Lutetium Lu 177 Dotatate for Lung Carcinoid Tumor

Recruiting in Palo Alto (17 mi)

+28 other locations

Overseen by Thomas A Hope

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment Lutetium Lu 177 Dotatate for lung carcinoid tumors?

Lutetium Lu 177 Dotatate has been shown to increase survival and response rates in patients with neuroendocrine tumors, which are similar to lung carcinoid tumors, by targeting specific receptors on the tumor cells. ^{1 2 3 4 5}

How is the drug Lutetium Lu 177 Dotatate unique for treating lung carcinoid tumors?

Lutetium Lu 177 Dotatate is unique because it is a targeted therapy that uses a radioactive substance to specifically bind to somatostatin receptors on neuroendocrine tumors, including those in the lung, delivering radiation directly to the cancer cells while minimizing damage to surrounding healthy tissue. This approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{1 2 3 4 6}

Research Team

Thomas A Hope

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

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.

Trial Timeline

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.

Treatment Details

Interventions

• Everolimus (mTOR Inhibitor)
• Lutetium Lu 177 Dotatate (Radioactive Drug)

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.

Participant Groups

Group I: Arm I (lutetium Lu 177 dotatate) Experimental Treatment 7 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 7 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat Gastroenteropancreatic Neuroendocrine Tumors. [2019]

3. England 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). [2020]

4. France 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment Response and Clinical Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors to Lutetium-177-DOTATATE. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Radiation Safety Observations Associated with 177Lu Dotatate Patients. [2020]