Lutathera for Progressive Meningioma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Octreotide

Disqualifiers: Pregnancy, HIV, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 7

Duration: 32 weeks

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well Lutathera works in treating patients with meningioma that cannot be treated with surgery and is getting worse after radiation therapy. Lutathera is a radioactive drug that targets and kills tumor cells. The goal is to see if it is safe and effective for these patients.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on somatostatin LAR or short-acting octreotide, you may need to stop these before treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Lutathera for progressive meningioma?

Research shows that Lutathera (Lutetium Lu 177 Dotatate) can help stabilize tumor growth in some patients with progressive meningioma, especially those with certain types of tumors that have specific receptors (somatostatin receptors). In one study, 85.7% of patients with a certain type of meningioma (WHO grade II) did not see their tumors grow for at least six months after treatment. ^{1 2 3 4 5}

Is Lutathera safe for treating meningioma?

Lutathera (Lutetium Lu 177 Dotatate) has been used safely in patients with meningiomas and other tumors, with studies showing it is generally well tolerated without notable adverse events. Radiation safety measures are important during treatment to minimize exposure, but it can be safely administered in a hospital setting. ^{1 2 4 6 7}

How does the drug Lutathera differ from other treatments for progressive meningioma?

Lutathera is unique because it uses a radioactive substance, Lutetium Lu 177, to target and destroy cancer cells, which is different from traditional treatments like surgery or chemotherapy that do not use radioactivity. This approach is novel for progressive meningioma, as there are no standard treatments specifically for this condition. ^{8 9 10 11 12}

Research Team

Kenneth W. Merrell, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with inoperable, progressive meningioma after radiation therapy. They must have had prior treatments like surgery if possible, show tumor growth on scans, and not be candidates for more radiotherapy. Participants need to have a certain level of physical fitness (ECOG PS <=2), adequate organ function, and agree to use contraception if applicable.

Inclusion Criteria

Your hemoglobin level should be at least 9.0 grams per deciliter.

You have a disease that can be measured or seen by the doctor.

I agree to a 68Ga-DOTATATE PET scan and my scan shows a Krenning score of 2 or higher.

Exclusion Criteria

I am not on any experimental drugs for my cancer.

I have a tumor in the covering of my optic nerve or outside my brain.

I am of childbearing age and do not plan to use birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lutetium Lu 177 dotatate IV over 30-40 minutes every 8 weeks for up to 4 cycles

32 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for 2 years, then every 6 months

Treatment Details

Interventions

• Lutetium Lu 177 Dotatate

Trial Overview The trial tests Lutathera's effectiveness and safety in treating meningiomas that worsen post-radiation. It involves radioactive drug infusion targeting cancer cells, alongside assessments through questionnaires, quality-of-life measures, MRI scans, and PET imaging using Gallium Ga 68-DOTATATE.

Participant Groups

Group I: Treatment (gallium Ga 68-DOTATATE PET/MRI, Lutathera) Experimental Treatment 8 Interventions

Patients receive gallium Ga 68-DOTATATE IV and undergo a PET/MRI or PET/CT before cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI on study and during follow-up, as well as blood sample collection and possible SEPCT/CT dosimetry on study.

Lutetium Lu 177 Dotatate is already approved in European Union, United States for the following indications:

Approved in European Union as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Approved in United States as Lutathera for:

• Gastroenteropancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A 62-year-old man with recurrent anaplastic meningioma showed significant tumor progression despite previous treatments, but was treated with Lutetium Lu 177 dotatate, which was well-tolerated with no notable adverse events.

After initial tumor growth following the first treatment cycle, the tumor volume stabilized and showed a decrease after the second cycle, indicating potential efficacy of Lutetium Lu 177 dotatate in managing this aggressive tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of 177Lu-Dotatate Therapy in the Treatment of Recurrent Meningioma. Zahid, A., Johnson, DR., Kizilbash, SH.[2022]

In a study of 8 patients with recurrent WHO grade II meningiomas treated with 177Lu-DOTATATE, the progression-free survival at 6 months (PFS-6) was an impressive 85.7%, indicating that this treatment can be effective for refractory cases.

When compared to other studies, SSTR-targeted peptide receptor radionuclide therapy (PRRT) showed a PFS-6 of 89.7% for WHO grade I meningiomas and 57.1% for WHO grade II, suggesting that while effective for lower-grade tumors, it may not be suitable for the most aggressive forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatostatin Receptor Theranostics for Refractory Meningiomas. Salgues, B., Graillon, T., Horowitz, T., et al.[2022]

In a phase II clinical study involving 14 patients with progressive meningiomas, treatment with the radiopharmaceutical 177Lu-DOTATATE was well tolerated, with 50% of patients achieving progression-free survival at 6 months.

The study demonstrated that 68Ga-DOTATATE PET imaging could effectively assess treatment response, showing significant reductions in tumor uptake and size in some patients, indicating potential therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the SSTR2-targeted radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as imaging biomarker in patients with intracranial meningioma. Kurz, SC., Zan, E., Cordova, C., et al.[2023]

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 seven patients with progressive meningioma treated with 177Lu-DOTATATE, the therapy showed variable effectiveness, with a 42.9% progression-free survival rate at six months.

The study highlights the importance of using PET-based volumetric imaging alongside traditional MRI for better response assessment in peptide receptor radionuclide therapy (PRRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response assessment of somatostatin receptor targeted radioligand therapies for progressive intracranial meningioma. Müther, M., Roll, W., Brokinkel, B., 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]

In a study of 20 patients with meningiomas, [68Ga]-DOTATATE PET/MRI successfully confirmed recurrent tumors in 85% of cases, demonstrating its effectiveness in distinguishing between tumor recurrence and post-treatment changes.

The novel quantitative analysis approach used in this study showed a significant difference in uptake values between meningiomas and post-treatment changes, suggesting that [68Ga]-DOTATATE PET/MRI could enhance diagnostic accuracy and treatment planning for meningioma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gallium-68 DOTATATE PET in the Evaluation of Intracranial Meningiomas. Ivanidze, J., Roytman, M., Lin, E., et al.[2020]

In a study involving six children with central precocious puberty due to neurofibromatosis and/or optic gliomas, treatment with the LHRH analogue D-Trp6-Pro9-NEt-LHRH effectively suppressed hormone levels and stabilized or regressed secondary sexual characteristics over six months.

The therapy also resulted in decreased growth velocity and slowed bone age maturation, indicating its efficacy in managing precocious puberty in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precocious puberty associated with neurofibromatosis and optic gliomas. Treatment with luteinizing hormone releasing hormone analogue. Laue, L., Comite, F., Hench, K., et al.[2019]

In a study of 25 patients with optico-hypothalamic gliomas treated with radiation therapy, the 10-year overall survival rate was 94%, and the progression-free survival rate was 69%, indicating that radiation is an effective treatment for managing these tumors.

Younger patients (under 10 years) were more likely to experience hypothalamic-pituitary deficiencies compared to older patients, highlighting the importance of age in treatment outcomes and the need for long-term monitoring for hormonal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy of optico-hypothalamic gliomas (OHG)--radiographic response, vision and late toxicity. Grabenbauer, GG., Schuchardt, U., Buchfelder, M., et al.[2019]

In a 17-year study of 18 children with optic pathway/hypothalamic gliomas, treatment methods including surgery, chemotherapy, and radiotherapy resulted in tumor shrinkage and stabilization, but none completely eradicated the tumors.

The study reported an 80% overall survival rate and a 63.3% progression-free survival rate over five years, highlighting the effectiveness of chemotherapy as a primary treatment for progressive cases, despite significant long-term endocrine complications in over half of the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of optic pathway hypothalamic gliomas in childhood: experience with 18 consecutive cases. Jaing, TH., Lin, KL., Tsay, PK., et al.[2011]

Radiation therapy (RT) is effective for treating pediatric optic pathway or hypothalamic low-grade gliomas, with a 10-year event-free survival rate of 67.5% for patients without neurofibromatosis type 1 (NF-1).

The study, which followed 89 patients for a median of 12.5 years, found that older children without NF-1 had a low risk of late toxicity from RT, suggesting it can be safely considered for younger patients or those with NF-1 as a salvage treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy for Optic Pathway and Hypothalamic Low-Grade Gliomas in Children. Tsang, DS., Murphy, ES., Merchant, TE.[2018]

In a review of 24 children with symptomatic gliomas involving the optic chiasm, definitive radiation therapy resulted in an impressive 88% rate of freedom from disease progression and a 100% overall survival rate over a median follow-up of 6 years.

While radiation therapy effectively controlled tumor growth and led to visual improvement or stabilization in 91% of patients, it also resulted in significant endocrine issues, particularly growth hormone deficiency in 15 out of 18 evaluated patients, highlighting the need for careful monitoring and management of long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects. Pierce, SM., Barnes, PD., Loeffler, JS., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of 177Lu-Dotatate Therapy in the Treatment of Recurrent Meningioma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Somatostatin Receptor Theranostics for Refractory Meningiomas. [2022]

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

Evaluation of the SSTR2-targeted radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as imaging biomarker in patients with intracranial meningioma. [2023]

4. Iran pubmed.ncbi.nlm.nih.gov

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

5. Germany pubmed.ncbi.nlm.nih.gov

Response assessment of somatostatin receptor targeted radioligand therapies for progressive intracranial meningioma. [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

Gallium-68 DOTATATE PET in the Evaluation of Intracranial Meningiomas. [2020]

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

Precocious puberty associated with neurofibromatosis and optic gliomas. Treatment with luteinizing hormone releasing hormone analogue. [2019]

9. Ireland pubmed.ncbi.nlm.nih.gov

Radiation therapy of optico-hypothalamic gliomas (OHG)--radiographic response, vision and late toxicity. [2019]

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

Treatment of optic pathway hypothalamic gliomas in childhood: experience with 18 consecutive cases. [2011]

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

Radiation Therapy for Optic Pathway and Hypothalamic Low-Grade Gliomas in Children. [2018]

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

Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects. [2019]