肿瘤细胞治疗研究
英文原题：Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas
这是一项 I 期注册临床试验，评估神经干细胞治疗胶质母细胞瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 36 例。试验地点：美国 · 杜阿尔特、斯坦福、芝加哥、温斯顿-塞勒姆（共 4 个中心）。登记号：NCT05139056。
不限性别 · ≥ 18 Years
纳入标准： * 年龄≥18岁。 * Karnofsky体能状态评分≥70%。 * 预期生存期≥3个月。 * 确定最大耐受治疗周期数（MTC）时：组织学确诊为3或4级胶质瘤（如胶质母细胞瘤、4级星形细胞瘤、3级星形细胞瘤或3级少突胶质细胞瘤）；该研究部分已完成。 * 入组治疗方案4或4a时：胶质母细胞瘤首次复发。 * 影像学显示幕上肿瘤复发。 * 高级别胶质瘤在既往脑部放疗和替莫唑胺治疗后复发或进展。 * 患者需要接受肿瘤切除手术。 * 神经外科医师判断，切除后的肿瘤腔与脑室之间预计无物理通道。 * ANC≥1000个/mm³；血小板≥100,000个/mm³；总胆红素≤2.0 mg/dL；AST（SGOT）≤机构ULN的4倍；血清肌酐≤机构ULN。 * 距末次靶向药物给药至少2周。 * 距末次贝伐珠单抗给药至少4周。若近期接受辅助替莫唑胺（每日给药5天、每28天重复），末次替莫唑胺给药后须间隔23天。 * 既往抗癌治疗的所有显著毒性已稳定至新的基线或已缓解。 * 所有受试者均须能理解并愿意签署书面知情同意书。 * 治疗对胎儿发育的影响尚不明确。有生育能力的女性及有性生活且可能使伴侣受孕的男性须同意在研究期间采用有效避孕方式；有生育能力者登记前≤2周妊娠试验阴性。 排除标准： * 多灶性疾病。 * 正在接受放疗、化疗或其他研究性药物。 * 既往接受过神经干细胞治疗。 * 既往治疗的任何>1级毒性尚未恢复，脱发除外。 * 无法接受脑部MRI。 * 慢性或活动性CNS病毒感染。 * 凝血障碍或出血性疾病。 * 有未控制疾病，包括持续或活动性感染。 * 其他活动性恶性肿瘤。 * 妊娠或哺乳期。 * 研究者认为可能妨碍安全监测要求或按方案完成治疗的严重躯体或精神疾病。
Inclusion Criteria: * Patient must be age \>= 18 years * Patient has a Karnofsky performance status of \>= 70% * Patient has a life expectancy of \>= 3 months * When determining the maximum tolerated number of treatment cycles (MTC): patient has a histologically confirmed diagnosis of a grade 3 or 4 glioma (eg., glioblastoma, grade 4 astrocytoma, grade 3 astrocytoma, grade 3 oligodendroglioma). (This part of the study has been completed). * When enrolling to Treatment Schedules 4 and 4a: patient has glioblastoma at first recurrence. * Imaging studies show evidence of recurrent, supratentorial tumor(s). * Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide * The patient must be in need of surgery for tumor resection * Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles * Absolute neutrophil count (ANC) of \>= 1000 cells/mm\^3 * Platelet count \>= 100,000 cells/mm\^3 * Total bilirubin =\< 2.0 mg/dl * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 4 times the institutional upper limit of normal * Serum creatinine =\< the institutional upper limit of normal * At least 2 weeks from taking the last dose of a targeted agent * At least 4 weeks from the last dose of bevacizumab For temozolomide, an interval of 23 days is required from the last dose administered if the patient was recently treated with adjuvant temozolomide, consisting of temozolomide daily for 5 days, repeated every 28 days. * At least 2 weeks from taking the last dose of a targeted agent. * At least 4 weeks from the last dose of bevacizumab. * All significant toxicities from previous anticancer therapy must have stabilized to a new baseline or resolved. * All participants must have the ability to understand and the willingness to sign a written informed consent. * The effects of this treatment on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients or who are able to impregnate their partner, must agree to use an effective method of contraception while participating in this study. Patients of childbearing potential must have a negative pregnancy test =\< 2 week prior to registration. Exclusion Criteria: * Patient has multi-focal disease. * Patient is receiving radiation, chemotherapy, or another investigational agent. * Patient has had prior therapy with neural stem cells. * Patient has not recovered from any toxicity (\> grade 1) of prior therapies, except alopecia. * Patient is unable to undergo a brain MRI. * Patient has chronic or active viral infections of the central nervous system (CNS). * Patient has a coagulopathy or bleeding disorder. * Patient has an uncontrolled illness including ongoing or active infection. * Patient has another active malignancy. * Patient is pregnant or breastfeeding. * A patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Incidence of adverse events · Assessed using the Common Terminology Criteria for Adverse Events version 5.0. · Up to 30 days post removal of Rickhams；Progression-free survival (PFS) · Will estimate the rate 90% confidence interval (CI) for PFS at 6 months and use Kaplan Meier methods to estimate median PFS for all study participants as well as for the cohorts of glioblastoma (GBM) participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 given once a week or every two weeks. · From the time of surgery to the event date of progression, assessed at 6 months]
次要终点：Neural Stem Cells-expressing CRAd-S-pk7 (NSC-CRAd-S-pk7) immunogenicity；NSC-CRAd-S-pk7 migration within the brain；NSC-CRAd-S-pk7 migration outside the brain；Disease response；Overall survival (OS)；Changes in HSPG and survivin expression；Changes in immune cell populations；Changes in tumor growth
患者接受标准肿瘤切除手术，术中将首剂研究药物注射至切除腔壁。随后通过手术时置入的导管，每周或每两周（取决于入组时间）给予另外3剂。
本Ⅰ期试验研究向脑内多次给予基于神经干细胞的溶瘤病毒疗法（NSC-CRAd-S-pk7），治疗首次复发的胶质母细胞瘤患者的安全性。NSC-CRAd-S-pk7由可靶向胶质母细胞瘤细胞的神经干细胞及其携带的杀癌病毒组成。多次给药可能杀伤更多肿瘤细胞。
This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence. NSC-CRAd-S-pk7 consists of neural stem cells that can target glioblastoma cells and carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.
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