Lutathera for Neuroendocrine Tumors

Overseen By Lisa Bodei, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Radiolabeled somatostatin analogs

Disqualifiers: Pregnancy, Liver involvement, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of delivering the treatment Lutathera (177Lu-DOTATATE) directly into the liver to determine if it is more effective and safer than the standard intravenous method. Lutathera treats certain types of neuroendocrine tumors, which often originate in the digestive system or lungs. Suitable candidates for this trial have progressive, non-operable neuroendocrine tumors primarily affecting the liver and displaying specific markers on imaging tests. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, previous oral chemotherapy or biotherapy must be completed more than 4 weeks before joining the study, and there are specific requirements for Octreotide use.

What prior data suggests that hepatic intraarterial infusion of Lutathera is safe?

Research has shown that 177Lu-DOTATATE was well-tolerated in past studies. Patients who received this treatment lived longer without their cancer worsening and had an overall longer survival time. The treatment proved generally safe for patients with neuroendocrine tumors.

Some side effects occurred but were usually manageable. Common side effects included nausea, vomiting, and mild tiredness, while serious side effects were rare. The FDA has already approved this treatment for certain types of neuroendocrine tumors, indicating a good safety record based on existing data.

This trial is testing a new delivery method, directly into the liver. While this method is new, the treatment itself has demonstrated a strong safety record in other studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for neuroendocrine tumors, which typically involve surgery, chemotherapy, or targeted therapies, 177Lu-DOTATATE offers a novel approach by using targeted radiotherapy. This treatment is unique because it involves a radioactive compound, lutetium-177, which directly delivers radiation to tumor cells, minimizing damage to surrounding healthy tissues. Additionally, 177Lu-DOTATATE is administered both intra-arterially and intravenously, allowing for a potentially more effective delivery of the therapy. Researchers are excited about this treatment due to its targeted mechanism of action, which could lead to improved outcomes and fewer side effects compared to conventional therapies.

What evidence suggests that Lutathera might be an effective treatment for neuroendocrine tumors?

Research has shown that 177Lu-DOTATATE, the treatment under study in this trial, effectively treats neuroendocrine tumors. Studies have found that it can help patients live longer without cancer progression. Specifically, patients receiving this treatment responded significantly better than those on traditional therapies. Additionally, those who took 177Lu-DOTATATE with octreotide lived almost three times longer without cancer progression. Overall, this treatment appears promising for improving both survival and quality of life in patients with neuroendocrine tumors. ^{4 6 7 8 9}

Who Is on the Research Team?

Lisa Bodei

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of neuroendocrine tumors that have spread to the liver and are not suitable for surgery. Participants must have a positive somatostatin-receptor, measurable disease progression, and be in relatively good health with an ECOG performance status of 0 or 1. They should agree to use contraception and can't join if they've had certain prior treatments like radiolabeled somatostatin analogs or extensive chemotherapy.

Inclusion Criteria

I cannot undergo surgery to cure my condition, but past surgeries are okay if they were over 6 weeks ago.

A disease that can be measured using the RECIST 1.1 guidelines, with at least one dimension measuring 1.0 cm or more.

Any new skin lesion that appears should be evaluated by a healthcare professional.

Exclusion Criteria

My kidney function is poor, with high creatinine or low filtration rate.

I have severe urinary incontinence that makes certain cancer treatments unsafe.

My liver is mostly affected by cancer, as confirmed by a radiologist.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four administrations of 177Lu-DOTATATE, two intra-arterial followed by two intravenous, two months apart with renal protective amino acid solution co-administration

4-6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-DOTATATE

Trial Overview The study tests Lutathera (177Lu-DOTATATE) delivered directly into the liver's artery versus standard intravenous infusion. It aims to determine which method is safer, more practical, and effective against cancer by comparing their effects on tumor growth.

How Is the Trial Designed?

Group I: PRRT with 177Lu-DOTATATE Experimental Treatment 1 Intervention

Patients will undergo a routine 68Ga-DOTATATE PET/CT. Patients with sufficient tumor uptake will be offered therapy with 177Lu-DOTATATE. The treatment regimen will consist of four administrations of 177Lu-DOTATATE-two intra-arterial followed by two intravenous, two months apart (+/- 2 weeks), with renal protective amino acid solution co-administration.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study of 229 patients with advanced midgut neuroendocrine tumors, treatment with lutetium-177 (177Lu)-Dotatate significantly improved progression-free survival (65.2% at 20 months) compared to octreotide LAR alone (10.8%).

The 177Lu-Dotatate group also showed a higher response rate (18% vs. 3%) and preliminary evidence of improved overall survival, with manageable side effects, including low rates of severe myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. Strosberg, J., El-Haddad, G., Wolin, E., et al.[2022]

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&#174;) Case. Barakat, A., Santoro, L., Vivien, M., et al.[2023]

In a study of 71 patients aged 70 and older with advanced neuroendocrine tumors treated with 177Lu-DOTATATE, the treatment showed a median progression-free survival of 36 months and overall survival of 47 months, indicating its efficacy in this age group.

The treatment was well-tolerated, with only 2.8% experiencing significant myelosuppression, and there was no decline in health-related quality of life, suggesting that 177Lu-DOTATATE is a safe option for older patients with advanced NET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life. Chen, L., Navalkissoor, S., Quigley, AM., et al.[2021]

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]

In a study involving 35 patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with Lutathera (177Lu-DOTATATE), the treatment was well tolerated, with most adverse events being low grade.

Among patients who completed all 4 cycles of Lutathera, 22% showed a partial response, 44% had stable disease, and 13% experienced disease progression, indicating Lutathera's potential efficacy in managing GEP-NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting. Mejia, A., Vivian, E., Nwogu, C., et al.[2023]

In a phase 1/2 study involving 15 Japanese patients with advanced neuroendocrine tumors, 177 Lu-DOTATATE treatment resulted in a 53% objective response rate, indicating significant tumor shrinkage.

The treatment was well-tolerated, with absorbed radiation doses to the kidneys and bone marrow remaining within safe limits, although some patients experienced Grade 3 adverse events like lymphopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and response after peptide receptor radionuclide therapy with 177 Lu-DOTATATE for neuroendocrine tumors in phase 1/2 prospective Japanese trial. Kudo, A., Tateishi, U., Yoshimura, R., et al.[2022]

177 Lu-DOTATATE therapy in 30 patients with neuroendocrine tumors and extensive bone metastases showed a median progression-free survival of 27 months and overall survival of 35 months, indicating its efficacy in this challenging patient population.

The treatment was generally safe, with only 10% experiencing severe bone marrow toxicity and no cases of severe kidney toxicity, while patients reported significant improvements in their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease. Alsadik, S., Gnanasegaran, G., Chen, L., 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]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

Lutetium-177-dotatate (177 Lu-dotatate) is an FDA-approved treatment for advanced somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs), based on positive results from the NETTER-1 trial.

A case study presented shows that a patient with a grade 3 pancreatic neuroendocrine tumor and a BRCA1 germline mutation experienced a significant response to 177 Lu-dotatate, suggesting its potential efficacy even in more aggressive tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. Zhu, M., Bassam Sonbol, M., Halfdanarson, T., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK587368/

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI Clinical trials, including the landmark NETTER-1 study, have demonstrated significant improvements in progression-free survival, quality of life ...

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

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

3. lutathera-hcp.com lutathera-hcp.com/1l-netter-2-efficacy

1L: NETTER-2 | LUTATHERA® (lutetium Lu 177 dotatate) | HCP Overall Response Rate (Full Analysis Set) ... 43% overall response rate for LUTATHERA plus 30 mg octreotide, which is 4x greater ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/65/5/746

Effectiveness and Safety of Retreatment with 177Lu ... A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40404399/

Clinical Outcomes of 177 Lu-DOTATATE Peptide Receptor ... This study assessed real-world clinical outcomes of 177Lu-DOTATATE PRRT in this patient subgroup. Methods: Data from consecutive patients with ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/66/3/449

Dosimetry of [177Lu]Lu-DOTATATE in Patients with Advanced ... Dosimetry of [177Lu]Lu-DOTATATE in Patients with Advanced Midgut Neuroendocrine Tumors: Results from a Substudy of the Phase III NETTER-1 Trial.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38514088/

Effectiveness and Safety of Retreatment with 177 Lu- ... A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.LBA588

[177Lu]Lu-DOTA-TATE in newly diagnosed patients with ... Conclusion: 177Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, compared with high-dose octreotide LAR, in ...