Last Update: Aug 02, 2024
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
ClinicalTrials.gov Identifier:
Novartis Reference Number:CAAA601A52101
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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 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.

Glioblastoma
Phase1
Recruiting
60
May 10, 2022
Aug 10, 2026
All
18 Years - (Adult, Older Adult)

Interventions

Other

Radiotherapy

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

Eligibility 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 (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

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