Targeted Radiation Therapy Post-Surgery for Metastatic Neuroendocrine Tumors

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt-Ingram Cancer Center

Disqualifiers: Inoperable tumor, Grade 3 neoplasm, Brain metastases, Unstable angina, 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: 9

Duration: 8 months

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase IV trial evaluates how well giving standard of care (SOC) peptide receptor radionuclide therapy (PRRT) after SOC surgical removal of as much tumor as possible (debulking surgery) works in treating patients with grade 1 or 2, somatostatin receptor (SSTR) positive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have spread from where they first started (primary site) to the liver (hepatic metastasis). Lutetium Lu 177 dotatate is a radioactive drug that uses targeted radiation to kill tumor cells. Lutetium Lu 177 dotatate includes a radioactive form (an isotope) of the element called lutetium. This radioactive isotope (Lu-177) is attached to a molecule called dotatate. On the surface of GEP-NET tumor cells, a receptor called a somatostatin receptor binds to dotatate. When this binding occurs, the lutetium Lu 177 dotatate drug then enters somatostatin receptor-positive tumor cells, and radiation emitted by Lu-177 helps kill the cells. Giving lutetium Lu 177 dotatate after surgical debulking may better treat patients with grade 1/2 GEP-NETs

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get personalized advice.

What data supports the effectiveness of the drug Lutetium Lu 177 Dotatate (Lutathera) for treating metastatic neuroendocrine tumors?

Research shows that Lutetium Lu 177 Dotatate (Lutathera) is effective in reducing the size of metastatic neuroendocrine tumors, with some patients experiencing a 20% reduction in tumor size. Additionally, in a study, 22% of patients showed partial response, and 44% had stable disease after treatment with Lutathera. ^{1 2 3 4 5}

Is Lutathera safe for humans?

Lutathera (Lutetium Lu 177 Dotatate) has been generally well tolerated in patients with neuroendocrine tumors, with most side effects being mild. It is approved for use in adults with certain types of neuroendocrine tumors, and studies have shown it to be safe in these cases. ^{3 4 6 7 8}

How is the treatment Lutathera different from other treatments for metastatic neuroendocrine tumors?

Lutathera is unique because it is a type of targeted radiation therapy called peptide receptor radionuclide therapy (PRRT), which specifically targets and binds to somatostatin receptors on tumor cells, delivering radiation directly to the cancer. This approach is different from traditional chemotherapy, which affects all rapidly dividing cells, and is particularly useful for patients with somatostatin-receptor-positive tumors. ^{2 3 4 5 9}

Research Team

Kamran Idrees, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

This trial is for adults with grade 1 or 2 well-differentiated gastroenteropancreatic neuroendocrine tumors that have spread to the liver. Participants must not be pregnant, breastfeeding, and should agree to use contraception. They need a certain level of blood cell counts, kidney function, and no inoperable tumors larger than 3 cm. Those with fully resectable disease or unstable heart conditions are excluded.

Inclusion Criteria

Signed and dated written informed consent

Your white blood cell count must be at least 2000 cells per microliter within the 90 days before your surgery.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

My tumor is a grade 3 neuroendocrine type.

I have previously received PRRT treatment.

I have brain metastases that are either untreated or have grown in the last 90 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgical Debulking

Patients undergo surgical debulking to remove as much tumor as possible

1 day

1 visit (in-person)

Treatment

Patients receive lutetium Lu 177 dotatate intravenously over 30 to 40 minutes on day 1 of each cycle. Treatment repeats every 56 days for up to 4 cycles.

8 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

Treatment Details

Interventions

• Lutetium Lu 177 Dotatate
• Tumor Debulking

Trial Overview The study tests if performing surgery to remove as much tumor as possible before giving a radioactive drug called Lutetium Lu 177 dotatate improves treatment outcomes for patients. The drug targets tumor cells through somatostatin receptors and delivers radiation directly to kill them.

Participant Groups

Group I: Treatment (surgical debulking, 177Lu dotatate) Experimental Treatment 6 Interventions

Patients undergo surgical debulking on day 0 and receive 177Lu dotatate IV over 30 to 40 minutes on day 1 of each cycle. Treatment repeats every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI throughout the trial, and undergo dotatate PET/CT during screening and on study.

Tumor Debulking 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?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

Findings from Research

Peptide receptor radionuclide therapy (PRRT) using 177 Lu-DOTATATE has demonstrated significant efficacy in reducing the size of metastatic neuroendocrine tumors, achieving about a 20% reduction in lesions smaller than 3 cm.

In a specific case involving a 66-year-old man with a rapidly growing 10 cm metastatic nodal conglomerate, PRRT resulted in an impressive size reduction of over 75% after just 2 treatment cycles, indicating its potential effectiveness for aggressive neuroendocrine cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE. Somoza, EA., Duan, H., Shaheen, S., et al.[2022]

Selective internal radiation therapy (SIRT) using (90)Y-labelled resin microspheres demonstrated a 54% objective tumor response rate and a 94% disease control rate shortly after treatment in 40 patients with unresectable liver metastases from neuroendocrine tumors.

The treatment was found to be safe, with mostly mild and manageable adverse effects, although one patient experienced severe complications leading to death, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. Barbier, CE., Garske-Román, U., Sandström, M., et al.[2018]

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]

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]

Neuroendocrine tumors, which make up 1-2% of all cancers, can be slow-growing but may also be aggressive, with a high likelihood of metastasis to the liver, impacting survival rates significantly.

Current treatment options include somatostatin analogues, chemotherapy, and emerging targeted therapies like everolimus and sunitinib, with ongoing clinical trials exploring new strategies to improve outcomes for patients with advanced neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatment of neuroendocrine tumors with hepatic metastases. Demirkan, BH., Eriksson, B.[2019]

The combination of Lutathera and nivolumab was well tolerated in a phase I study involving nine patients with advanced neuroendocrine tumors, with no dose-limiting toxicities observed at the lower dose level.

This treatment showed preliminary signs of antitumor activity, including a partial response in one patient with extensive-stage small cell lung cancer and stable disease in two patients with pulmonary atypical carcinoid, suggesting potential for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung. Kim, C., Liu, SV., Subramaniam, DS., et al.[2021]

In a study of 52 patients with advanced pancreatic neuroendocrine tumors, (177)Lu-DOTATATE therapy demonstrated significant antitumor activity, achieving an overall disease control rate of 81% with both full and reduced dosages.

Patients receiving the higher dosage of 27.8 GBq had a longer progression-free survival compared to those on the reduced dosage of 18.5 GBq, suggesting that the higher dose is more effective and is recommended for eligible patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. Sansovini, M., Severi, S., Ambrosetti, A., et al.[2022]

This study aims to evaluate the efficacy of four additional cycles of Lutathera® compared to two cycles in patients with progressive well-differentiated intestinal neuroendocrine tumors (NET), with a total of 146 patients participating.

The primary goal is to determine if the additional cycles can improve disease control rates over 6 months without increasing safety concerns, potentially leading to new treatment recommendations for extending patient survival and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized, phase II study to assess the schemas of retreatment with Lutathera® in patients with new progression of an intestinal, well-differentiated neuroendocrine tumor (ReLUTH). Deshayes, E., Assenat, E., Meignant, L., et al.[2022]

The review highlights the importance of somatostatin analogs and peptide receptor-targeted therapies in the treatment of neuroendocrine tumors, showcasing their efficacy in managing the disease.

It emphasizes the need for improved clinical trial designs and the development of biomarkers to better assess treatment outcomes and guide future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. Kulke, MH., Scherübl, H.[2021]

References

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

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. [2018]

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

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

4. 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]

5. Turkey pubmed.ncbi.nlm.nih.gov

Systemic treatment of neuroendocrine tumors with hepatic metastases. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A prospective, randomized, phase II study to assess the schemas of retreatment with Lutathera® in patients with new progression of an intestinal, well-differentiated neuroendocrine tumor (ReLUTH). [2022]

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

Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. [2021]