A Phase 1 Window-of-Opportunity Study of SRN-101 Administered Prior to Surgical Resection in Adults With Recurrent High-Grade Glioma.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Proportion of participants reporting treatment-emergent adverse events
研究概览
简要总结
SRN-101 is designed to destroys tumor cells while simultaneously activating the immune system to fight cancer. This is a first in human, single arm study to evaluate SRN-101 for the treatment of adults with recurrent high-grade glioma (rHGG) who are eligible for resection.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of intratumoral administration of SRN-101 in participants with recurrent high-grade glioma (rHGG) undergoing resection.
II. To evaluate the biologic activity of SRN-101.
EXPOLORATORY OBJECTIVES:
I. To assess immunologic response to SRN-101. II. To identify potential pharmacodynamics biomarkers for SRN-101 activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Male or female ≥ 18 years of age.
- •Participants have received at least one prior line of standard-of-care treatment for high-grade glioma (HGG). Specifically, participants have received prior surgery that resulted in histopathologic diagnosis followed by treatment with radiation alone and/or radiation plus temozolomide.
- •Participants with recurrent high-grade glioma (rHGG) for whom resection is planned, and with a lesion that is accessible to convection-enhanced delivery (CED) therapy. Eligible tumor types include central nervous system (CNS) World Health Organization (WHO) Grade 4 astrocytoma isocitrate dehydrogenase (IDH) wild-type (WT) (i.e., glioblastoma), WHO Grade 4 astrocytoma IDH mutated, WHO Grade 3 astrocytoma IDH WT or mutated, and WHO Grade 3 oligodendroglioma IDH mutated, 1p19q codeleted. Participants may have had multiple recurrences.
- •Tumors must be supratentorial in location, and participants can only have a single lesion that is ≥ 1 centimeter and ≤ 4 centimeters in diameter.
- •Performance Level using the Karnofsky score ≥ 70%. Note: Neurologic deficits in participants with CNS tumors must have been stable for at least 7 days with no new deficits prior to study enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the Karnofsky performance score.
- •Predictable life expectancy of at least 3 months.
- •Participants must have adequately recovered from the acute toxic effects of all prior anti-cancer chemotherapy and must be at least 3 weeks from previous cytotoxic chemotherapy, 4 weeks from prior radiation therapy, and at least 2 weeks from any major surgery, with evidence of adequate wound healing.
- •Participants must have adequate organ function based on laboratory assessments obtained within 21 days prior to study treatment. Laboratory values obtained as part of standard of care within this timeframe may be used to satisfy eligibility criteria.
- •Adequate bone marrow function:
- •absolute neutrophil count ≥1,500/microliter (mcL) platelets ≥100,000/mcL
- •Adequate hepatic function:
- •total bilirubin ≤ 2x upper limit of normal (ULN) for their age Aspartate aminotransferase (AST)serum glutamic-oxaloacetic transaminase (SGOT) ≤2 X institutional upper limit of normal alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤2 X institutional upper limit of normal Serum albumin ≥ 2 g/dL
- •Adequate renal function:
- •creatinine ≤ 1.5 x within institutional upper limit of normal OR creatinine clearance radioisotope (GFR) ≥ 70 mL/min/1.73 m2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2
- •Adequate coagulation:
- •Prothrombin time and international normalized ratio ≤ 1.5x ULN
- •Note: Participants receiving anticoagulant therapy must be able to safely discontinue anticoagulation per institutional guidelines and the treating neurosurgeon's discretion prior to infusion of SRN-
- •Participants with seizure disorders may be enrolled if on a stable anticonvulsant dose and not experiencing refractory seizures in the last 3 months.
- •Agree to participate in the long-term safety follow-up.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Disseminated disease or multifocal disease.
- •Pregnant or breastfeeding. Participants of childbearing potential and male participants with female partners of childbearing potential must agree to always use highly effective forms of contraception during the course of the study and for at least 3 months after completion of study intervention. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Participants of childbearing potential must have a negative blood pregnancy test within 21 days of commencement of study intervention. Participants must refrain from donating sperm during the course of the study and for at least 3 months after completion of study intervention.
- •History of active liver disease, including Hepatitis B or Hepatitis C or human immunodeficiency virus (HIV).
- •Another concurrent tumor immunotherapy.
- •Initiation and/or escalation of systemic immunosuppressive therapy (including corticosteroids) within 7 days prior to study initiation, except protocol-required peri-procedural dexamethasone. Participants already on dexamethasone (at a maximum dose of 4 mg per day) are eligible.
- •Known or suspected hypersensitivity to Gadoteridol, its excipients, or other gadolinium-based contrast agents.
- •Recent onset of neurologic dysfunction or abnormality that is deemed by the Investigator to prevent patient participation.
- •Inability, or potential inability, to comply with the safety monitoring requirements of the study, as determined by the Investigator's opinion.
- •Other comorbidities that the Investigator believes will negatively impact the participant's ability to benefit from or tolerate this study.
- •Inability to undergo an MRI.
- •Radiographic evidence that the target lesion or an associated treatment or resection cavity directly communicates with the ventricular system, or determination by the treating neurosurgeon that adequate CED of the target lesion cannot be performed without clinically meaningful leakage of infusate into a cerebral spinal fluid (CSF) space.
研究组 & 干预措施
SRN-101 Run-in Dose Level - 1.6E12 vg (First Participant)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 1.6E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: Blood Specimen Collection (Procedure)
SRN-101 Run-in Dose Level - 1.6E12 vg (First Participant)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 1.6E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: Surgical Resection (Procedure)
SRN-101 Run-in Dose Level - 1.6E12 vg (First Participant)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 1.6E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
SRN-101 Dose Level - 5.0E12 vg (Subsequent Participants)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 5.0E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: Blood Specimen Collection (Procedure)
SRN-101 Dose Level - 5.0E12 vg (Subsequent Participants)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 5.0E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: Surgical Resection (Procedure)
SRN-101 Dose Level - 5.0E12 vg (Subsequent Participants)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 5.0E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
SRN-101 Dose Level - 5.0E12 vg (Subsequent Participants)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 5.0E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: SRN-101 (Drug)
SRN-101 Run-in Dose Level - 1.6E12 vg (First Participant)
Participants will receive a single intratumoral administration of SRN-101 at a dose of 1.6E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.
干预措施: SRN-101 (Drug)
结局指标
主要结局
Proportion of participants reporting treatment-emergent adverse events
时间窗: Up to 21 days
Treatment-emergent adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Proportion of participants reporting adverse events of special interest
时间窗: Up to 21 days
Adverse events of special interest (AESI) will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Quantification of SRN-101 vector copy number
时间窗: Up to 21 days
SRN-101 vector copy number will be measured in resected tumor tissue, peripheral blood, and cerebrospinal fluid (if available) using quantitative polymerase chain reaction (qPCR). Results will be summarized descriptively.
Quantification of hIFNβ transcript and protein levels
时间窗: Up to 21 days
hIFNβ transcript and protein levels will be measured in resected tumor tissue, peripheral blood, and cerebrospinal fluid (CSF; if available) using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results will be summarized descriptively.
次要结局
未报告次要终点
研究者
Nicholas Butowski
Principal Investigator
University of California, San Francisco