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.

NCT ID: NCT05109728

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-10

Study Completion Date

2026-07-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Glioblastoma

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

[177Lu]Lu-DOTA-TATE

Intervention Type 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.

[68Ga]Ga-DOTA-TATE

Intervention Type 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)

Temozolomide

Intervention Type 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)

Radiotherapy

Intervention Type OTHER

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

Group 3 - Recurrent GB

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

Group Type EXPERIMENTAL

[177Lu]Lu-DOTA-TATE

Intervention Type 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.

[68Ga]Ga-DOTA-TATE

Intervention Type 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)

Interventions

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[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.

Intervention Type 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)

Intervention Type DRUG

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)

Intervention Type OTHER

Radiotherapy

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

Intervention Type OTHER

Other Intervention Names

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Lutathera Lutetium (177Lu)oxodotreotide Lutetium Lu 177dotatate

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Col Uni Med Center New York Presby

New York, New York, United States

Site Status RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

MD Anderson Cancer Center Uni of Te

Houston, Texas, United States

Site Status RECRUITING

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

Site Status RECRUITING

Novartis Investigative Site

Bron, , France

Site Status RECRUITING

Novartis Investigative Site

Marseille, , France

Site Status RECRUITING

Novartis Investigative Site

Porto, , Portugal

Site Status RECRUITING

Novartis Investigative Site

Granada, Andalusia, Spain

Site Status COMPLETED

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status COMPLETED

Novartis Investigative Site

Barcelona, , Spain

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

Lausanne, , Switzerland

Site Status ACTIVE_NOT_RECRUITING

Novartis Investigative Site

Zurich, , Switzerland

Site Status RECRUITING

Countries

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United States France Portugal Spain Switzerland

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

Phone: 1-888-669-6682

Email: [email protected]

Novartis Pharmaceuticals

Role: CONTACT

Phone: +41613241111

Facility Contacts

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Rasha Baig

Role: primary

Millie Metchick

Role: primary

Chetna Wathoo

Role: primary

Nereida Sotelo

Role: primary

Other Identifiers

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2021-003672-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAAA601A52101

Identifier Type: -

Identifier Source: org_study_id