Lutathera for Brain Tumor

Recruiting at 7 trial locations

Overseen By Kelsey H Troyer, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ralph NULL Salloum

Must not be taking: Anti-cancer drugs

Disqualifiers: Bone marrow metastasis, Bulky disease, Breast-feeding, Type I diabetes, 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: 1

Duration: 8 months

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called Lutathera to determine its safety and effectiveness for people with certain aggressive brain tumors that have recurred or worsened. Lutathera is administered through an IV every eight weeks for up to four doses. The trial seeks participants with high-grade CNS tumors or meningiomas that have been previously treated but continue to grow or have returned. Eligible participants must have undergone prior treatment and require a special scan (DOTATATE PET) to confirm the tumor's ability to absorb Lutathera. This trial targets children, teens, and young adults aged 4 to 39 years. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You must be off long-acting somatostatin analogs for at least 4 weeks and short-acting ones for at least 24 hours. Additionally, you cannot be on any other anti-cancer or investigational drug therapy.

Is there any evidence suggesting that Lutathera is likely to be safe for humans?

Research has shown that Lutathera (177Lu-DOTATATE) is usually well-tolerated. In earlier studies, patients experienced few side effects. Common issues such as headaches and dizziness occurred in about 17% of participants, while serious reactions were rare. The FDA has approved Lutathera for certain types of tumors, indicating a good safety record for those conditions. This suggests it might be safe for the brain tumors under study, although further research is needed to confirm this. ^{1 2 3 4 5}

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

Unlike the standard treatments for brain tumors, which typically involve surgery, radiation, and chemotherapy, Lutathera offers a targeted approach. Lutathera is a radiopharmaceutical that specifically targets tumors expressing the SST2A receptor, delivering radiation directly to cancer cells and sparing more healthy tissue. Researchers are excited about Lutathera because it could provide a more precise treatment option with potentially fewer side effects, and it holds promise in slowing tumor progression in a shorter timeframe. This innovative mechanism of action differentiates it from conventional therapies and offers hope for improved outcomes in patients with high-grade central nervous system tumors and meningiomas.

What evidence suggests that Lutathera might be an effective treatment for brain tumors?

Research has shown that Lutathera, also known as 177Lu-DOTATATE, might help treat certain brain tumors. In this trial, pediatric patients and adolescent and young adult patients with recurrent or progressive high-grade central nervous system tumors and meningiomas will receive Lutathera. Studies have found that this treatment can help patients live longer without their disease worsening. In past cases, Lutathera treated patients with recurring or hard-to-treat tumors and showed promise in managing these conditions. The treatment is generally well-tolerated, meaning most patients can handle it without serious side effects. Overall, these findings suggest that Lutathera could be a hopeful option for treating certain challenging brain tumors. ^{2 4 5 6 7}

Who Is on the Research Team?

Margot Lazow, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults with high-grade brain tumors or meningiomas that have gotten worse or come back after treatment. They must be stable neurologically, not on certain cancer drugs, and their tumors should show a specific protein (SST2A) and take up a special dye on PET scans. Ages 4-12 are in Phase I, while those older than 12 are in Phase II.

Inclusion Criteria

I had major radiation therapy more than 3 months ago, or targeted radiation over 4 weeks ago.

Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control while being treated on this study and for a specified period after drug cessation

I have a high-grade brain tumor or meningioma that is not responding to treatment.

Exclusion Criteria

You have type I diabetes.

I do not have any serious illnesses or organ problems.

Patients with large tumors as seen on imaging.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lutathera intravenously once every 8 weeks for up to 4 doses over 8 months

8 months

1 visit every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lutathera

Trial Overview The study tests Lutathera (177Lu-DOTATATE), given through the vein every 8 weeks for up to four doses over eight months. It aims to see if it's safe and works well against these brain tumors/meningiomas that absorb a particular diagnostic dye indicating they may respond to this therapy.

How Is the Trial Designed?

Group I: Phase I-II Experimental Treatment 1 Intervention

Pediatric patients (4 to \<12 years, Phase I) and adolescent and young adult patients (12 to \</=39 years, Phase II) with recurrent/progressive high-grade central nervous system tumors and meningiomas that express SST2A and demonstrate uptake on DOTATATE PET will receive Lutathera once every 8 weeks (1 cycle) for a total of 4 doses over 8 months Phase I starting dose will be 200 mCi\*(BSA/1.73m2), corresponding to the BSA-adjusted FDA approved adult Lutathera dosing. The first cycle will be used as the DLT period. Once MTD/RP2D is established, an efficacy expansion cohort of up to 10 patients will be opened to determine the preliminary efficacy of MTD/RP2D of Lutathera Phase II patients will receive the adult RP2D of 200 mCi every 8 weeks to determine the anti-tumor activity of Lutathera in this patient population, through evaluation of 6-month PFS as the primary efficacy endpoint. Response will be assessed on imaging (brain/spine MRI and DOTATATE PET) following every 1-2 cycles.

Lutathera is already approved in United States, European Union for the following indications:

Approved in United States as Lutathera for:

• Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults and pediatric patients 12 years and older

Approved in European Union as Lutathera for:

• Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults

Who Is Running the Clinical Trial?

Ralph NULL Salloum

Lead Sponsor

Trials

1

Recruited

70+

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Ralph Salloum

Lead Sponsor

Trials

1

Recruited

70+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

In a study of 219 Lutathera injections over 70 months, using a peristaltic pump (method 2) resulted in a 34.9% reduction in residual radioactivity compared to a volumetric infusion pump (method 1), indicating improved efficiency in drug delivery.

Despite method 2 having a higher cost per injection, it was reported to be safer and more suitable by operators, with no major incidents occurring during its use, suggesting it may be a better option for future radioligand therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods. Donzé, C., Rubira, L., Santoro, L., et al.[2022]

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 successfully demonstrated that pharmacokinetic parameters of Lu-177 DOTATATE can be derived from SPECT/CT imaging, allowing for non-invasive monitoring of drug distribution in patients with neuroendocrine tumors.

The findings revealed significant differences in drug clearance and distribution between blood and bone marrow, suggesting that individual patient characteristics, such as weight, can be used to optimize personalized dosing strategies for improved treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Lu-177 DOTATATE (Lutathera&#174;) Case. Barakat, A., Santoro, L., Vivien, M., et al.[2023]

In a study of 38 patients with stage IV neuroendocrine tumors, lutetium-177 (177Lu)-DOTATATE therapy significantly improved global health-related quality of life from the start of treatment to three months after completion.

Patients reported notable reductions in nausea, vomiting, and gastrointestinal symptoms, indicating that 177Lu-DOTATATE therapy not only enhances overall well-being but also alleviates specific disease-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Cohort Real-World Study on Neuroendocrine Tumor Patient's Quality of Life During Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE. Ramim, JE., Matheos de Lima, BA., Bulzico, DA., et al.[2023]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

In a pilot study involving 16 patients with high-grade gliomas (HGGs) that were inoperable or resistant to standard treatments, 177Lu-DOTATATE showed potential therapeutic effects, with 12.5% achieving complete remission and 31.25% showing partial remission.

Despite some positive treatment responses, overall quality of life scores did not significantly improve, indicating that while 177Lu-DOTATATE may be beneficial, further research is needed in a more targeted patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Therapeutic Potential of Peptide Receptor Radionuclide Therapy for High-Grade Gliomas. Nemati, R., Shooli, H., Rekabpour, SJ., et al.[2023]

Lutathera, approved in Japan in 2021, is the first peptide receptor radionuclide therapy specifically designed for treating somatostatin receptor-positive neuroendocrine tumors, providing a much-needed treatment option for these patients.

Current imaging methods in Japan for assessing somatostatin receptor expression in tumors primarily rely on In-111 pentetreotide scintigraphy, but advancements like 68Ga-DOTA-SSA PET/CT are being explored to improve evaluation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[68Ga-DOTATOC PET/CT for Diagnosing Neuroendocrine Tumors]. Koyasu, S., Shimizu, Y., Nakamoto, Y.[2022]

Lutetium Dotatate (Lutathera) is an FDA-approved radiopharmaceutical therapy for treating somatostatin receptor positive neuroendocrine tumors, allowing for effective outpatient treatment.

The study confirms that Lutathera can be safely administered on an outpatient basis, provided that patients are informed about safety measures and travel restrictions related to radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Release and Instructions for Lutetium Dotatate Radiopharmaceutical Therapy. Underwood, J., Sturchio, G., Arnold, S.[2023]

Lutetium-177 dotatate (Lutathera®) is an effective outpatient treatment for neuroendocrine tumors, administered in four cycles of 7.4 GBq each, with minimal radiation exposure to staff and surrounding areas when proper safety protocols are followed.

The treatment can be safely conducted in standard hospital procedural rooms without the need for extra shielding, provided that precautions are taken to manage radiation exposure and contamination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Safety Observations Associated with 177Lu Dotatate Patients. Nelson, KL., Sheetz, MA.[2020]

Lutetium Lu 177 dotatate (Lutathera®) is an approved targeted therapy specifically for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), offering a new treatment option for this heterogeneous group of tumors.

Patients who are already receiving octreotide long-acting release may be eligible for this second-line therapy, highlighting the importance of personalized treatment plans in managing advanced NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. Boucher, JE., Sommers, R.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05278208

Lutathera for Treatment of Recurrent or Progressive High ... This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7930777/

Efficacy of 177Lu-Dotatate Therapy in the Treatment of ... Lutetium Lu 177 dotatate was administered intravenously at a dose of 200 mCi per dose every 8 weeks for 4 cycles. Treatment was tolerated very well, with no ...

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

[177Lu]Lu-DOTATATE for Recurrent Meningioma (LUMEN-1 ... CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2017–2021. Neuro Oncol ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05352

Lutathera for the Treatment of Patients with Recurrent ... Lutathera may be safe, tolerable, and/or effective in treating patients with recurrent, progressive or refractory CNS tumors and meningiomas.

5. newsnetwork.mayoclinic.org newsnetwork.mayoclinic.org/discussion/radiopharmaceutical-therapy-shows-favorable-results-for-people-with-tough-to-treat-meningioma-brain-tumors-mayo-clinic-study-finds/

Radiopharmaceutical therapy shows favorable results for ... Phase 2 clinical trial finds 177 Lu-Dotatate may extend progression-free survival for patients with no other options to manage recurrent disease.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208700s031lbl.pdf

LUTATHERA® (lutetium Lu 177 dotatate) injection, for ... The safety data of LUTATHERA with octreotide was evaluated in NETTER-1 [see ... Nervous system disorders. Headache. 17. 0. 5. 0. Dizziness. 17. 0. 8. 0. Dysgeusia.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04082520

Study Details | NCT04082520 | Lutathera for the Treatment ... This phase II trial studies how well lutathera works in treating patients with meningioma that cannot be treated with surgery (inoperable) and is growing, ...