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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will look at whether it is practical and safe to give Lutathera directly into an artery of the liver (hepatic intraarterial infusion). The researchers will compare the effects of hepatic intraarterial infusion in the liver with the effects of the standard approach (intravenous infusion in the arm). The researchers will also determine whether Lutathera is effective against participants' cancer.

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 data supports the effectiveness of the treatment Lutathera for neuroendocrine tumors?

Lutathera (177Lu-DOTATATE) has been shown to be effective in treating neuroendocrine tumors, with studies indicating that it can lead to partial responses or stabilize the disease in many patients. For example, in a study of patients with gastroenteropancreatic neuroendocrine tumors, 22% showed partial response and 44% had stable disease after treatment. ^{1 2 3 4 5}

Is Lutathera (177Lu-DOTATATE) safe for treating neuroendocrine tumors?

Lutathera (177Lu-DOTATATE) is generally well tolerated in patients with neuroendocrine tumors, but it can have side effects like potential damage to the kidneys, liver, and blood cells, and there is a risk of developing another type of cancer. Most side effects reported in studies were mild, but more research is needed to understand long-term safety. ^{2 4 5 6 7}

What makes the drug Lutathera unique for treating neuroendocrine tumors?

Lutathera (177Lu-DOTATATE) is unique because it is a targeted therapy that uses a radioactive substance to specifically bind to and attack neuroendocrine tumor cells with somatostatin receptors. It is administered intravenously and allows for imaging to monitor how the drug is distributed in the body, which helps in optimizing individual dosages. ^{1 4 8 9 10}

Research Team

Lisa Bodei

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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&#174;) Case. Barakat, A., Santoro, L., Vivien, M., 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]

References

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

Homologous Recombination Repair Defect May Predict Treatment Response to Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors. [2022]

2. United States 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. [2023]

3. Japan 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. [2022]

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

Safety and Efficacy of 177 Lu-DOTATATE in Neuroendocrine Tumor Patients With Extensive Bone Disease. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life. [2021]

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

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. [2022]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

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

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

9. 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&#174;) Case. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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