What side effects are associated with this type of intervention?

The most common treatments for Neuroendocrine Tumors (NETs) include Peptide Receptor Radionuclide Therapy (PRRT) with agents like Lutetium Lu 177 dotatate. Known side effects of PRRT include nausea, vomiting, fatigue, and mild to moderate hematologic toxicities such as thrombocytopenia, leukopenia, and anemia. Serious adverse events, though less common, can include myelodysplastic syndrome and renal toxicity. Other systemic therapies, such as everolimus, may cause stomatitis, infections, hyperglycemia, and non-infectious pneumonitis. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved Lutetium Lu 177 dotatate (177Lu-Dotatate) for the treatment of somatostatin-receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults. This approval was largely based on the NETTER-1 trial, which demonstrated its efficacy in controlling tumor growth and symptoms. Lutetium Lu 177 dotatate is a radioactive drug that delivers targeted radiation to tumor cells, reducing harm to normal cells. Other similar treatments include peptide receptor radionuclide therapy (PRRT) agents like 111In-octreotide, which have shown effectiveness in treating various types of neuroendocrine tumors by targeting somatostatin receptors.

What other types of research exist?

Promising novel alternatives to Lutetium Lu 177 dotatate for Neuroendocrine Tumors include: 1) Selpercatinib and Pralsetinib, which are selective RET inhibitors showing efficacy in RET-altered thyroid cancers; 2) Everolimus, an mTOR inhibitor used for progressive NETs; 3) Radiolabeled octreotide, which has shown efficacy in reducing calcitonin levels and extending survival in metastatic MTC; 4) Peptide receptor radionuclide therapy (PRRT) using other radiolabeled somatostatin analogs like Ga-68 DOTATATE, which is more sensitive for detecting small tumors. These alternatives offer targeted approaches and have demonstrated clinical benefits in recent studies.

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Radioactive Drug

Lutetium Lu 177 Dotatate for Lung Carcinoid Tumor

Phase 2

Recruiting

Led By Thomas A Hope

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

Confirmation of disease progression by RECIST v1.1 by real-time Alliance ICL at IROC Ohio central radiographic review

PRE-REGISTRATION: Recurrent or locally-advanced/unresectable or metastatic disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years from study registration

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the effect of lutetium Lu 177 dotatate in patients with advanced bronchial neuroendocrine tumors. Lutetium Lu 177 dotatate targets cancer cells with radiation, aiming to kill or shrink them while sparing healthy cells. The goal is to see if it works better than the usual treatment. Everolimus has been shown to help patients with various types of neuroendocrine tumors.

Who is the study for?

Adults with advanced bronchial neuroendocrine tumors that are well- or moderately-differentiated and have shown growth. They must not be pregnant, should have an ECOG performance status of 0-2, adequate organ function, no prior treatment with certain drugs like PRRT or mTOR inhibitors, and no active hepatitis B/C or other infections. Tumors must show somatostatin receptor positivity on specific PET scans.

What is being tested?

The trial is testing the effectiveness of Lutetium Lu 177 Dotatate compared to Everolimus in patients with advanced bronchial neuroendocrine tumors. It aims to see if this radioactive drug can better target tumor cells while sparing normal ones.

What are the potential side effects?

Possible side effects include nausea, vomiting, fatigue, blood cell count changes leading to increased infection risk or bleeding problems, liver toxicity which might affect its function and kidney damage due to radiation exposure.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has grown or spread as confirmed by a specific scan review.

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My cancer has returned, cannot be surgically removed, or has spread.

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I can take care of myself and perform daily activities.

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I don't have any other cancer needing treatment during the study, except for non-dangerous skin cancers or early-stage breast or cervical cancer.

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I am able to get out of my bed or chair and move around.

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My lung neuroendocrine tumor is confirmed to be well- or moderately-differentiated.

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My cancer has come back, cannot be surgically removed, or has spread.

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I am not allergic to everolimus or similar medications.

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My cancer is not a high-grade neuroendocrine or mixed tumor type.

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I had major surgery and fully healed at least 28 days ago.

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I have never been treated with mTOR inhibitors.

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My cancer is not a high-grade neuroendocrine or mixed tumor.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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My cancer originates from the lung's neuroendocrine cells.

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My cancer can be measured and is at least 1 cm in size, or 1.5 cm if it's in the lymph nodes.

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I can swallow normally and my stomach and intestines absorb medications as they should.

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I am 18 years old or older.

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I have never had PRRT treatment.

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My cancer can be measured on scans according to specific criteria.

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My lung tumor is a type of slow-growing cancer confirmed by a pathology report.

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I do not have liver cirrhosis.

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My pathology report identifies my tumor as a certain type of neuroendocrine or carcinoid tumor.

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My tumor is a well- or moderately-differentiated neuroendocrine type.

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My tumor is a low- or intermediate-grade neuroendocrine or carcinoid type.

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My cancer originates from the lung's neuroendocrine cells.

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I have never had lung inflammation from medication that needed treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years from study registration

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years from study registration

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years from study registration for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Median progression-free survival (PFS)

Secondary study objectives

Incidence of adverse events

Overall response rate (ORR)

Overall survival (OS)

Other study objectives

Incidence of late toxicities of lutetium Lu 177 dotatate therapy

Response rate

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm I (lutetium Lu 177 dotatate)Experimental Treatment6 Interventions

Patients receive lutetium Lu 177 dotatate IV over 30-40 minutes on day 1 of each cycle. Treatment repeats every 56 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET during screening. Patients also undergo CT or MRI during screening and on the trial as well as FDG PET and SPECT on the trial. Additionally, patients undergo blood and tissue sample collection during screening and on the trial.

Group II: Arm II (everolimus)Active Control6 Interventions

Patients receive everolimus PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may be able to cross-over to Arm I. Patients undergo PET during screening. Patients also undergo CT or MRI during screening and on the trial as well as FDG PET and SPECT on the trial. Additionally, patients undergo blood and tissue sample collection during screening and on the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Positron Emission Tomography

2011

Completed Phase 2

~2200

Single Photon Emission Computed Tomography

2008

Completed Phase 4

~320

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

0 / 26Eligibility 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

The most common treatments for Neuroendocrine Tumors (NETs) include somatostatin analogs, targeted therapies like everolimus, and peptide receptor radionuclide therapy (PRRT) such as Lutetium Lu 177 dotatate. Somatostatin analogs work by binding to somatostatin receptors on tumor cells, inhibiting hormone secretion and tumor growth. Everolimus targets the mTOR pathway, which is involved in cell growth and proliferation, thereby slowing tumor progression. PRRT, like Lutetium Lu 177 dotatate, delivers targeted radiation to tumor cells expressing somatostatin receptors, causing DNA damage and cell death. These mechanisms are crucial for NET patients as they offer targeted approaches to control tumor growth, manage symptoms, and potentially improve quality of life.