PRRT for Neuroendocrine Tumors

Recruiting in Palo Alto (17 mi)

Overseen by Brendan C Visser, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Stanford University

Must be taking: Octreotide LAR

Must not be taking: Chemotherapy, Everolimus, Sunitinib

Disqualifiers: Brain metastases, Bone metastases, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for patients with specific types of neuroendocrine tumors. The treatment aims to improve survival by targeting and killing cancer cells using radiation.

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.

What data supports the effectiveness of the treatment Lutathera (Lutetium Lu 177 dotatate) for neuroendocrine tumors?

Lutathera (Lutetium Lu 177 dotatate) has been shown to be effective for treating certain neuroendocrine tumors, as it was approved by the FDA based on positive results from the NETTER-1 trial. This treatment works well for tumors that have specific receptors (somatostatin receptors) and has shown promising results in patients with advanced neuroendocrine tumors. ^{1 2 3 4 5}

Is Lutetium Lu 177 dotatate (PRRT) safe for humans?

Lutetium Lu 177 dotatate (PRRT) is generally considered safe, 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. It has been approved by the FDA for treating certain neuroendocrine tumors, and studies have shown it to be effective, though some concerns exist for patients with specific medical histories. ^{1 6 7 8 9}

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

Lutathera is unique because it is a targeted therapy that uses a radioactive substance to bind to somatostatin receptors on neuroendocrine tumors, delivering radiation directly to the cancer cells. This approach is particularly useful for tumors that are inoperable and have not responded to standard treatments. ^{3 4 5 8 10}

Research Team

Brendan C Visser, MD

Principal Investigator

Stanford Universiy

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Lutathera (Radiopharmaceutical)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

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

Findings from Research

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]

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]

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 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]

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 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 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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Peptide Receptor Radionuclide Therapy With 177Lu-Octreotate in Patients With Somatostatin Receptor Expressing Neuroendocrine Tumors: Six Years' Assessment. [2020]

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

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. [2023]

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

ACR-ACNM-ASTRO-SNMMI Practice Parameter for Lutetium-177 (Lu-177) DOTATATE Therapy. [2023]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival. [2018]

8. United States 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. [2022]

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

Real world outcomes in patients with neuroendocrine tumor receiving peptide receptor radionucleotide therapy. [2023]

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

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