A Non-controlled, Single Arm, Open Label, Phase II Study of Intravenous and Intratumoral Administration of ParvOryx in Patients With Metastatic, Inoperable Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Shedding of viral genomes [Vg]
研究概览
简要总结
Investigation on safety, tolerability and efficacy of parvovirus H-1 (ParvOryx) in subjects suffering from metastatic, inoperable pancreatic cancer with at least one hepatic metastasis.
详细描述
Investigation on safety, tolerability and efficacy of parvovirus H-1 (ParvOryx) in subjects suffering from metastatic, inoperable pancreatic cancer with at least one hepatic metastasis.
Initially four equal doses of ParvOryx will be administered intravenously on four consecutive days. Seven to fourteen days after the first intravenous administration the drug will be injected directly in a hepatic metastasis of the pancreatic cancer.
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
- •Age at least 18 year,
- •Ability to give informed consent,
- •Histologically confirmed pancreatic ductal adenocarcinoma (PAD) with at least one measurable hepatic metastasis according to RECIST 1.1,
- •Disease progression despite first line therapy (whatever chemotherapy regimen),
- •Eligibility for second line chemotherapy with gemcitabine,
- •ECOG performance scale 0 or 1,
- •Consent for the sampling and investigations of biological specimens as scheduled by the trial protocol,
- •Adequate bone marrow function: neutrophils >1.5 x 1E09/L, platelets >100 x 1E09/L, hemoglobin >9.0 g/dL,
- •Liver function tests (LFT) within the following range: Bilirubin <3 x ULN (Upper Limit of Normal); ASAT and ALAT <5 x ULN,
- •Adequate renal function: Creatinine <1.5 g/dL,
- •Adequate blood clotting: aPTT <39 sec, INR <1.2,
- •Normal thyroid function, i.e. TSH, fT3 and fT4 within the normal range (TSH: 0.4 - 4.0 mU/l, fT3: 2.0 - 4.2 ng/l, fT4: 8 - 18 ng/l)
- •Negative serology for HIV, HBV and HCV,
- •Negative Beta-HCG test in blood in woman of childbearing potential,
- •Use of adequate contraception in both genders, i.e. use of double-effective method of contraception for the entire participation in the trial.
排除标准
- •Eligibility for surgical treatment,
- •Symptomatic cerebral, pulmonal, and/or osseous metastases,
- •Peritoneal carcinosis,
- •Liver cirrhosis,
- •Splenectomy,
- •Relevant respiratory impairment, corresponding to the grade IV or V of the MRC Breathlessness Scale (stops for breath after walking about 100 meters or after a few minutes on level ground, or too breathless to leave the house, or breathless when undressing),
- •Positive anti-drug antibodies (ADAs) against ParvOryx,
- •Hospitalization due to other conditions than the pancreatic cancer within the last 3 months,
- •Chemotherapy within 2 weeks prior to the first administration of the IMP,
- •Signs of active, systemic infection within 7 days prior to the study inclusion (clinical symptoms (cough, running nose, burning sensation while urinating, apparent skin or wound infection) and/or increase of fever and/or deterioration of infection-specific laboratory parameters beyond changes apparently driven by the underlying pancreatic cancer),
- •Radiotherapy within 6 weeks prior to the study inclusion,
- •Contraindications for CT,
- •Known allergy to iodinated contrast media,
- •Participation in another interventional trial within the last 30 days,
- •Presumed contact with pregnant women and/or infants <12 months of age within two months after the first administration of the IMP.
研究组 & 干预措施
ParvOryx
ParvOryx given intravenously on four consecutive days (day 1 to 4) and intrametastatic six to thirteen days thereafter (day 7, 10 or 14).
干预措施: Parvovirus H-1 (H-1PV) (Drug)
结局指标
主要结局
Shedding of viral genomes [Vg]
时间窗: Up to 6 months after treatment beginning
Parameter: Concentration of Vg in saliva
Safety and tolerability of the IMP
时间窗: Up to 6 months after treatment beginning
Parameter: adverse events
Humoral immuneresponse to the IMP
时间窗: Up to 6 months after treatment beginning
Parameter: Serum concentration of anti-drug antibodies (ADA)
Pharmacokinetics of viral genomes [Vg]
时间窗: Up to 6 months after treatment beginning
Parameter: AUC in blood
次要结局
- Histo-immuno-pathological effects of the IMP in the hepatic metastasis(Up to 2 months after treatment beginning)
- Cellular immune response against viral proteins(Up to 6 months after treatment beginning)
- Clinical outcome(Up to 6 months after treatment beginning)
- Extent of virus replication in the hepatic metastasis(Up to 2 months after treatment beginning)