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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a drug called lutathera (Lutetium Lu 177 Dotatate) for treating meningiomas, a type of brain tumor that cannot be surgically removed and have worsened despite previous radiation treatment. Lutathera, a radioactive drug administered intravenously, specifically targets and aims to destroy tumor cells. The trial aims to determine if lutathera is both safe and effective for individuals whose meningiomas have continued to grow after radiation therapy. This study suits individuals whose meningiomas have grown by at least 15% over six months and have already received radiation treatment without the option for further radiotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

A previous study found Lutetium Lu 177 Dotatate (Lutathera) safe and effective for treating certain tumors, including meningiomas, a type of brain tumor. Research shows that patients generally tolerate this treatment well. In trials with individuals who had difficult-to-treat meningiomas, Lutathera worked without causing severe side effects.

Another study examined Lutathera in patients with central nervous system tumors and found similar safety results. Most participants did not experience major problems. However, like any treatment, some might have mild side effects, such as fatigue, nausea, or a drop in blood cell counts, which are common with many cancer treatments.

Overall, the available evidence supports Lutathera's safety for patients with specific types of progressive brain tumors. ^{1 2 3 4 5}

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

Unlike the standard treatments for progressive meningioma, which often involve surgery and radiation, Lutathera (lutetium Lu 177 dotatate) offers a novel approach by using targeted radiotherapy. This treatment specifically binds to somatostatin receptors prevalent on tumor cells, delivering radiation directly to the cancer cells while minimizing exposure to healthy tissue. Researchers are excited about Lutathera because this precision targeting could potentially enhance effectiveness while reducing side effects, providing a promising alternative for patients with progressive meningioma.

What evidence suggests that Lutathera might be an effective treatment for progressive meningioma?

Research has shown that lutetium Lu 177 dotatate, or Lutathera, may help treat meningiomas, which are tumors in the brain or spinal cord. Studies have found that this drug targets and kills tumor cells by delivering radiation directly to them. In this trial, patients will receive Lutathera, which has shown positive results in those whose meningiomas did not respond to other treatments. Almost all meningiomas have special sites called somatostatin receptors, and Lutathera attaches to these sites to deliver focused radiation. This targeted method has effectively slowed tumor growth and improved patient outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Kenneth W. Merrell, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12528330/

Efficacy of Intra-arterial [177Lu]Lu-DOTATATE monotherapy ... In a treatment-refractory meningioma cohort, intra-arterial administration of [177Lu]Lu-DOTATATE is safe and effective, with an objective ...

2. redjournal.org redjournal.org/article/S0360-3016(24)00765-X/fulltext

A Prospective, Phase II Study of 177Lu-Dotatate in Patients ... As nearly all meningiomas express somatostatin receptors, we evaluated the efficacy of lutetium-177 ( 177 Lu)–Dotatate for refractory meningioma.

3. 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, ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20467879

A Study of Lutetium Lu 177 Dotatate (Lutathera®) in ... The purpose of this study is to estimate the efficacy of LUTATHERA treatment in patients with recurrent grade 1 meningioma as measured by 6-month PFS rate.

5. 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 ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04082520/

Clinical Trial: NCT04082520 The goal of this study is to determine whether this drug is safe and effective in treating meningiomas that progress after radiation treatment.