Lu-DOTA-TATE + Standard Therapy for Glioblastoma

Recruiting at 21 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

Trial Summary

What is the purpose of this trial?

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

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.

What data supports the effectiveness of the drug Lu-DOTA-TATE for treating glioblastoma?

Research shows that Lu-DOTA-TATE, a drug used in peptide receptor radionuclide therapy (PRRT), has been effective in treating neuroendocrine tumors by targeting somatostatin receptors. Additionally, studies suggest its potential in treating medulloblastoma, a type of brain tumor, due to its ability to accumulate in tumors and spare normal tissues, indicating it may also be promising for glioblastoma treatment. ^{1 2 3 4 5}

Is Lu-DOTA-TATE generally safe for humans?

Lu-DOTA-TATE has been used as a treatment for neuroendocrine tumors, and studies have focused on its early efficacy and toxicity. While specific safety data for glioblastoma is not available, it has been administered since 2012 for other conditions, suggesting some level of established safety in humans. ^{2 4 6 7 8}

What makes the drug Lu-DOTA-TATE unique for treating glioblastoma?

Lu-DOTA-TATE is unique because it is a targeted radiotherapy that uses a radioactive substance to specifically bind to somatostatin receptors, which are often overexpressed in certain tumors. This allows for direct delivery of radiation to cancer cells, potentially reducing damage to surrounding healthy tissue compared to conventional treatments. ^{1 2 4 7 9}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

[Lu]-DOTA-Tyr-octreotate: A Potential Targeted Radiotherapeutic for the Treatment of Medulloblastoma. [2022]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT. [2019]

3. Iran pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Preparation of patient doses of (177)Lu-DOTA-TATE using indigenously produced (177)Lu: the Indian experience. [2019]

5. Iran pubmed.ncbi.nlm.nih.gov

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]

7. Netherlands 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. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Intraindividual comparison of [177Lu]Lu-DOTA-EB-TATE and [177Lu]Lu-DOTA-TOC. [2022]