What side effects are associated with this type of intervention?

Common treatments for brain tumors similar to Lutathera (177Lu-DOTATATE) include peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues. Known side effects of these treatments can include hematologic toxicities such as myelodysplastic syndrome and acute myeloid leukemia, nephrotoxicity, and other treatment-related serious adverse events like respiratory tract infections. These side effects are generally rare but can be severe, necessitating careful patient selection and monitoring.

What prior FDA approvals exist?

The FDA has approved several treatments for brain tumors, though specific approvals for drugs targeting somatostatin receptors like Lutathera (177Lu-DOTATATE) are limited. Lutathera itself is approved for treating somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumors, and its use in brain tumors is currently under investigation. Other FDA-approved treatments for brain tumors include temozolomide, bevacizumab, and lomustine, which are used for high-grade gliomas and glioblastomas. These treatments, however, do not specifically target somatostatin receptors but rather work through different mechanisms such as alkylating DNA or inhibiting angiogenesis.

What other types of research exist?

Promising alternatives to Lutathera (177Lu-DOTATATE) for brain tumor patients include: 1) T-DXd (Trastuzumab deruxtecan), which has shown preliminary evidence of CNS activity in patients with brain metastases. 2) Tucatinib, capecitabine, and trastuzumab combination, which has demonstrated improved progression-free survival and overall survival in patients with HER2-positive metastatic breast cancer with brain metastases. 3) Regorafenib, a multitargeted kinase inhibitor, which has shown activity in advanced osteosarcoma and may have potential in brain tumors. These alternatives target different mechanisms but have shown promise in treating brain metastases or tumors.

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Radioisotope Therapy

Lutathera for Brain Tumor

Phase 1 & 2

Recruiting

Led By Margot Lazow

Research Sponsored by Ralph NULL Salloum

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have had their last fraction of craniospinal irradiation or total body irradiation or radiation to > 50% of pelvis > 3 months prior to enrollment, and focal irradiation > 4 weeks prior to enrollment

Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory

Must not have

Patients with any clinically significant unrelated systemic illness, serious infections, or significant cardiac, pulmonary, hepatic or other organ dysfunction

Patients who are receiving any other anti-cancer or investigational drug therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 8 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects of Lutathera include nausea, vomiting, fatigue, low blood counts leading to increased infection risk or bleeding problems, liver and kidney issues, hormonal imbalances due to pituitary damage, and rarely allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I received my last cancer treatment affecting my bone marrow 21 days ago, or 42 days ago if it was a specific type called nitrosourea.

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My tumor shows significant activity on a specific PET/CT scan.

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I have enough tumor samples for testing before the trial starts.

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My cancer has returned or worsened after standard treatment.

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My tumor shows SST2A expression.

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I am either 4-11 years old for Phase I or 12+ years old for Phase II.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any serious illnesses or organ problems.

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I am not currently on any cancer treatment or experimental drugs.

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I have been treated with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.

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My cancer has spread to my bone marrow.

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I have a history of cancer.

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I have had a condition where my lymphocytes grow abnormally.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 8 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 8 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 8 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assess PFS of Lutathera in CNS patients >12 years

Calculate the incidence of treatment related adverse events as assessed by CTCAE v5.0 in pediatric (4-12 yo) CNS patients treated with Lutathera

Estimate MTD of Lutathera in pediatric CNS patients 4-12 years

+1 more

Secondary study objectives

Calculate the incidence of treatment related adverse events as assessed by CTCAE v5.0 in CNS patients older than 12 yrs treated with Lutathera

Objective Response Rate of Lutathera in CNS patients >12 years

Other study objectives

Anti-tumor activity of Lutathera

Correlation of SST2A expression with clinical and molecular features in high-grade CNS tumor patients treated with Lutathera

Prevalence of SST2A expression in patients with different high-grade CNS tumors

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Phase I-IIExperimental Treatment1 Intervention

Pediatric patients (4 -12 years, Phase I) and adolescent and young adult patients (\>12years, 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 in this cohort 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.

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lutathera (177Lu-DOTATATE) works by targeting somatostatin receptors, which are often overexpressed in certain types of brain tumors, including high-grade CNS tumors and meningiomas. The drug binds to these receptors and delivers targeted radiation directly to the tumor cells, minimizing damage to surrounding healthy tissue. This targeted approach is crucial for brain tumor patients as it helps to reduce the side effects typically associated with conventional radiation therapy, thereby preserving neurological function and improving quality of life. Other common treatments for brain tumors, such as temozolomide and bevacizumab, work through different mechanisms like DNA damage and inhibition of blood vessel growth, respectively, but they also aim to maximize tumor control while minimizing harm to normal brain tissue.