Immunogenicity and Safety of Autologous Dendritic Cells in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy.
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
- Adverse effects
研究概览
简要总结
This study aims to evaluate for the first time in Colombia the immunogenicity and safety of autologous DCs as enhancers of the immune response in patients with ductal breast cancer who, prior to surgical resection of the tumor, will receive neo-adjuvant chemotherapy with Doxorubicin and Cyclophosphamide. concomitantly with the transfer of autologous DCs. This clinical trial is based on the concept proposed in countries like France more than a decade ago, that chemotherapy or radiotherapy cause the tumor cells to release certain signals that favor the activation of the immune system against cancer. Therefore, the combined use of chemotherapy with vaccination with dendritic cells would provide the immune system with greater antitumor response capacity, taking advantage of the release of said signals to initiate a series of processes that would be reflected in the activation of T lymphocytes capable of destroying the remaining cells of the tumor. To determine the specificity of the response evoked by the adoptive transfer of autologous DCs, in each patient the degree of recognition of the tumor by the immune system before and after said procedure will be evaluated. These results will be compared with those of patients who participated in a control group.
Hypothesis Adoptive transfer of autologous DCs generated in vitro, in patients with stage IIA-IV breast cancer who receive neoadjuvant therapy with Doxorubicin and Cyclophosphamide, is a safe procedure that stimulates anti-tumor immune responses in treated patients.
Principal aim:
To evaluate the safety and immunogenicity of the use of DCs when used in patients with stage IIA-IV breast cancer in association with neo-adjuvant chemotherapy with Doxorubicin/Cyclophosphamide.
Specific aims:
- Generate immuno-competent dendritic cells in conditions of Good Clinical Practice and Good Laboratory Practices.
- Determine in each patient the immunological status of specific T lymphocytes against tumor antigens, before and after chemotherapy, in order to demonstrate whether the adoptive transfer of DCs favors the anti-tumor immune response.
- Register in patients with breast cancer in neo-adjuvant chemotherapy the class and frequency of adverse effects that could be generated as a result of the adoptive transfer of autologous DCs.
详细描述
The Fundación Salud de los Andes in the framework of a strategic alliance with the National University of Colombia has been working in the planning and development of a clinical trial in Colombia that promotes the search for new therapeutic alternatives for cancer patients. As a translational medicine project, it aims to make the laboratory findings available to the patient. This study explores the combination of immunotherapy (cell therapy) with chemotherapy, in order to obtain better results in the therapeutic management of tumors in patients with breast cancer.
Problem:
Breast cancer is a pathology that in recent years has increased vertiginously its incidence globally. Given the advanced state in which this tumor is usually diagnosed in our environment, the prognosis is seriously compromised, which has led to the current breast cancer represents a major public health problem in Colombia. The established therapies for the management of patients with this type of tumors such as chemotherapy, radio-therapy or surgery, are effective to reduce much of the established tumor mass, but fail to eliminate residual cancer cells, so - often - these treatments cannot prevent the recurrence of the disease. In addition to the above, the quality of life of the patients treated is strongly affected by the toxicity of these treatments on healthy tissues and their undesirable effects, which frequently affects poor adherence to treatment. That is why it is necessary to search for new therapeutic alternatives that are more specific to the tumor and that are better tolerated by patients. Due to the high specificity of the immune system for the recognition of tumors, different modalities of immune therapy for tumor control are currently being explored, which seek to enhance the performance of the patient's defense system so that a cytotoxic and memory response is established against them. tumor cells.
Type of study Clinical Trial Phase I / II.
Methodology:
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
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women between 30 and 65 years old.
- •Patients who have histologically confirmed primary invasive ductal carcinoma of the breast.
- •Patients who, at the time of their evaluation, present a breast cancer with TNM classification: IIA, IIB, IIIA, IIIB, IIIC or IV; in whom the breast-tumor relationship is not satisfactory for the surgical procedure, so that they will receive neo-adjuvant chemotherapy with Doxorubicin and Cyclophosphamide for at least 3 cycles.
- •Patients who voluntarily agree to enter the proposed immunotherapy scheme.
- •Absence of second malignant disease with the exception of a cervical carcinoma or a treated basal cell carcinoma.
- •Normal blood, kidney function and hepatic function (neutrophil count 1000 / mm3, lymphocyte count 500 / mm3, hemoglobin 8mg / dl, and platelet count 150,000 / mm3, serum creatinine 1.5mg / dl, BUN 50mg / dl, aminotransferases 2 times of normal value and bilirubin 2.0mg / dl).
- •Karnofsky higher than 70% or ECOG 0 to
- •Life expectancy greater than three months.
- •Ability to understand informed consent.
- •Have a weight greater than 50 Kilos at the time of apheresis.
排除标准
- •Patients who are pregnant or breast-feeding.
- •Patients who have received some type of therapy as treatment for their tumor pathology in the breast, prior to the start of the trial (radiotherapy, chemotherapy, immunotherapy or gene therapy).
- •Metastasis to the central nervous system at the time of inclusion in the study.
- •Active autoimmune disease requiring treatment or history of autoimmune disease, which could be exacerbated by treatment. Patients with endocrine disease controlled by replacement therapy may be included, including thyroid disease, adrenal disease and vitiligo.
- •Presence of a chronic or acute infection, such as HIV, viral hepatitis or tuberculosis, before or after the signing of the informed consent.
- •Use of immunosuppressant within 4 weeks prior to the trial (eg corticosteroids), such as azathioprine, prednisone or cyclosporine A. The use of local steroids (topical, nasal or inhaled) may be acceptable.
- •Patients with eczema, history of eczema or other eczematous skin disorders or those with acute or chronic exfoliative skin condition (eg atopic dermatitis, burns, impetigo, varicella zoster, severe acne or open wounds).
- •Any disease that could interfere with the patient's ability to carry out the treatment (eg, Crohn's disease, ulcerative colitis or active diverticulitis, severe respiratory, cardiovascular, neurological, infectious disease or uncontrolled metabolic disease), including diseases of the psychiatric type.
- •Clinically significant cardiomyopathy, which requires treatment.
- •Splenectomized patients.
- •Patients who do not receive the neo-adjuvant chemotherapy regimen with Doxorubicin and Cyclophosphamide for three cycles.
- •Patients who have had an excisional biopsy.
研究组 & 干预措施
Vaccinated
Transfer of autologous dendritic cells interspersed with chemotherapy doses
干预措施: Dendritic cells (Biological)
Control
Control patients who follow their basic treatment with chemotherapy with the A/C scheme
结局指标
主要结局
Adverse effects
时间窗: One year after innoculation
Number of participants with treatment-related adverse events as associated with DCs inoculation assessed by CTCAE v4.0
次要结局
未报告次要终点