Targeted Delivery of OncoVEX^GM-CSF by Endoscopic Ultrasound (EUS)-Guided Fine Needle Injection (FNI) in Patients With Irresectable Pancreatic Cancer: A Pilot Multinational Experiment on Safety and Proof of Concept
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 6
- 主要终点
- Number of Participants Positive for Anti-herpes Simplex Virus-1 (HSV-1) Antibodies
研究概览
简要总结
The purpose of the study is to assess the safety of injections of talimogene laherparepvec into patients with pancreatic cancer that cannot be removed by surgery. The study will also test whether the injections are effective in treating the tumor.
详细描述
Talimogene laherparepvec is a conditionally replication competent herpes simplex type-1 virus designed for use in solid tumors. It has been specifically modified to replicate in tumors and to provide a local source of the immune-stimulating cytokine, granulocyte macrophage colony stimulating factor (GM-CSF). It is injected directly into cancer tumors and is believed to destroy tumor cells by direct infection of the tumor cells and an enhanced immune response due to the release of tumor antigens and GM-CSF expression.
This was an open-label, dose-escalation study evaluating the safety and efficacy of talimogene laherparepvec administered by direct injection into pancreatic tumors using endoscopic ultrasound (EUS)-guided fine needle injection (FNI). Only 1 tumor mass within the body and tail of the pancreas was injected in any participant. The protocol called for evaluation of 4 dosing regimens in sequential cohorts of participants; however, cohort 4 was not opened for enrollment.
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
- •cytological or histological proof of adenocarcinoma of the pancreas
- •unresectable, locally advanced disease (isolated liver metastases are permitted)
- •tumors of at least 1 cm diameter at screening
- •measurable disease using Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- •failure of either standard therapy, OR any one of the following:
- •no alternative therapeutic of higher curative potential is available;
- •investigator determination that patient could not tolerate alternative therapeutic due to unacceptable toxicity; or,
- •patient refusal to be treated with available alternative therapeutic
- •age > 18 years
- •life expectancy > 3 months
- •adequate bone marrow function as indicated by:
- •White blood cells (WBC) ≥ 3.0 x 10^9/L
- •platelets ≥ 100 x 10^9/L
- •hemoglobin ≥ 8.5 gm/dL
- •adequate liver function as indicated by:
- •bilirubin < 1.5 x upper limit of normal (ULN)
- •alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x ULN in case of presence of liver metastasis
- •ALT or AST < 2.5 x ULN in case of absence of liver metastasis
- •adequate renal function as indicated by a serum creatinine level < 1.5 x ULN.
- •adequate hemostasis indicated by international normalized ratio (INR) ≤ 1.5
- •mentally, physically and geographically able to undergo treatment and follow-up
- •provided written informed consent
- •first patient in each cohort only: seropositive for herpes simplex virus type 1 (HSV1)
排除标准
- •history of other malignancy within two years prior to screening, except for prostate cancer (T1c, T2ab with definitive treatment, prostate-specific antigen (PSA) < 1 ng/ml, and without ongoing hormone suppression) or adequately treated in situ carcinoma of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin
- •cystic form of pancreatic cancer; microcystic disease may be eligible upon discussion with Medical Monitor
- •Common Terminology Criteria for Adverse Events (CTCAE) version 3 grade 2 or greater clinical pancreatitis within 8 weeks prior to dosing with OncoVEX^GM-CSF
- •other than metastases limited to the liver, imaging evidence of metastatic disease to any other organ or tissue
- •any serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
- •evidence of compromised immune function including but not limited to:
- •clinically significant absolute lymphocyte count < Lower Limit of Normal (LLN)
- •known human immunodeficiency virus (HIV), acute or chronic active hepatitis B, or hepatitis C infection;
- •concurrently taking HIV antiviral medications (e.g. protease inhibitors, azidothymidine, etc.)
- •received intravenous (IV), intramuscular (IM) or subcutaneous (SC) human gamma globulin within 6 months prior to dosing with OncoVEX^GM-CSF
- •patients taking immunosuppressive agents (e.g. cyclosporine, tacrolimus, or oral or systemic corticosteroids at a dose of > 10 mg/day of prednisone or equivalent).
- •pregnancy, lactation or lack of effective contraception in women of child-bearing potential (e.g., not post menopausal for > 2 years, or had tubal ligation); lack of effective contraception in men if the partner is of child-bearing potential; women must have been practicing an effective contraceptive method for at least three months prior to entry in to the trial (hormonal contraception or intrauterine device in conjunction with a barrier method); men must use a condom or be surgically sterilized
- •patients with active bacterial or viral infections that require treatment with systemic antibiotics or antiviral agents within 2 weeks prior to the first dose of OncoVEX^GM-CSF); (note: patients with active cold sores or other HSV1 infections must wait until those lesions have crusted over before receiving OncoVEX^GM-CSF)
- •surgery requiring general or spinal anesthesia within four weeks prior to dosing with OncoVEX^GM-CSF
- •Treatment with an investigational agent within 4 weeks prior to the first dose of OncoVEX^GM-CSF
- •serum carbohydrate antigen (CA)19.9 levels > 3000 U/mL at screening
- •evidence of ascites on screening abdominal computed tomography (CT) scan
结局指标
主要结局
Number of Participants Positive for Anti-herpes Simplex Virus-1 (HSV-1) Antibodies
时间窗: Week 0 (Day 1, predose) and Week 3
Anti-HSV-1 antibodies were detected using an enzyme-linked immunosorbent assay (ELISA).
Number of Participants With Talimogene Laherparepvec Detected in Blood and Urine
时间窗: Treatment Day 1 predose and 2, 6, 12 and 24 hours postdose, and Week 3 and 6 at (predose and 2 hours postdose.
Samples of blood and urine collected before and up to 24 hours after dosing were tested for the presence of talimogene laherparepvec deoxyribonucleic acid (DNA) using a validated quantitative polymerase chain reaction (qPCR) assay.
Number of Participants With Adverse Events
时间窗: From first dose of talimogene laherparepvec until 30 days after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively.
A serious adverse event is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important and significant medical event that, based upon appropriate medical judgment, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed above.
次要结局
- Number of Participants With Overall Objective Response(Every 6 weeks until 12 weeks after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively.)
- Change From Baseline in Sum of Longest Diameters of Injected Tumors(Baseline and Week 6, 12 and 18)
- Change From Baseline in Pain Intensity(Baseline and Weeks 3 and 6)