A Phase I Study of the Bcl-XL_42-CAF09b Vaccine to Test Safety and Immunological Effect in Patients With Prostate Cancer With Lymph Node Metastases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Number and type of reported adverse events
研究概览
简要总结
In this Phase I study, patients with hormone-sensitive Prostate Cancer (PC) and lymph node metastases are treated with the cancer vaccine Bcl-xl_42-CAF09b. The aim of the study is to clarify the safety and toxicity of the vaccine and also the immunological effect.
The vaccine Bcl-xl_42-CAF09b is composed of the peptide Bcl-xl_42 and the adjuvant CAF09b. The B-cell lymphoma extra large protein (Bcl-xl) protein plays a vital role in the cancer cell's ability to avoid programmed cell death (apoptosis) and is upregulated in a variety of cancerous diseases. Bcl-xl_42 is a peptide fragment of the full protein and preclinical studies have shown that vaccination with this peptide (Bcl-xl) can activate the immune system and thereby lead to the death of cancer cells. In order to improve the activation of the immune system, adjuvant CAF09b is added; Preclinical studies have shown that special intraperitoneal (IP) injections of CAF09b improve the activation of the immune system.
详细描述
Background:
In this Phase I study, patients with hormone-sensitive Prostate Cancer (PC) and lymph node metastases are treated with the cancer vaccine Bcl-xl_42-CAF09b. The aim of the study is to clarify the safety and toxicity of the vaccine and also the immunological effect.
Patients included should be on Bicalutamid treatment upon inclusion. The vaccine Bcl-xl_42-CAF09b is composed of the peptide Bcl-xl_42 and the adjuvant CAF09b. The B-cell lymphoma extra large protein (Bcl-xl) protein plays a vital role in the cancer cell's ability to avoid programmed cell death (apoptosis) and is upregulated in a variety of cancerous diseases. Bcl-xl_42 is a peptide fragment of the full protein and preclinical studies have shown that vaccination with this peptide (Bcl-xl) can activate the immune system and thereby lead to the death of cancer cells.
In order to improve the activation of the immune system, adjuvant CAF09b is added; Preclinical studies have shown that special intraperitoneal (IP) injections of CAF09b improve the activation of the immune system.
The CAF09 adjuvant has been developed by Statens Serum Institut (SSI). It is a three-component adjuvant system, composed of cationic liposomes (DDA-MMG1) with complex bound synthetic double-stranded RNA (Poly(I:C)2). The adjuvant was developed as a means to induce cytotoxic CD8+ T-cell responses against vaccine antigens and intended for use in vaccines against disease targets such as cancers, human immunodeficiency virus or Hepatitis C virus. The Poly(I:C) component has previously been in clinical studies as a cancer treatment. Poly(I:C) is known for its pyrogenic activity but upon formulation in the cationic liposome system, CAF09, the pyrogenic effect is significantly reduced.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Not a randomized study. The first 10 patients included will be treated in arm A - the last 10 will be treated in arm B.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Histologically Verified Adenocarcinoma Prostatae
- •Diagnostic and / or histologically verified lymph node metastases
- •ECOG Performance Status ≤2
- •Primary anti-androgen treatment started
- •Adequate haematological, renal and hepatic function:
- •Neutrophil granulocytes ≥ 1.5 x 109 / l
- •Platelet counts ≥ 100 x 109 / l
- •hemoglobin ≥ 5.6 mmol / l
- •Serum creatinine ≤ 1.5 times upper normal limit
- •AST or ALAT ≤ 2.5 times upper normal limit
- •serum bilirubin ≤ 1.5 times upper normal limit
- •Alkaline phosphatase ≤ 2.5 times upper normal limit
- •INR <1.5 / PP <40
排除标准
- •Verified bone or visceral metastases
- •Serious allergy or previous anaphylactic reactions
- •Known hypersensitivity to any of the active substances or to any of the excipients.
- •Other malignant disease within the last three years, rendering planocellular and basocellular skin carcinoma
- •Known infection with HIV, hepatitis B and C virus, regardless of whether the infection is kept calm with medical treatment
- •Severe medical disorder, severe asthma, severe COPD, poorly regulated cardiovascular disease or diabetes
- •Active autoimmune disease, e.g. autoimmune neutropenia / thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, goodpasture syndrome, Addison's disease, Hashimoto's thyroiditis, active grave disease, morbus chrohn or ulcerative colitis
- •Major gastrointestinal surgical procedures within the last 3 months
- •Previous treatment with other cancer vaccine
- •Concomitant immunosuppressive treatment including prednisolone and methotrexate
- •Ongoing anticoagulant treatment (treatment with acetylsalicylic acid and clopidogrel is allowed)
- •Psychiatric disease which, according to the investigator's discretion, may affect compliance
- •Co-administration with other experimental drugs.
结局指标
主要结局
Number and type of reported adverse events
时间窗: 0-30 weeks
Determine the safety of the Bcl-XL\_42-CAF09b vaccine for patients with prostate cancer with lymph node involvement who are on Bicalutamid treatment by reporting adverse events according to CTCAE v. 4.0
次要结局
- Treatment related immune responses(Up to 24 months)