A Phase I Open-label Study to Evaluate Safety and Immunologic Response of COMBIG-DC Administered Intra-tumorally in Patients With Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Registration of adverse events as a measure of safety and tolerability
研究概览
简要总结
The primary objective of this study is to answer the question "Is it possible to inject the COMBIG-DC vaccine in a hepatic tumor without getting unacceptable side effects"?
详细描述
Patients diagnosed with hepatocellular carcinoma will get COMBIG-DC vaccinations at three occasions with 2-3 weeks and 3-5 weeks between vaccination 2 and 3 respectively. Adverse events will be registered until 6 months after last vaccination, as well as changes in vital signs (heart rate, blood pressure and body temperature) and lab parameters. Immunologic response will be evaluated by measuring immunologic markers in blood. The size of the tumor/tumors will be evaluated after 3 and 6 months and thereafter every three months until tumor progression.
For patients included after approval of Amendment 3 (2015-12-10), COMBIG-DC will be given as add on to standard treatment; sorafenib or Transarterial Chemoembolization (TACE).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be informed of the nature of the study and have provided written informed consent
- •At least 18 years of age.
- •Diagnosis of hepatocellular carcinoma according to EASL criteria or pathology.
- •Radiologically measurable liver tumor(s), i.e. at least 20 mm in longest uni-dimensional diameter as measured by CT/MRI
- •Not eligible for curatively aiming treatment or TACE. Tumor stage B or C according to BCLC.
- •For patients included according to Amendment 3: tumour stage A, B or C according to BCLC and
- •eligible for sorafenib treatment or having ongoing sorafenib treatment for not more than 4 weeks ant the time for inclusion or
- •eligible for TACE or having received not more than 1 previous TACE treatment.
排除标准
- •Performance status > ECOG 2
- •Liver function according to Child-Pugh >7 points.
- •Known major reaction/adverse event in connection with previously made vaccination (e.g. asthma, anaphylaxia or other serious reaction).
- •Known major reaction/adverse event in connection with previous transfusions of blood products
- •Active autoimmune disease requiring treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases.
- •Tested positive for HIV
- •Active disease (HBV and HCV) requiring antiviral treatment
- •Ongoing infection that requires treatment with antibiotics or antiviral medication
- •Treatment with immunosuppressive treatments like corticosteroids (Immunosuppression (within 28 days) prior to the first injection of COMBIG-DC. Inhaled, intranasal and local steroids accepted), or mTor inhibitors within 28 days before first vaccination.
- •Patients with prior history of malignancy other than HCC, within the preceding 3 years OR with relaps after complete response, except for 5 years follow-up of adequately treated in situ carcinoma without recurrences or non-melanoma skin cancer.
- •Inadequate laboratory parameters, i.e.:
- •P-Prothrombincomplex (PK) >1.4,
- •Platelet count <50 75 x109/L
- •Leukocyte count <3.0 x 109/L
- •P-APT time outside normal limit
- •Previous organ transplantation
- •Women of Childbearing Potential (WOCBP) refusing to use adequate contraception (oral or injectable contraceptives, hormone releasing intrauterine device) throughout the study period.
- •Pregnant or lactating women
- •Life expectancy less than 3 months.
- •Concomitant anti-tumor treatment (within 28 days) prior to the first injection of COMBIG-DC, except for sorafenib or TACE for patients included according to Amendment
- •For patients included according to Amendment 3: Previous systemic anti-cancer treatment.
- •Investigational treatment (within 28 days) prior to the first injection of COMBIG-DC.
- •Known blood dyscrasia (bleeding complication).
- •Known malignancy in CNS
- •Any reason that, in the opinion of the investigator, contraindicates that the patient participates in the study.
研究组 & 干预措施
COMBIG-DC
COMBIG-DC (allogeneic dendritic cells) Cancer Vaccine 3 vaccinations: 5, 10 or 20 million cells per injection
干预措施: COMBIG-DC (ilixadencel) (Biological)
结局指标
主要结局
Registration of adverse events as a measure of safety and tolerability
时间窗: Up to 6 months after last patient's last vaccination
* Changes in vital signs from baseline (heart rate, blood pressure, body temperature) * Changes in lab parameters from baseline * Short term worsening in ECOG and/or Child Pugh and/or MELD score * Local procedural injuries, assessed by MRI or ultrasound
次要结局
- Change in body weight(3 and 6 months after last vaccination)
- To evaluate systemic immunological response(Up to 3 months after last vaccination)
- To evaluate systemic inflammatory response(Until 3 months after last vaccination)
- Long term changes in ECOG scores(3 and 6 months after last vaccination)
- To study overall survival (OS)(Up to 6 months after last patient's last vaccination)
- To evaluate tumor control(Until 6 months after last patient's last vaccination)
- Long term changes in Quality of Life scores(3 and 6 months after last vaccination)
- To evaluate immunological response(Up to 3 months after last vaccination)
- Changes in HBV, HCV virus titers(Day 8 after each injection and at the 3 and 6 months visit)
- To study time to progress (TTP)(Measured every 3 months until progression)