A Phase I/II Study of Isolated Limb Infusion and Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Optimal tolerated dose (OTD) of CRAd 3/5
研究概览
简要总结
This phase I/II trial studies the safety, best dose and effectiveness of targeted gene therapy combined with isolated limb infusion (ILI) of melphalan and dactinomycin for treating patients with advanced extremity melanoma that cannot be removed by surgery. Adding gene therapy to a standard chemotherapy regimen in the isolated limb may enhance anti-cancer effects by inducing a systemic immune response against the tumor cells.
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
- •Patient must have histologically or cytologically confirmed diagnosis of melanoma with advanced, unresectable primary or in transit metastasis
- •Patient must have measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with caliper measurement for superficial lesions or computed tomography (CT) scan for deeper lesions; additionally, patients must have no evidence of disease beyond the affected extremity on positron emission tomography (PET)/CT scan
- •Patients may have undergone any previous systemic chemotherapy with a treatment free period of > 4 weeks prior to enrolling on this clinical trial
- •Patient must be > 18 years of age.-Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2, Karnofsky >= 60%
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x IULN
- •Creatinine within normal institutional limits
- •OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- •Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an institutional review board (IRB) approved written informed consent document
排除标准
- •Patients must not have had previous oncolytic viral therapy
- •Patient must not be receiving any other investigational agents
- •Patient must not have known brain metastases; patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan or dactinomycin or other agents used in the study
- •Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Patient must not be pregnant and/or breastfeeding
- •Patient must not be known to be human immunodeficiency virus (HIV)-positive or otherwise immunocompromised (i.e., patient has undergone organ/bone marrow transplant on immunosuppression, patient is or has recently undergone treatment with toxic chemotherapy for another malignancy, etc.) as there is a risk of complications in the use of adenovirus therapy in these patients
研究组 & 干预措施
Treatment (targeted gene therapy and ILI)
Patients receive melphalan and dactinomycin via ILI. Patients then receive CRAd 3/5-delta via ILI.
干预措施: dactinomycin (Biological)
Treatment (targeted gene therapy and ILI)
Patients receive melphalan and dactinomycin via ILI. Patients then receive CRAd 3/5-delta via ILI.
干预措施: melphalan (Drug)
Treatment (targeted gene therapy and ILI)
Patients receive melphalan and dactinomycin via ILI. Patients then receive CRAd 3/5-delta via ILI.
干预措施: Conditionally replicative adenovirus 3/5-delta (Biological)
结局指标
主要结局
Optimal tolerated dose (OTD) of CRAd 3/5
时间窗: 14 days
Defined as the dose level at which \> 50% of target lesion viral infectivity is achieved and \< 2 of 6 patients have dose limiting toxicities.
Response rate (complete response [CR] + partial response [PR]) of CRAd 3/5-delta in combination with standard M-ILI (Phase II)
时间窗: 3 months
Assessed using revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Progression Free Survival (Phase II)
时间窗: 2 years
Duration of time from start of treatment to time of progression or death, whichever occurs first.
次要结局
- Safety of CRAd 3/5-delta in combination with standard M-ILI(2 years)
- Infectivity rate of CRAd 3/5-delta(2 days; baseline and day 1 or 2 post treatment)