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Trial record 1 of 1 for:    CAAA601A52101
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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.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05109728
Recruitment Status : Recruiting
First Posted : November 5, 2021
Last Update Posted : January 25, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study aims to establish the recommended dose of [177Lu]Lu-DOTA-TATE in combination with the standard of care or as single agent in three different groups of participants with Glioblastoma. In addition, this study will investigate the safety of [68Ga]Ga-DOTA-TATE and describe its uptake characteristics in participants with Glioblastoma.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: [177Lu]Lu-DOTA-TATE Drug: [68Ga]Ga-DOTA-TATE Other: Temozolomide Other: Radiotherapy Phase 1

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 or Group 2 depending on O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status:

  • 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.
  • Participants in Group 2 will receive treatment with [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days for the first 3 doses (during the radiotherapy period) followed by every 3 weeks +/- 2 days as single agent, up to a total of 6 administrations. Radiotherapy will be initiated 7 to 10 days after the first administration of [177Lu]Lu-DOTA-TATE and will be delivered at a dose of 2 Gy/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 10, 2022
Estimated Primary Completion Date : May 31, 2024
Estimated Study Completion Date : June 2, 2025


Arm Intervention/treatment
Experimental: Group 1 - Newly diagnosed GB (methylated MGMT)
Participants with newly diagnosed glioblastoma with methylated MGMT, 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: [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 2: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 4 weeks (Day 1, Day 29 and Day 57) and every 3 weeks in Maintenance phase. 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

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

Experimental: Group 2 - Newly diagnosed GB (unmethylated MGMT)
Participants with newly diagnosed glioblastoma with unmethylated MGMT, will receive [177Lu]Lu-DOTA-TATE every 4 weeks +/- 2 days for the first 3 doses (starting 7 to 10 days prior to initiation of Radiotherapy (RT) and at week 4 and week 8 after Radiotherapy (RT) initiated) and every 3 weeks +/- 2 days for the following doses
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 2: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 4 weeks (Day 1, Day 29 and Day 57) and every 3 weeks in Maintenance phase. 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

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: Radiotherapy
2 Gy/day, 5 days per week followed by 2 days of rest, for 6 consecutive weeks

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: [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 2: [177Lu]Lu-DOTA-TATE, dose level 0 (150mCi) administered every 4 weeks (Day 1, Day 29 and Day 57) and every 3 weeks in Maintenance phase. 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

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)




Primary Outcome Measures :
  1. Group 1: Frequency of dose limiting toxicities (DLTs) [ Time Frame: 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.


  2. Group 2: Frequency of dose limiting toxicities (DLTs) [ Time Frame: 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 2: 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 RT. The 49 to 52 days observation period is depending on the start day of RT (i.e. 7-10 days post first [177Lu]Lu-DOTA-TATE dose). If RT is delayed for any reason, the DLT observation period will last until the completion of RT.


  3. Group 3: Frequency of dose limiting toxicities (DLTs) [ Time Frame: 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.



Secondary Outcome Measures :
  1. Incidence and severity of adverse events (AEs), serious AEs (SAEs) of [177Lu]Lu-DOTA-TATE [ Time Frame: Up to approximately 2 years (estimated final OS analysis) from date of first study treatment ]

    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.


  2. Incidence and severity of Adverse Events (AEs) and serious Adverse Events (SAEs) within 48 hours after [68Ga]Ga-DOTA-TATE infusion [ Time Frame: up to 48 hours following the start of [68Ga]Ga-DOTA-TATE administration ]
    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.

  3. Overall Objective Status as per modified Response Assessment in Neuro-Oncology (mRANO) criteria [ Time Frame: Up to approximately 2 years (estimated final OS analysis) from date of first study treatment ]
    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.

  4. Progression-Free Survival (PFS) [ Time Frame: 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) ]
    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.

  5. Overall Survival (OS) [ Time Frame: Up to approximately 2 years (estimated final OS analysis) from date of first study treatment ]
    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.

  6. Groups 1 and 2: Time activity curves (TACs) [ Time Frame: 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) ]
    Time activity curves (TACs), describing percentage (%) of the activity injected vs time in blood, organs and tumor lesions

  7. Groups 1 and 2: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    Absorbed radiation doses of [177Lu]Lu-DOTA-TATE in organs and tumor lesions will be summarized with descriptive statistics.

  8. Groups 1 and 2: Concentration of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  9. Groups 1 and 2: Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  10. Groups 1 and 2: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  11. Groups 1 and 2: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  12. Groups 1 and 2: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  13. Groups 1 and 2: Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  14. Groups 1 and 2: Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  15. Groups 1 and 2: Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  16. Groups 1 and 2: Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  17. Group 3: Time activity curves (TACs) [ Time Frame: 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) ]
    Time activity curves (TACs), describing percentage (%) of the activity injected vs time in blood, organs and tumor lesions

  18. Group 3: Absorbed radiation doses of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    Absorbed radiation doses of [177Lu]Lu-DOTA-TATE in organs and tumor lesions will be summarized with descriptive statistics.

  19. Group 3: Concentration of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  20. Group 3: Observed maximum plasma concentration (Cmax) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  21. Group 3: Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  22. 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 [ Time Frame: 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) ]
    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.

  23. Group 3: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  24. Group 3: Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  25. Group 3: Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  26. Group 3: Terminal elimination half-life (T^1/2) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  27. Group 3: Terminal-Phase Disposition Rate Constant (λz) of [177Lu]Lu-DOTA-TATE [ Time Frame: 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) ]
    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.

  28. Quantification of [177Lu]Lu-DOTA-TATE excreted from the body in urine [ Time Frame: From the start of [177Lu]Lu-DOTA-TATE infusion until the first whole body planar imaging ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • Presence of Gadolinium enhancing tumor in pre-surgery magnetic resonance imaging (MRI)
  • Karnofsky Performance Score (KPS) >= 70 %

Recurrent Glioblastoma:

  • Participant has experienced first or second recurrence of their glioblastoma, after standard or experimental therapy that includes prior radiation therapy
  • 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 scan at the tumor region
  • Presence of Gadolinium enhancement in the tumor region in MRI at the time of diagnosis of tumor recurrence

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

Newly Diagnosed Glioblastoma:

• Any prior treatment for glioma of any grade

Recurrent Glioblastoma:

  • Early disease progression prior to 3 months from the completion of radiotherapy
  • More than 2 prior lines for systemic therapy
  • Previous treatment with bevacizumab

Exclusion Criteria (France Only)

• Known severe chronic or active infections


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05109728


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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France
Novartis Investigative Site Recruiting
Bron, France, 69677
Novartis Investigative Site Recruiting
Marseille Cedex 05, France, 13885
Portugal
Novartis Investigative Site Recruiting
Porto, Portugal, 4200-072
Spain
Novartis Investigative Site Recruiting
Granada, Andalucia, Spain, 18014
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Switzerland
Novartis Investigative Site Recruiting
Zurich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05109728    
Other Study ID Numbers: CAAA601A52101
2021-003672-14 ( EudraCT Number )
First Posted: November 5, 2021    Key Record Dates
Last Update Posted: January 25, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Glioblastoma
GBM
Radioligand Therapy
RLT
[177Lu]Lu-DOTA-TATE
Temozolomide
O-6-methylguanine-DNA methyltransferase
MGMT
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Lutetium Lu 177 dotatate
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Chelating Agents
Sequestering Agents
Radiopharmaceuticals