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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment approach for patients with gastroenteropancreatic neuroendocrine tumors that have spread to the liver. After surgery to remove as much of the tumor as possible (tumor debulking), patients receive a radioactive drug called lutetium Lu 177 dotatate. This drug targets and kills cancer cells by delivering radiation directly to them. People diagnosed with grade 1 or 2 neuroendocrine tumors that show specific receptors (somatostatin receptors) and have spread to the liver might be a good fit. The aim is to determine if this treatment approach better controls the disease. As a Phase 4 trial, this research highlights that the treatment is already FDA-approved and proven effective, focusing on understanding how it benefits more patients.

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 is the safety track record for Lutetium Lu 177 Dotatate and tumor debulking?

Research has shown that Lutetium Lu 177 dotatate is generally safe for people. Studies indicate that common side effects include tiredness, nausea, vomiting, and diarrhea. These side effects occur in more than 15% of patients but are usually manageable. Other research confirms that this treatment does not negatively affect patients' quality of life. Overall, Lutetium Lu 177 dotatate is considered safe for treating certain types of tumors. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for metastatic neuroendocrine tumors focus on surgery, chemotherapy, or somatostatin analogs. But this new approach combines surgical debulking with a radioactive therapy called 177Lu dotatate, which is a type of targeted radiation therapy. Unlike conventional treatments, 177Lu dotatate delivers radiation directly to the tumor cells, potentially minimizing damage to healthy tissues. Researchers are excited about this method because it could offer a more precise attack on cancer cells and might improve outcomes for patients by reducing tumor size more effectively.

What evidence suggests that this trial's treatments could be effective for metastatic neuroendocrine tumors?

Research has shown that Lutetium Lu 177 dotatate, administered to participants in this trial following surgical debulking, effectively treats neuroendocrine tumors (NETs). Studies indicate that this treatment shrinks or stabilizes tumors in nearly half of the patients, achieving a 43% overall response rate. One study found that 17% of patients experienced partial improvement, even when their disease remained stable, highlighting its potential benefits. Additionally, this treatment is well-tolerated and can help control the disease even as it progresses. Overall, Lutetium Lu 177 dotatate has demonstrated promising results in managing NETs, particularly when tumors have metastasized to areas like the liver. ^{1 3 4 6 7}

Who Is on the Research Team?

Kamran Idrees, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11137281/

Long-term clinical outcomes of [177Lu]Lu-DOTATATE in ... The ORR in patients who received [177Lu]Lu-DOTATATE in the 2nd line was 37.5%, 40% in the 3rd line, and 25% in the 4th line. The most frequently ...

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

Clinical Outcomes of 177 Lu-DOTATATE Peptide Receptor ... Conclusion: 177Lu-DOTATATE PRRT is an effective treatment modality for patients with skeletal metastases from NETs (regardless of metastatic ...

3. onclive.com onclive.com/view/lutetium-lu-177-dotatate-yields-partial-responses-in-metastatic-bronchopulmonary-neuroendocrine-tumors

Lutetium Lu 177 Dotatate Yields Partial Responses in ... Lutetium Lu 177 dotatate demonstrated antitumor activity in metastatic BP-NETs, with partial responses in 17% of patients and stable disease in ...

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

Effectiveness and Safety of Retreatment with 177Lu ... Retreatment with 177 Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial ...

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

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

6. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1393317/full

Long-term clinical outcomes of [ 177 Lu]Lu-DOTATATE in ... The most frequently reported (>15%) nonhematologic treatment-related adverse events were fatigue, nausea, vomiting, and diarrhea. Clinically ...

7. mdpi.com mdpi.com/2077-0383/14/7/2384

Evaluation of the Real-Life Efficacy and Safety ... There is strong evidence that therapy with 177LU is safe for the treatment of GEP metastatic tumors and does not affect the quality of life of patients.