Lutetium Lu 177 Dotatate for Lung Carcinoid Tumor

Recruiting at 31 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Somatostatin analogs

Must not be taking: P-gp inhibitors, CYP3A4 inducers

Disqualifiers: High-grade carcinoma, CNS metastases, 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: 3

Duration: 8 months for lutetium Lu 177 dotatate, ongoing for everolimus

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lutetium Lu 177 dotatate for individuals with advanced lung carcinoid tumors, a rare type of lung cancer. The goal is to determine if this radioactive drug, which attaches to certain tumor cells and releases radiation to kill them, is more effective than the usual treatment, everolimus. Participants should have lung carcinoid tumors that have spread and shown signs of worsening in the past year. This trial might be suitable for those in this situation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does require stopping P-gp and strong CYP3A4 inhibitors and/or inducers 7 days before registration. You can continue somatostatin analogs if you have functional tumors and have shown disease progression on them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lutetium Lu 177 dotatate is generally safe for people. In one study, patients with advanced lung neuroendocrine tumors who received this treatment found it well-tolerated. Most side effects were mild, such as nausea, vomiting, and tiredness, while serious side effects were less common. This treatment has also been used in patients with similar tumors, known as somatostatin receptor-positive tumors, and has demonstrated a good safety record, indicating a lower likelihood of harmful side effects. Overall, lutetium Lu 177 dotatate appears to be a safe option for those considering participation in this clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung carcinoid tumors?

Unlike the standard treatments for lung carcinoid tumors, which typically include surgery, chemotherapy, or targeted therapies like everolimus, Lutetium Lu 177 Dotatate is a targeted radiotherapy. This treatment is unique because it uses a radioactive isotope, Lutetium-177, attached to a molecule that seeks out tumor cells, delivering radiation directly to them and minimizing damage to healthy tissue. Researchers are excited about Lutetium Lu 177 Dotatate because it offers a novel approach by combining precision targeting with the therapeutic effects of radiation, potentially leading to more effective treatment with fewer side effects. Additionally, patients with disease progression on everolimus can cross over to receive Lutetium Lu 177 Dotatate, offering a new avenue of hope for those not responding to existing therapies.

What evidence suggests that lutetium Lu 177 dotatate might be an effective treatment for lung carcinoid tumors?

Research has shown that lutetium Lu 177 dotatate, which participants in this trial may receive, can help treat advanced neuroendocrine tumors, including those in the lungs. In earlier studies, about 17% of patients experienced partial tumor shrinkage, and many others maintained stable disease without progression. Patients who received lutetium Lu 177 dotatate typically went about three years without cancer worsening. This treatment is also associated with longer survival times compared to some other treatments. In this trial, researchers will compare lutetium Lu 177 dotatate to everolimus, another treatment option, to evaluate its effectiveness in managing these tumors. ^{3 5 6 7 8}

Who Is on the Research Team?

Thomas A Hope

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

Your medical history includes information about the type of cancer you have from either the original or secondary site.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for imaging and sample collection

Treatment

Participants receive either lutetium Lu 177 dotatate or everolimus. Lutetium Lu 177 dotatate is administered IV every 56 days for 4 cycles, while everolimus is taken orally daily in 28-day cycles.

8 months for lutetium Lu 177 dotatate, ongoing for everolimus

Regular visits for imaging and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months until disease progression and then every 6 months for up to 5 years.

Up to 5 years

Follow-up visits every 3 to 6 months

Extension

Participants with disease progression on everolimus may cross-over to receive lutetium Lu 177 dotatate.

What Are the Treatments Tested in This Trial?

Interventions

• Everolimus
• Lutetium Lu 177 Dotatate

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm I (lutetium Lu 177 dotatate) Experimental Treatment 8 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 Control 8 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.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Lutetium Lu 177 dotatate (Lutathera®) is an approved targeted therapy specifically for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), offering a new treatment option for this heterogeneous group of tumors.

Patients who are already receiving octreotide long-acting release may be eligible for this second-line therapy, highlighting the importance of personalized treatment plans in managing advanced NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. Boucher, JE., Sommers, R.[2019]

The study successfully demonstrated that pharmacokinetic parameters of Lu-177 DOTATATE can be derived from SPECT/CT imaging, allowing for non-invasive monitoring of drug distribution in patients with neuroendocrine tumors.

The findings revealed significant differences in drug clearance and distribution between blood and bone marrow, suggesting that individual patient characteristics, such as weight, can be used to optimize personalized dosing strategies for improved treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of Radiopharmaceuticals from SPECT/CT Image Acquisition by Contouring in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Lu-177 DOTATATE (Lutathera®) Case. Barakat, A., Santoro, L., Vivien, M., et al.[2023]

In a study of 19 patients with well-differentiated high-grade neuroendocrine tumors treated with Lutetium-177 (177Lu)-DOTATATE, there was a meaningful disease control rate of 72%, with 28% achieving a partial response and 44% having stable disease.

The treatment was generally well-tolerated, with the most common side effects being bone marrow-related, such as thrombocytopenia and anemia, indicating that while effective, monitoring for these toxicities is important in this heavily pre-treated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Response and Clinical Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors to Lutetium-177-DOTATATE. Raj, N., Coffman, K., Le, T., et al.[2023]

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

The LUTIA study is a multicenter randomized controlled trial involving 26 patients with unresectable grade I or II neuroendocrine tumors, aiming to compare intra-arterial (IA) administration of 177Lu-DOTATATE to conventional intravenous (IV) administration to enhance tumor-absorbed doses in liver metastases.

The primary goal is to determine if IA treatment leads to a higher tumor-to-non-tumor uptake ratio of 177Lu-DOTATATE in liver metastases, which could potentially improve treatment response and survival rates for patients with bulky liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-arterial versus standard intravenous administration of lutetium-177-DOTA-octreotate in patients with NET liver metastases: study protocol for a multicenter, randomized controlled trial (LUTIA trial). Ebbers, SC., Braat, AJAT., Moelker, A., et al.[2020]

Citations

1. onclive.com onclive.com/view/lutetium-lu-177-dotatate-yields-partial-responses-in-metastatic-bronchopulmonary-neuroendocrine-tumors

Lutetium Lu 177 Dotatate Yields Partial Responses in ... Lutetium Lu 177 dotatate demonstrated antitumor activity in metastatic BP-NETs, with partial responses in 17% of patients and stable disease in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11137281/

Long-term clinical outcomes of [177Lu]Lu-DOTATATE in ... They established an estimated median PFS of 36.4 months (about 3 years) and the mean OS was 61.9, 52.2, and 38.4 months (about 3 years) in WHO ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04665739

NCT04665739 | Testing Lutetium Lu 177 Dotatate in ... Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors. Detailed Description.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1607427

Phase 3 Trial of 177 Lu-Dotatate for Midgut ... Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/lutathera-neuroendocrine-tumor-initial-treatment

Lutathera Delays Growth of Advanced Neuroendocrine ... Those who received Lu 177-dotatate plus octreotide (Sandostatin) lived almost three times as long without their cancer getting worseExit ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208700s031lbl.pdf

LUTATHERA® (lutetium Lu 177 dotatate) injection, for ... The safety data of LUTATHERA with octreotide was evaluated in NETTER-1 [see ... Patients with progressive, somatostatin receptor-positive midgut carcinoid tumors ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8805789/

Efficacy and Safety of 177Lu-DOTATATE in Lung ... Conclusion: In patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE is effective and safe with a high ...

8. aetna.com aetna.com/cpb/medical/data/900_999/0929.html

Lutetium Lu 177 Dotatate (Lutathera) and ... The recommended dosage is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression, or unacceptable toxicity.