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.

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

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

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: [68Ga]Ga-DOTA-TATE; Other: Temozolomide; Other: Radiotherapy; Drug: [177Lu]Lu-DOTA-TATE

Detailed Description

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.

An infusion of sterile 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each [177Lu]Lu-DOTA-TATE dose for renal protection.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• France
  • Bron, France, 69677
    • Recruiting
    • Novartis Investigative Site
  • Marseille Cedex 05, France, 13885
    • Recruiting
    • Novartis Investigative Site
• Portugal
  • Porto, Portugal, 4200-072
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28050
    • Recruiting
    • Novartis Investigative Site
  • Andalucia
    • Granada, Andalucia, Spain, 18014
      • Recruiting
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Recruiting
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Recruiting
      • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Novartis Investigative Site
  • Zurich, Switzerland, 8091
    • Recruiting
    • Novartis Investigative Site
• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh University of Pittsburgh (2)
      • Principal Investigator: Jan Drappatz
      • Contact: Carolyn Stone; Phone Number: 412-648-6575; Email: stonecj@upmc.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center/University of Texas MDACC
      • Principal Investigator: Nazanin K Majd
      • Contact: Chetna Wathoo; Email: CWathoo@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

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:

  1. Residual and measurable disease post-surgery is not required but surgery must have confirmed the diagnosis of recurrence

  2. 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

Key Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 3 - Recurrent GB; Participants with recurrent glioblastoma will receive [177Lu]Lu-DOTA-TATE as single agent therapy every 3 weeks +/- 2 days	Drug: [68Ga]Ga-DOTA-TATE; 2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi); Drug: [177Lu]Lu-DOTA-TATE; Group 1: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 4 weeks. Three provisional dose levels (Dose level +2: 250 mCi; Dose level +1: 200 mCi; Dose level -1: 100 mCi) will be assessed. Group 3: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 3 weeks. Three provisional dose levels (Dose level +2: 250 mCi; Dose level +1: 200 mCi; Dose level -1: 100 mCi) will be assessed.; Other Names: Lutathera; Lutetium (177Lu)oxodotreotide; Lutetium Lu 177dotatate
Experimental: 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)	Drug: [68Ga]Ga-DOTA-TATE; 2 MBq/kg of body weight (0.054 mCi/kg), with a minimum dose of 100 MBq (2.7 mCi) and maximum dose of 200 MBq (5.4 mCi); Other: Temozolomide; Concomitant Phase: Temozolomide 75mg/m2/d p.o until last day of EBRT. Maintenance Phase: Temozolomide p.o 150 mg/m2/d during cycle 1 then 200 mg/m2/d for the following cycles if tolerated well in Cycle 1. 6 cycles total (1 cycle = every 28 days); Other: Radiotherapy; 2 Gy/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks; Drug: [177Lu]Lu-DOTA-TATE; Group 1: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 4 weeks. Three provisional dose levels (Dose level +2: 250 mCi; Dose level +1: 200 mCi; Dose level -1: 100 mCi) will be assessed. Group 3: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 3 weeks. Three provisional dose levels (Dose level +2: 250 mCi; Dose level +1: 200 mCi; Dose level -1: 100 mCi) will be assessed.; Other Names: Lutathera; Lutetium (177Lu)oxodotreotide; Lutetium Lu 177dotatate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group 1: Frequency of dose limiting toxicities (DLTs)	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.	49 to 52 days starting from first administration of [177Lu]Lu-DOTA-TATE
Group 3: Frequency of dose limiting toxicities (DLTs)	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.	42 days starting from first administration of [177Lu]Lu-DOTA-TATE

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs), serious AEs (SAEs) of [177Lu]Lu-DOTA-TATE	The distribution of adverse events of [177Lu]Lu-DOTA-TATE will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. During the follow up period, all AEs and lab abnormalities will be collected within 8 weeks after the last dose of study treatment. For participants with study drug related AEs, they will be followed until resolution or until the End of Study, whichever occurs first. Apart from that, only survival information, SAEs, that are considered related to study drug by the Investigator, and AEs of secondary hematological malignancies will be collected until the end of follow up period every 8 weeks.	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	The distribution of adverse events of [68Ga]Ga-DOTA-TATE will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.	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	According to modified RANO, the objective overall status combines the radiographic response on target lesions, new disease, neurological status and use of steroids and the result is reported as confirmed or preliminary CR, confirmed or preliminary PR, stable disease, confirmed or preliminary disease progression. The best objective overall status achieved during the study will be summarized using frequency and percentage. The rate of confirmed complete or partial response will be summarized using point estimate and 2-sided exact binomial 95% confidence interval (Clopper-Pearson) and presented by dose level within each group.	Up to approximately 2 years (estimated final OS analysis) from date of first study treatment
Progression-Free Survival (PFS)	Progression-Free Survival (PFS) is defined as the time from the date of first dose to the date of confirmed progression according to modified RANO or death due to any cause. If no PFS event is observed, PFS will be censored at the date of the last adequate tumor assessment prior to data cut-off date and start of new anti neoplastic therapy, whichever comes first. PFS will be analyzed in the FAS population and results will be presented for each dose level within each group. The PFS distribution will be estimated using the Kaplan-Meier method.	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)
Overall Survival (OS)	Overall Survival (OS) is defined as the time from date of first dose to date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date). OS will be analyzed in the FAS population and results will be presented for each dose level within each group. The OS distribution will be estimated using the Kaplan-Meier method.	Up to approximately 2 years (estimated final OS analysis) from date of first study treatment
Group 3: Time activity curves (TACs)	Time activity curves (TACs), describing percentage (%) of the activity injected vs time in blood, organs and tumor lesions	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	Absorbed radiation doses of [177Lu]Lu-DOTA-TATE in organs and tumor lesions will be summarized with descriptive statistics.	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	Blood samples for radioactivity measurement will be collected before the start of [177Lu]Lu-DOTA-TATE infusion, at the end of [177Lu]Lu-DOTA-TATE infusion, then at 2 h, 6 h, 24 h, 48 h and 168 h after the end of [177Lu]Lu-DOTA-TATE infusion for participants undergoing dosimetry. Blood samples will be drawn in heparinized tubes. Radioactivity measurements on blood will be performed locally on site, using a gamma-counter.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.	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: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Tmax will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUClast will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUCinf will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. CL will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Terminal-Phase Disposition Rate Constant will be listed and summarized using descriptive statistics.	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	All excreted urine from the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging will be collected, its volume measured and the radioactivity concentration kilobecquerel per milliliter (kBq/mL) determined in order to calculate the total radioactivity excreted from the body from the start of [177Lu]Lu-DOTA-TATE infusion to the time of the first scan. If no urine is excreted from the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging, no urine dosimetry is necessary.	From the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging
Group 1: Time activity curves (TACs)	Time activity curves (TACs), describing percentage (%) of the activity injected vs time in blood, organs and tumor lesions	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: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE	Absorbed radiation doses of [177Lu]Lu-DOTA-TATE in organs and tumor lesions will be summarized with descriptive statistics.	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	Blood samples for radioactivity measurement will be collected before the start of [177Lu]Lu-DOTA-TATE infusion, at the end of [177Lu]Lu-DOTA-TATE infusion, then at 2 h, 6 h, 24 h, 48 h and 168 h after the end of [177Lu]Lu-DOTA-TATE infusion for participants undergoing dosimetry. Blood samples will be drawn in heparinized tubes. Radioactivity measurements on blood will be performed locally on site, using a gamma-counter.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.	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)
Groups 1: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Tmax will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUClast will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUCinf will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. CL will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.	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	Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Terminal-Phase Disposition Rate Constant will be listed and summarized using descriptive statistics.	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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Estimated): July 28, 2025
• Study Completion (Estimated): July 28, 2026

Study Registration Dates

• First Submitted: October 27, 2021
• First Submitted That Met QC Criteria: October 27, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Temozolomide; GBM; Glioblastoma; Radioligand Therapy; RLT; [177Lu]Lu-DOTA-TATE; MGMT; O-6-methylguanine-DNA methyltransferase
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Radiopharmaceuticals; Chelating Agents; Sequestering Agents; Temozolomide; Lutetium Lu 177 dotatate; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Other Study ID Numbers: CAAA601A52101; 2021-003672-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No