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.

NCT05109728 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAAA601A521012021-003672-14
• Study Type: interventional
• Target: 65
• Locations: 5 countries
• Sites: 14

Brief Summary

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

Conditions

Glioblastoma

Keywords

Glioblastoma; GBM; Radioligand Therapy; RLT; [177Lu]Lu-DOTA-TATE; Temozolomide; O-6-methylguanine-DNA methyltransferase; MGMT

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (28)

• 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

• 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)

• Overall Survival (OS)

  Up to approximately 2 years (estimated final OS analysis) from date of first study treatment

Study Arms (2)

Group 1 - Newly diagnosed GB

EXPERIMENTAL

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: [177Lu]Lu-DOTA-TATE; Drug: [68Ga]Ga-DOTA-TATE; Other: Temozolomide; Other: Radiotherapy

Group 3 - Recurrent GB

EXPERIMENTAL

Participants with recurrent glioblastoma will receive \[177Lu\]Lu-DOTA-TATE as single agent therapy every 3 weeks +/- 2 days

Drug: [177Lu]Lu-DOTA-TATE; Drug: [68Ga]Ga-DOTA-TATE

Interventions

[177Lu]Lu-DOTA-TATE DRUG

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.

Also known as: Lutathera, Lutetium (177Lu)oxodotreotide, Lutetium Lu 177dotatate

Group 1 - Newly diagnosed GB; Group 3 - Recurrent GB

[68Ga]Ga-DOTA-TATE DRUG

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)

Group 1 - Newly diagnosed GB; Group 3 - Recurrent GB

Temozolomide OTHER

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)

Group 1 - Newly diagnosed GB

Radiotherapy OTHER

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

Group 1 - Newly diagnosed GB

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Col Uni Med Center New York Presby

New York, New York, 10032, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MD Anderson Cancer Center Uni of Te

Houston, Texas, 77030, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53792-1615, United States

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Porto, 4200-072, Portugal

Location

Novartis Investigative Site

Granada, Andalusia, 18014, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

lutetium Lu 177 dotatate; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 5, 2021
• Study Start: May 10, 2022
• Primary Completion: December 3, 2025
• Study Completion (Estimated): July 31, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CH (2); PT (1); FR (2); ES (5)