI +/- p53-DC vaccination. Patients who express HLA-A2 will also receive DC vaccination. Patients that do not express HLA-A2 will receive only AI and be regarded as controls.
The vaccination regime consists of primary 10 intradermal injections of 1-2 weeks interval (q1w x 4 → q2w x 6) with p53 peptide-pulsed dendritic cells, followed by monthly injections until progression; proleukin and Zadaxin are used as vaccine adjuvants.
Defined procedures are employed for generation of autologous dendritic cells for clinical application in a classified laboratory. Unmobilized leukapheresis will be used for isolation of large-scale mononuclear cells, and dendritic cells will be generated from monocytes by cytokine stimulation and loaded with p53 peptides. Frozen preparations of dendritic cells will be prepared using automated cryopreservation.Each patient will receive a minimum of 5x10^6 dendritic cells per treatment supplemented with interleukin-2 6 MIU/m² sc per vaccine and 1.6 mg Thymosin 1 alpha sc x 2/week.
Toxicity including autoimmunity will be evaluated using the common Toxicity Criteria (CTC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with histological proven metastatic or locally advanced ER+/PGR+ breast cancer in progression after receiving
- •line endocrine therapy.
- •Further inclusion criteria: p53+ tumour, PS≤1, postmenopausal. Age >18, PS ≤ 1 and acceptable CBC and blood chemistry results
排除标准
- •Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinoma in situ of the cervix and basal/squamous carcinoma of the skin)
- •Patients with metastatic disease in the central nervous system
- •Patients with other significant illness including severe allergy, asthma, DM, angina pectoris or congestive heart failure
- •Patients with acute or chronic infection including HIV, hepatitis og TB
- •Patients who received antineoplastic therapy including chemotherapy, radiation, immunotherapy or other agents, less than 4 weeks before the beginning of the trial
- •Patients who received corticosteroids or other immunosuppressive agents
- •Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis
- •Severe hypercalcemia
研究组 & 干预措施
Aromatase inhibitor and DC vaccination
the HLA-A2 positive patients will be treated with AI, DC vaccines, Zadaxin and IL-2
干预措施: DC vaccine (Biological)
Aromatase inhibitor
the HLA-A2 negative patients will receive AI only
干预措施: DC vaccine (Biological)
Aromatase inhibitor
the HLA-A2 negative patients will receive AI only
干预措施: aromatase inhibitor (Drug)
结局指标
主要结局
To determine time to progression
时间窗: after 8 and 16 weeks
次要结局
- To evaluate safety of DC vaccination in combination with AI, to evaluate clinical tumor response, to evaluate treatment induced immune response to p53 end to evaluate duration of tumor and immune responses(Weekly the first 4 weeks, thereafter biweekly for five months, thereafter monthly)
研究者
Inge Marie Svane
Prof, MD, PhD
Herlev Hospital