What side effects are associated with this type of intervention?

Lutetium Lu 177 Dotatate, a targeted radiation therapy, is generally well-tolerated but can cause side effects such as mild to moderate renal impairment, myelodysplastic syndrome, and, rarely, acute myeloid leukemia. Common side effects also include nausea, vomiting, and fatigue. Enzyme inhibitors like Peposertib, which block enzymes necessary for tumor cell growth, may cause side effects including gastrointestinal disturbances, fatigue, and potential hematologic toxicities. Combining these therapies aims to enhance efficacy but may also increase the risk of compounded side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for neuroendocrine tumors (NETs) that involve enzyme inhibition and targeted radiation. Lutetium Lu 177 Dotatate (Lutathera) is a notable FDA-approved targeted radiotherapy for NETs, which delivers radiation directly to tumor cells expressing somatostatin receptors. Additionally, enzyme inhibitors like everolimus (Afinitor) have been approved for treating certain types of NETs by inhibiting the mTOR pathway, which is crucial for cell growth and proliferation. These treatments represent significant advancements in the management of NETs, offering targeted approaches to control tumor growth and symptoms.

What other types of research exist?

Promising alternatives for treating neuroendocrine tumors in 2024 include: 1) Everolimus, an mTOR inhibitor, which has shown efficacy in progressive NETs. 2) Radiolabeled somatostatin analogs like 64Cu-DOTATATE for PET/CT imaging and potential therapeutic use. 3) Selective RET inhibitors such as Selpercatinib and Pralsetinib for RET-altered NETs. 4) Peptide receptor radionuclide therapy (PRRT) using agents like 177Lu-DOTA-cetuximab, which targets EGFR and has shown favorable tumor targeting efficacy.

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Radioactive Drug

Peposertib + Radiation Therapy for Pancreatic Cancer

Phase 1

Waitlist Available

Led By Lowell Anthony

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Age >= 18 years

Failure of at least one prior systemic cancer treatment with somatostatin analogs

Must not have

Discontinue long-acting somatostatin analogs for at least 4 weeks prior to initiating lutetium Lu 177 dotatate

Patients with an inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months post-treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the combination of peposertib and lutetium Lu 177 dotatate in patients with neuroendocrine tumors. Peposertib blocks enzymes needed for tumor growth, while lutetium Lu 177 dotatate targets and kills tumor cells with radiation. Lutetium Lu 177 dotatate has been used to treat inoperable neuroendocrine tumors and has shown to improve patients' quality of life. The goal is to find the best dose and observe potential benefits and side effects.

Who is the study for?

Adults with well-differentiated pancreatic neuroendocrine tumors, who've had a positive dotatate scan and failed at least one cancer treatment. They must have good organ function, no prior radionuclide therapy, be able to swallow pills, not pregnant or breastfeeding, and without serious infections or psychiatric issues that could affect participation.

What is being tested?

The trial is testing the combination of M3814 (Peposertib) with Lutetium Lu 177 Dotatate radiation therapy to determine the best dose and assess potential benefits and side effects in treating neuroendocrine tumors. Peposertib blocks enzymes needed for cell growth while the radioactive drug targets tumor cells.

What are the potential side effects?

Possible side effects include reactions related to blocking cell growth enzymes by peposertib which might affect normal cellular functions, as well as radiation-related effects from Lutetium Lu 177 Dotatate that may cause damage to both tumor and potentially some normal cells.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I have tried a cancer treatment involving somatostatin analogs without success.

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I have never had peptide receptor radionuclide therapy.

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I have chronic hepatitis B but it's under control with medication.

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I will avoid pregnancy or fathering a child for the required period after my last lutetium treatment.

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I can take care of myself but might not be able to do heavy physical work.

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I had hepatitis C but am now cured or currently being treated with an undetectable viral load.

Exclusion Criteria

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

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I have stopped taking long-acting somatostatin analogs for 4 weeks.

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I cannot swallow pills or have a condition that affects how my body absorbs medication.

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I have not had major surgery in the last 4 weeks.

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I have received PRRT-based treatments before.

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I have not had a live vaccine or an active infection in the last 4 weeks.

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I do not have any unmanaged ongoing illnesses.

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I am allergic to certain cancer drugs similar to M3814 or lutetium Lu 177 dotatate.

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I cannot stop taking my acid reflux medication.

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I have had extensive radiation therapy affecting most of my bone marrow.

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I cannot stop taking certain medications or supplements that affect my liver enzymes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months post-treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose limiting toxicity

Secondary study objectives

Overall response rate

Overall survival

Progression free survival

Other study objectives

Krenning score from the gallium 68 or copper 64 dotatate

Pharmacokinetic (PK) analysis

Radiographic expression of somatostatin receptors

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: Treatment (peposertib, lutetium Lu 177 dotatate)Experimental Treatment5 Interventions

Patients receive peposertib PO QD or BID on days 1-21 and lutetium Lu 177 dotatate IV over 30 minutes on day 1. Treatment repeats every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/MRI throughout the trial and undergo collection of blood samples on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Computed Tomography

2017

Completed Phase 2

~2790

Biospecimen Collection

2004

Completed Phase 3

~2030

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Peposertib

2021

Completed Phase 1

~20

0 / 17Eligibility 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

Neuroendocrine Tumors (NETs) are often treated using targeted therapies that exploit specific characteristics of the tumor cells. Lutetium Lu 177 Dotatate is a form of peptide receptor radionuclide therapy (PRRT) that delivers targeted radiation to tumor cells expressing somatostatin receptors, thereby minimizing damage to surrounding healthy tissue. This targeted approach is crucial for reducing side effects and improving treatment efficacy. Peposertib, an enzyme inhibitor, works by blocking enzymes necessary for tumor cell growth and survival, thereby inhibiting tumor progression. Combining these therapies can potentially enhance treatment outcomes by simultaneously attacking the tumor through different mechanisms, offering a more comprehensive approach to managing NETs.

Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours.