A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination With Radiotherapy With or Without Temozolomide and in Recurrent Glioblastoma as Single Agent
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 65
- 试验地点
- 14
- 主要终点
- Group 1: Frequency of dose limiting toxicities (DLTs)
研究概览
简要总结
A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Glioblastoma in Combination with Standard of Care and in Recurrent Glioblastoma as a Single Agent
详细描述
The study for each participant consists of a Screening period, a Treatment period and a 12-month Follow-up period.
During the screening period of up to 6 weeks before starting GBM treatment, each participant will be assessed for somatostatin receptor (SSTR) expression by [68Ga]Ga-DOTA-TATE imaging PET/scan.
Eligible participants with newly diagnosed glioblastoma will be assigned to Group 1 :
• Participants in Group 1 (concomitant radiotherapy + temozolomide and temozolomide maintenance) will receive treatment with [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days, up to 6 administrations. Radiotherapy and temozolomide will be administered 7 to 10 days after the first administration of [177Lu]Lu-DOTA-TATE. Temozolomide will be administered orally at a dose of 75 mg/m2/day during the concomitant period, concurrently with radiotherapy. Radiotherapy will be delivered at a dose of 2 Gray (Gy)/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks with a total dose of 60 Gy (without interruption). During the maintenance period, there is an intra-patient dose escalation in temozolomide treatment. The dosage of temozolomide is 150 mg/m2 in Cycle 1 of maintenance period, and then to 200 mg/m2 in Cycle 2 and beyond in the maintenance period, if 150 mg/m2 temozolomide treatment is well tolerated in Cycle 1.
Eligible participants with recurrent glioblastoma will be assigned to Group 3 and will receive [177Lu]Lu-DOTA-TATE as single agent treatment every 3 weeks +/- 2 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Common Criteria:
- •Participant is >= 18 years on the day of signing informed consent form
- •Histologically confirmed glioblastoma
- •Adequate bone marrow, organ function and electrolyte values
- •Newly diagnosed glioblastoma (Group 1):
- •Presence of Gadolinium enhancing tumor in pre-surgery magnetic resonance imaging (MRI)
- •Karnofsky Performance Score (KPS) >= 70 %
- •Recurrent glioblastoma (Group 3 dose Escalation only):
- •Participant has experienced first or second recurrence of their glioblastoma, after standard or experimental therapy that includes prior EBRT
- •Recurrent glioblastoma (Group 3 dose escalation and expansion):
- •Evidence of recurrent disease demonstrated by disease progression using modified Response Assessment in Neuro-Oncology (mRANO) criteria
- •KPS >= 60 %
- •[68Ga]Ga-DOTA-TATE uptake by positron emission tomography/computed tomography (PET/CT) or PET/MRI at the tumor region
- •Presence of Gadolinium enhancement in the tumor region in MRI at the time of diagnosis of tumor recurrence
- •A second surgery for glioblastoma is allowed provided that the following criteria are met:
- •Residual and measurable disease post-surgery is not required but surgery must have confirmed the diagnosis of recurrence
- •Surgery completed at least 2 weeks prior to study treatment initiation, with post-surgery recovery without any complications related to surgical procedure
- •Recurrent glioblastoma (Group 3 Dose Expansion only):
- •Patients experiencing first recurrence of their glioblastoma, after standard or experimental therapy that includes prior EBRT
排除标准
- •Common Criteria:
- •Participant is receiving additional, concurrent, active therapy for glioblastoma outside of the trial
- •Extensive leptomeningeal disease
- •History of another active malignancy in the previous 3 years prior to study entry
- •Prior administration of a radiopharmaceutical unless 10 or more effective half-lives have elapsed before injection of [68Ga]Ga-DOTA-TATE or [177Lu]Lu-DOTA-TATE
- •Newly diagnosed glioblastoma (Group 1):
- •Any prior treatment for glioma of any grade
- •Recurrent glioblastoma (Group 3 dose escalation and expansion):
- •Early disease progression prior to 3 months from the completion of radiotherapy
- •Previous treatment with bevacizumab for the treatment of glioblastoma with therapeutic intent, or with bevacizumab as supportive therapy (e.g. edema reduction) within 60 days of initiation of study treatment
- •Recurrent glioblastoma (Group 3 dose escalation only):
- •More than 2 prior lines for systemic therapy
- •Recurrent glioblastoma (Group 3 dose expansion only):
- •More than 1 prior line for systemic therapy
研究组 & 干预措施
Group 1 - Newly diagnosed GB
Participants with newly diagnosed glioblastoma will receive [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days, starting 7 to 10 days prior to initiation of Radiotherapy (RT) and Temozolomide (TMZ)
干预措施: [177Lu]Lu-DOTA-TATE (Drug)
Group 3 - Recurrent GB
Participants with recurrent glioblastoma will receive [177Lu]Lu-DOTA-TATE as single agent therapy every 3 weeks +/- 2 days
干预措施: [68Ga]Ga-DOTA-TATE (Drug)
Group 1 - Newly diagnosed GB
Participants with newly diagnosed glioblastoma will receive [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days, starting 7 to 10 days prior to initiation of Radiotherapy (RT) and Temozolomide (TMZ)
干预措施: [68Ga]Ga-DOTA-TATE (Drug)
Group 3 - Recurrent GB
Participants with recurrent glioblastoma will receive [177Lu]Lu-DOTA-TATE as single agent therapy every 3 weeks +/- 2 days
干预措施: [177Lu]Lu-DOTA-TATE (Drug)
Group 1 - Newly diagnosed GB
Participants with newly diagnosed glioblastoma will receive [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days, starting 7 to 10 days prior to initiation of Radiotherapy (RT) and Temozolomide (TMZ)
干预措施: Temozolomide (Other)
Group 1 - Newly diagnosed GB
Participants with newly diagnosed glioblastoma will receive [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days, starting 7 to 10 days prior to initiation of Radiotherapy (RT) and Temozolomide (TMZ)
干预措施: Radiotherapy (Other)
结局指标
主要结局
Group 1: Frequency of dose limiting toxicities (DLTs)
时间窗: 49 to 52 days starting from first administration of [177Lu]Lu-DOTA-TATE
A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that meets any of the criteria defining dose-limiting toxicities and with an onset during the DLT observation period specified for the group. • Group 1: DLT observation period of 49 to 52 days starting from the first administration of \[177Lu\]Lu-DOTA-TATE (Day 1) and ending with the completion of concomitant RT and TMZ. The 49 to 52 days observation period is depending on the start day of concomitant RT and TMZ (i.e. 7-10 days post first \[177Lu\]Lu-DOTA-TATE dose). If the concomitant RT and TMZ is delayed for any reason, the DLT observation period will last until the completion of the concomitant treatment. If RT or TMZ is delayed, the DLT observation period will last until the last administered dose, whichever occurs later.
Group 3: Frequency of dose limiting toxicities (DLTs)
时间窗: 42 days starting from first administration of [177Lu]Lu-DOTA-TATE
A dose-limiting toxicity (DLT) is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that meets any of the criteria defining dose-limiting toxicities and with an onset during the DLT observation period specified for the group. • Group 3: DLT observation period of 42 days starting from the first administration of \[177Lu\]Lu-DOTA-TATE (Day 1) i.e. accounting for 2 cycles of Lu\]Lu-DOTA-TATE.
次要结局
- Incidence and severity of adverse events (AEs), serious AEs (SAEs) of [177Lu]Lu-DOTA-TATE(Up to approximately 2 years (estimated final OS analysis) from date of first study treatment)
- Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs) within 48 hours after [68Ga]Ga-DOTA-TATE infusion(up to 48 hours following the start of [68Ga]Ga-DOTA-TATE administration)
- Overall Objective Status as per modified Response Assessment in Neuro-Oncology (mRANO) criteria(Up to approximately 2 years (estimated final OS analysis) from date of first study treatment)
- Overall Survival (OS)(Up to approximately 2 years (estimated final OS analysis) from date of first study treatment)
- Progression-Free Survival (PFS)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed for up to 2 years (estimated final OS analysis))
- Group 1: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Time activity curves (TACs)(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Concentration of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 3: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Groups 1: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 1: Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATE(Week 5 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 5 Day 2 (24 hours post-dose), Week 5 Day 3 (48 hours post-dose), Week 5 Day 8 (168 hours post-dose))
- Group 3: Time activity curves (TACs)(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Concentration of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Group 3: Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATE(Week 4 Day 1 (pre-dose, before the end of infusion, 2 hours post-dose, 6 hours post-dose), Week 4 Day 2 (24 hours post-dose), Week 4 Day 3 (48 hours post-dose), Week 4 Day 8 (168 hours post-dose))
- Quantification of [177Lu]Lu-DOTA-TATE excreted from the body in urine(From the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging)