Lutathera for Brain Tumor

Recruiting at8 trial locations

Overseen by Margot Lazow, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests Lutathera, a radioactive drug given through an IV, in patients with certain brain tumors that haven't responded to other treatments. The drug attaches to cancer cells and uses radiation to kill them.

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.

What data supports the effectiveness of the drug Lutathera for brain tumors?

Research shows that Lutathera (177Lu-DOTATATE) is effective in treating neuroendocrine tumors by targeting specific receptors on tumor cells. A pilot study suggests it may also be a viable option for high-grade gliomas (a type of brain tumor) that do not respond to standard treatments. ^{1 2 3 4 5}

Is Lutathera (Lutetium Lu 177 dotatate) safe for humans?

Lutathera has been used safely in treating certain types of tumors, with precautions to manage radiation exposure. However, it may cause side effects like potential damage to kidneys, liver, blood cells, and a risk of developing another cancer. ^{2 3 6 7 8}

How is the drug Lutathera unique for treating brain tumors?

Lutathera is unique because it is a targeted therapy that uses a radioactive substance to specifically target and bind to somatostatin receptors on tumor cells, which is different from traditional chemotherapy that affects both healthy and cancerous cells. This approach is already used for neuroendocrine tumors, and its application to brain tumors represents a novel use of this targeted treatment. ^{2 5 6 9 10}

Research Team

Margot Lazow, MD

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

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

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Lutathera (Radioisotope Therapy)

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.

Participant Groups

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 cycle.

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+

Catherine Krawczeski

Nationwide Children's Hospital

Chief Medical Officer

MD

Timothy C. Robinson

Nationwide Children's Hospital

Chief Executive Officer since 2019

BSc in Psychology and Business Administration from Indiana University

Ralph Salloum

Lead Sponsor

Trials

1

Recruited

70+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Steve Davis

Children's Hospital Medical Center, Cincinnati

Chief Executive Officer since 2021

MD

Daniel Ostlie

Children's Hospital Medical Center, Cincinnati

Chief Medical Officer

MD from University of North Dakota

Findings from Research

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 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]

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]

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]

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]

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 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 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]

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]

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]

References

1. France 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2023]

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

Feasibility and Therapeutic Potential of Peptide Receptor Radionuclide Therapy for High-Grade Gliomas. [2023]

5. England pubmed.ncbi.nlm.nih.gov

177Lu-Dotatate administration using an infusion pump or a peristaltic pump: comparison of two methods. [2022]

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

Radiation Safety Observations Associated with 177Lu Dotatate Patients. [2020]

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

Patient Release and Instructions for Lutetium Dotatate Radiopharmaceutical Therapy. [2023]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

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

Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

[68Ga-DOTATOC PET/CT for Diagnosing Neuroendocrine Tumors]. [2022]