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

Study Identifier:
CAAA601A52101
CT.gov Identifier:
NCT05109728
EudraCT Identifier:
2021-003672-14
EU Trial (CTIS) Number:
2023-506719-17-00
Study Contact Information:
N/A
Study Complete

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Study Summary

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.

To investigate the safety of [68Ga]Ga-DOTA-TATE and describe its uptake characteristics in participants with Glioblastoma

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Brain
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18 - 100 Years
    Study Drug
  • Drug: Arm
    • Read More
  • Drug: 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.
  • Drug: Other: Temozolomide
  • Drug: 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)
  • Drug: Experimental: Group 3 - Recurrent GB
  • Drug: 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:
  • Drug: 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.
  • Drug: An infusion of 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each [177Lu]Lu-DOTA-TATE dose for renal protection.
  • Drug: All participants will receive up to 6 administrations of [177Lu]Lu-DOTA-TATE (initial dose 150 mCi with 3 provisional dose levels up to 250 mCi) using the Bayesian Optimal Interval design. Group 1 will receive [177Lu]Lu-DOTA-TATE every 4 weeks with concomitant radiotherapy and temozolomide, followed by temozolomide maintenance. Group 2 will receive [177Lu]Lu-DOTA-TATE every 4 weeks for 3 doses with radiotherapy then every 3 weeks as a single agent. Group 3 will receive [177Lu]Lu-DOTA-TATE only, every 3 weeks
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    Inclusion 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
    Exclusion 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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Brain