Lu-DOTA-TATE + Standard Therapy for Glioblastoma

Recruiting at 20 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Bevacizumab

Disqualifiers: Active malignancy, Extensive leptomeningeal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 6 weeks for Group 1, 42 days for Group 3

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [177Lu]Lu-DOTA-TATE, a radiopharmaceutical therapy, for individuals with glioblastoma, an aggressive brain cancer. The goal is to determine the optimal dose when combined with standard treatments for newly diagnosed patients or as a standalone treatment for those with recurrent cancer. Suitable candidates have glioblastoma confirmed through tests and either have not started treatment or have experienced a recurrence after other treatments. This trial excludes those already receiving other active treatments for glioblastoma. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any additional active therapy for glioblastoma outside of the trial.

Is there any evidence suggesting that [177Lu]Lu-DOTA-TATE is likely to be safe for humans?

Research has shown that [177Lu]Lu-DOTA-TATE, a treatment under investigation for glioblastoma, has produced encouraging safety results. In studies involving patients with other tumors, such as meningiomas, the treatment was generally well-tolerated. It helped control the disease without causing serious side effects for most individuals.

Additionally, [177Lu]Lu-DOTA-TATE is already approved for certain neuroendocrine tumors, indicating a well-understood safety profile. While side effects may occur, they are usually manageable based on past experiences. However, individual reactions can vary, and this study aims to determine its safety specifically for glioblastoma patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Researchers are excited about [177Lu]Lu-DOTA-TATE for glioblastoma because it introduces a novel approach to treatment through targeted radiotherapy. Unlike standard treatments like surgery, radiotherapy, and chemotherapy with drugs such as Temozolomide, [177Lu]Lu-DOTA-TATE uses a radio-labeled compound that specifically targets tumor cells, potentially enhancing precision and minimizing damage to surrounding healthy tissue. This targeted mechanism could lead to improved outcomes and fewer side effects, offering a promising new option for patients with newly diagnosed or recurrent glioblastoma.

What evidence suggests that [177Lu]Lu-DOTA-TATE might be an effective treatment for glioblastoma?

Research shows that [177Lu]Lu-DOTA-TATE may be promising for treating glioblastoma, a type of brain tumor. In earlier studies with patients who had either newly diagnosed or returning glioma, treatment with [177Lu]Lu-DOTA-TATE resulted in 2 patients having no detectable tumor and 3 patients having smaller tumors out of 8 participants. This indicates that some tumors either disappeared or shrank significantly after treatment. In this trial, participants with newly diagnosed glioblastoma will receive [177Lu]Lu-DOTA-TATE in combination with standard therapy, while those with recurrent glioblastoma will receive [177Lu]Lu-DOTA-TATE as a single agent. The drug is already approved for treating certain other types of tumors, suggesting it might be effective for glioblastoma as well. Overall, these findings suggest it could help manage glioblastoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed glioblastoma, a type of brain cancer. They must have good bone marrow and organ function, and normal electrolyte levels. It's not open to those getting other active treatments for glioblastoma, with widespread leptomeningeal disease or another active cancer in the last 3 years.

Inclusion Criteria

My MRI shows a gadolinium-enhancing tumor.

My diagnosis is glioblastoma.

My blood, organs, and electrolyte levels are healthy.

Exclusion Criteria

I have had more than one treatment for my brain cancer.

I have not had radiopharmaceuticals recently or it's been long enough since my last dose.

I have not had any other cancer in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

1 visit (in-person)

Treatment

Participants receive [177Lu]Lu-DOTA-TATE in combination with radiotherapy and temozolomide for newly diagnosed glioblastoma, or as a single agent for recurrent glioblastoma

6 weeks for Group 1, 42 days for Group 3

Every 3-4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 8 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• [177Lu]Lu-DOTA-TATE
• [68Ga]Ga-DOTA-TATE

Trial Overview [177Lu]Lu-DOTA-TATE is being tested both as an add-on to standard care (radiotherapy and Temozolomide) for new glioblastoma patients and alone in those whose glioblastoma has come back. The study aims to find the right dose of [177Lu]Lu-DOTA-TATE.

How Is the Trial Designed?

Group I: Group 3 - Recurrent GB Experimental Treatment 2 Interventions

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

Group II: Group 1 - Newly diagnosed GB Experimental Treatment 4 Interventions

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)

[177Lu]Lu-DOTA-TATE is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults

Approved in United States as Lutathera for:

• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults
• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in children aged 12 years and older

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study involving five patients with progressive somatostatin receptor-positive disease, the radiolabelled somatostatin analogue [177Lu]Lu-DOTA-EB-TATE showed higher tumor doses compared to [177Lu]Lu-DOTA-TOC in 4 out of 5 patients, suggesting it may enhance therapeutic delivery to tumors.

However, while [177Lu]Lu-DOTA-EB-TATE delivered higher doses to tumors and critical organs like the kidneys and spleen, the tumor-to-critical organ dose ratios were better with [177Lu]Lu-DOTA-TOC in most cases, indicating that individual assessment is necessary to determine the best treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC. Hänscheid, H., Hartrampf, PE., Schirbel, A., et al.[2022]

177Lu-DOTA-Peptide 2, a new radioantagonist, showed high stability and selective binding to somatostatin receptors in HT-29 colorectal cancer cells, indicating its potential for targeted therapy.

The study demonstrated that 177Lu-DOTA-Peptide 2 has a low internalization rate and a high tumor uptake, making it a promising candidate for radionuclide therapy in treating somatostatin receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Behnammanesh, H., Erfani, M., Hajiramezanali, M., et al.[2023]

A study of 32 administrations of [177Lu]Lu-DOTA-TATE showed that using lead aprons significantly reduced radiation exposure for medical staff, with reductions of up to 71% for physicians and 68% for nurses.

The average radiation dose measured was consistent across different monitoring methods, indicating that with proper safety measures, administering [177Lu]Lu-DOTA-TATE can be done safely, although regular monitoring is essential to stay within annual dose limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. Riveira-Martin, M., Struelens, L., Muñoz Iglesias, J., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE is an effective treatment for inoperable neuroendocrine cancers that over-express somatostatin receptors, relying on the specific activity of the radiolabeled peptide to ensure therapeutic efficacy without receptor saturation.

Ongoing improvements in the purity and specific activity of 177Lu, as well as the reaction kinetics during the labeling process, can enhance the effectiveness of PRRT, allowing for better dose variations and optimization of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT. Breeman, WA., Chan, HS., de Zanger, RM., et al.[2019]

The study developed and validated a high-performance liquid chromatography (HPLC) method for quality control of the radiopeptide [177Lu]Lu-DOTA-TATE, ensuring its radiochemical purity meets therapeutic standards (95-105% of label claim).

The HPLC method demonstrated accuracy, precision, and sensitivity, making it suitable for clinical samples, which is crucial for the safe and effective use of [177Lu]Lu-DOTA-TATE in treating neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. van Andel, L., Aalbersberg, EA., Geluk-Jonker, MM., et al.[2021]

The study suggests that [(177)Lu]DOTA-TATE, a targeted radiotherapeutic, shows significantly higher internalization and tumor accumulation in medulloblastoma cells compared to the previously studied [(125)I]Gluc-TOCA, indicating its potential effectiveness in targeting this pediatric brain tumor.

[(177)Lu]DOTA-TATE demonstrated more favorable tumor-to-normal tissue ratios, which could lead to reduced toxicity and improved treatment outcomes for patients with medulloblastoma, making it a promising candidate for further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lu]-DOTA-Tyr-octreotate: A Potential Targeted Radiotherapeutic for the Treatment of Medulloblastoma. Vaidyanathan, G., Affleck, DJ., Zhao, XG., et al.[2022]

NCA-LuTATE, a radiolabeled peptide used for treating neuroendocrine tumors, has been administered safely in 39 injections across 13 patients, showing an acceptable radiation safety profile with an average kidney dose of 3.1 Gy per treatment cycle.

The study found that the clearance of NCA-LuTATE is influenced by the patient's kidney function, which is important for estimating radiation doses, and it produces less radioactive waste compared to traditional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. Bailey, DL., Hennessy, TM., Willowson, KP., et al.[2020]

The optimized protocol for preparing (177)Lu-DOTA-TATE allows for high specific activity and radiochemical purity, achieving a purity of 98.25% and specific activity ranging from 32.74 to 65.49 GBq/μmol across 100 batches prepared in India.

This method has successfully facilitated the administration of 250 patient doses to 150 individuals with inoperable neuroendocrine tumors, highlighting its potential efficacy as a treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of patient doses of (177)Lu-DOTA-TATE using indigenously produced (177)Lu: the Indian experience. Das, T., Chakraborty, S., Kallur, KG., et al.[2019]

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05109728

NCT05109728 | A Dose Finding Study of [177Lu]Lu-DOTA ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11631073/

Targeted radionuclide therapy for gliomas: Emerging clinical ... A subsequent study explored the efficacy of [177Lu]Lu-DOTATATE in 8 patients each with newly diagnosed or recurrent glioma and reported 2 complete and 3 partial ...

3. novartis.com novartis.com/clinicaltrials/study/nct05109728

A Dose Finding Study of [177Lu]Lu-DOTA-TATE in Newly ... 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 ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/08/07/jnumed.125.269633

[177Lu]Lu-DOTATATE for Recurrent Meningioma (LUMEN-1 ... [177Lu]Lu-DOTATATE is approved by the European Medicines Agency and the U.S. Food and Drug Administration for the treatment of SSTR2-positive ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10142322/

Lutathera® Orphans: State of the Art and Future Application of ... [177Lu]Lu-DOTATATE monotherapy protocol resulted in the highest 5-year OS (61.4%), despite tandem protocol ([90Y]Y-DOTATOC + [177Lu]Lu-DOTATATE) ...

6. lutathera-hcp.com lutathera-hcp.com/1l-netter-2-efficacy

1L: NETTER-2 | LUTATHERA® (lutetium Lu 177 dotatate) | HCP Review the efficacy of LUTATHERA® (lutetium Lu 177 dotatate) across the NETTER-2 clinical trials for 1L patients. See full Prescribing and Safety Information.