PRRT for Neuroendocrine Tumors

Overseen By Brendan C Visser, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must be taking: Octreotide LAR

Must not be taking: Chemotherapy, Everolimus, Sunitinib

Disqualifiers: Brain metastases, Bone metastases, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using Peptide Receptor Radionuclide Therapy (PRRT) both before and after surgery. The main goal is to determine if this treatment, involving a radioactive drug called Lutathera (also known as Lutetium Lu 177 dotatate or 177Lu-DOTATATE), can improve survival rates for patients with tumors that have spread only to lymph nodes or the liver. Ideal participants have these specific tumors, have not recently undergone certain treatments or surgeries, and are on a stable dose of octreotide, a medication for hormone-related tumors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that patients have been on octreotide long-acting release (LAR) at a fixed dose for at least 12 weeks before joining. Other medications like chemotherapy or targeted therapy must be stopped at least 4 weeks before joining.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Lutathera, the treatment under study, is generally safe. One study reviewed over 4,000 cases for side effects, finding that these typically appeared about 114 days after starting treatment, indicating they are not immediate. Another study confirmed that Lutathera is usually well-tolerated during treatment.

Overall, these findings suggest that Lutathera is safe for people with neuroendocrine tumors. However, like any treatment, side effects can occur, so discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lutathera is unique because it uses a targeted approach to treat neuroendocrine tumors. Unlike traditional chemotherapy, which attacks rapidly dividing cells broadly, Lutathera employs a radioactive compound, 177Lu Dotatate, that specifically targets and binds to tumor cells. This allows for precise delivery of radiation directly to the cancer cells, minimizing damage to healthy tissues. Researchers are excited about Lutathera because it not only offers a potentially more effective treatment with fewer side effects but also includes a novel combination of radionuclide therapy followed by surgery for a comprehensive approach to managing the disease.

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

Research has shown that Lutathera, a type of targeted radiation therapy, holds promise in treating neuroendocrine tumors. In the NETTER-1 study, patients who received Lutathera lived an average of 22.8 months without disease progression, compared to 8.5 months with other treatments. Additionally, 43% of patients experienced tumor shrinkage or stabilization. In this trial, participants will receive Lutathera in a structured regimen involving cycles of 177Lu Dotatate, followed by cytoreductive surgery and additional cycles for residual disease. These results suggest that Lutathera could be an effective option for managing neuroendocrine tumors. ^{4 6 7 8 9}

Who Is on the Research Team?

Brendan C Visser, MD

Principal Investigator

Stanford Universiy

Are You a Good Fit for This Trial?

This trial is for adults with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have somatostatin receptors and are WHO Grade 1 or 2. Candidates must be fit for surgery aimed at removing most of the tumor, have not had certain treatments recently, and their major organs must function well.

Inclusion Criteria

I am considered for surgery to remove as much cancer as possible, as decided by a team of cancer specialists.

My scans show my cancer has somatostatin receptors.

You have a specific level of cell growth in your tumor, which will be checked at Stanford.

Exclusion Criteria

My cancer has spread to my bones or abdomen.

I haven't had chemotherapy or targeted therapy in the last 4 weeks.

I have previously received 177Lu Dotatate treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Participants receive 2 cycles of 177Lu Dotatate before surgery

16 weeks

Surgery

Participants undergo cytoreductive surgery

1 week

Post-operative Treatment

Participants may receive additional 177Lu Dotatate (up to 2 cycles) for residual disease

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lutathera

Trial Overview

The study tests Peptide Receptor Radionuclide Therapy (PRRT) using Lutathera before and after surgical removal of tumors in patients with SSTR-positive GEP-NETs. It aims to see if this approach improves survival by combining imaging techniques like PET/CT, CT scans, and MRI.

How Is the Trial Designed?

Group I: Lutathera Experimental Treatment 5 Interventions

2 cycles of 177Lu Dotatate, followed by cytoreductive surgery, followed by additional 177Lu Dotatate (up to 2 cycles) for residual disease as determined by 68Ga DOTA TATE PET/CT

Lutathera is already approved in United States, European Union for the following indications:

Approved in United States as Lutathera for:

• Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults and pediatric patients 12 years and older

Approved in European Union as Lutathera for:

• Treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

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]

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]

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is a safe and effective treatment for patients with inoperable or metastatic neuroendocrine neoplasia (NEN), showing a clinical response of regressive disease in 47.6% of cases.

The study found no severe renal or hematological toxicity in 30 patients treated with Lu-DOTATATE, suggesting that while hematological parameters may influence survival, the treatment itself is well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. Löser, A., Schwarzenböck, SM., Heuschkel, M., et al.[2018]

In a real-world study of 65 patients with somatostatin-receptor-positive neuroendocrine tumors (NETs) treated with 177Lu-Dotatate (Lu-177), 26.9% achieved a partial response, indicating promising efficacy in this patient population.

Patients with non-functional NETs showed significantly better treatment responses, with a 42.3% partial response rate and a 96% disease control rate, suggesting that tumor functionality may influence the effectiveness of Lu-177 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world outcomes in patients with neuroendocrine tumor receiving peptide receptor radionucleotide therapy. Hentzen, S., Mehta, K., Al-Rajabi, RMT., et al.[2023]

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]

Lutetium-177 (Lu-177) DOTATATE is an effective treatment for inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have not responded to standard therapies, as it can reduce tumor size, improve symptoms, and increase progression-free survival.

The practice parameter document ensures safe handling and administration of Lu-177 DOTATATE, providing essential guidelines for authorized users to maintain consistent and safe treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. Love, C., Desai, NB., Abraham, T., et al.[2023]

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 of 143 patients with somatostatin-expressing neuroendocrine tumors, treatment with Lu-DOTATATE showed no significant increase in toxicity for patients with a history of regional chemoembolization and radionuclide hepatic embolization (CRHE).

Patients with a history of CRHE had a statistically significant higher rate of stable disease and lower rates of disease progression after Lu-DOTATATE therapy, indicating that prior CRHE is not a contraindication for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy After Regional Hepatic Embolization in Patients With Somatostatin-Expressing Neuroendocrine Tumors. Hamiditabar, M., Ali, M., Bolek, L., et al.[2022]

In a study of 144 patients with metastatic neuroendocrine tumors, Lu DOTATATE therapy demonstrated a cumulative disease control rate of 59.09%, indicating it can effectively manage tumor progression in this patient population.

The therapy was found to be safe, with no grade 3 or 4 renal toxicities reported, although some patients experienced grade 3 and 4 hematological and hepatotoxic adverse events, which were generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide Receptor Radionuclide Therapy With 177Lu-Octreotate in Patients With Somatostatin Receptor Expressing Neuroendocrine Tumors: Six Years' Assessment. Hamiditabar, M., Ali, M., Roys, J., et al.[2020]

Lutetium-177 (Lu-177) DOTATATE is an effective treatment for inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have not responded to standard therapies, as it can reduce tumor size, improve symptoms, and increase progression-free survival.

The practice parameter document ensures safe handling and administration of Lu-177 DOTATATE, providing essential guidelines for authorized users to maintain consistent and safe treatment practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. Love, C., Desai, NB., Abraham, T., et al.[2023]

Citations

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Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI

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

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1L: NETTER-2 | LUTATHERA® (lutetium Lu 177 dotatate) | HCP

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Results: After data processing, a total of 4284 AE reports associated with Lutathera were analyzed. The median time to AE onset was 113.5 days.

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clinicaltrials.gov/study/NCT04086485

Study Details | NCT04086485 | Lu-177-DOTATATE ...

To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects.