Targeted Radiation Therapy Post-Surgery for Metastatic Neuroendocrine Tumors
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Vanderbilt-Ingram Cancer Center
Disqualifiers: Inoperable tumor, Grade 3 neoplasm, Brain metastases, Unstable angina, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
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.
12345Is 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.
34678How 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.
23459Eligibility 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.
+12 more
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.
+4 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (surgical debulking, 177Lu dotatate)Experimental Treatment6 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Vanderbilt University/Ingram Cancer CenterNashville, TN
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Who Is Running the Clinical Trial?
Vanderbilt-Ingram Cancer CenterLead Sponsor
References
Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE. [2022]Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions
Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. [2018]To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs).
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. [2022]Label="BACKGROUND">Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors.
Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting. [2023]Neuroendocrine tumors (NETs) are rare, but the incidence and prevalence of NETs are increasing in the United States. While surgery is the preferred treatment for NETs, it is not a viable option for metastatic disease. Lutathera (177Lu-DOTATATE) is approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of gastroenteropancreatic (GEP)-NETs in adults. There is limited information on GEP-NET treatment responses to Lutathera.Our institution launched a peptide receptor radionuclide therapy (PRRT) service line using Lutathera with involvement from a multidisciplinary team and complete collaboration between hospital administration and clinical providers. A prospective registry study was also established in order to collect patient demographics and clinical data regarding the treatment of GEP primary NETs with Lutathera.Between August 2018 and July 2020, 35 GEP-NET patients were treated with Lutathera, of which 65.71% received 4 complete cycles and 25.71% received 3 cycles; 5.71% and 2.86% received 2 and 1 cycles of PRRT, respectively. Most adverse events during the course of our study were low grade using the common terminology criteria for adverse events system. Of the patients who completed all 4 cycles: 22% showed partial response to Lutathera, 44% showed stable disease, and 13% showed disease progression based on a qualitative assessment of positron emission tomography/computed tomography imaging.From our experience, Lutathera was well tolerated in patients with GEP-NET. Additional studies are needed to examine long-term clinical and patient-reported outcomes associated with GEP-NET treatment as well as financial considerations for hospitals embarking on a PRRT program.
Systemic treatment of neuroendocrine tumors with hepatic metastases. [2019]Neuroendocrine tumors, 1-2% of all malignancies, are relatively slow-growing neoplasms. The majority of neuroendocrine tumors belong to the World Health Organization Group 2 with well-differentiated endocrine carcinomas, but some tumors can be aggressive. The most common are gastroenteropancreatic-neuroendocrine tumors, followed by bronchopulmonary neuroendocrine tumors; less frequent locations are the ovaries, testis and hepatobiliary locations. They can be either non-functioning tumors with symptoms related to mass effects and malignant tumor disease or functioning tumors with specific hormones/neuropeptides autonomously secreted to induce specific clinical syndromes. Localized neuroendocrine tumors are less frequent than metastatic ones; in fact, up to 75% of patients with small bowel neuroendocrine tumors and 30-85% of pancreatic neuroendocrine tumors present with liver metastases either at the time of diagnosis or during the course of the disease. The predominant metastatic site is the liver, which is the best prognostic marker of survival regardless of the primary site. If surgical resection or interventional therapies of the hepatic tumor burden are not feasible, or if the metastases are not confined to the liver, systemic treatment remains the only option. None of the systemic therapies is liver-specific, but rather acts on all metastatic sites. The lack of prospective studies comparing different treatment modalities in homogeneous cohorts of patients makes the best treatment strategy poorly defined. Standard systemic therapy options are somatostatin analogues (octreotide and lanreotide), interferon-α and chemotherapy. Somatostatin analogues not only control symptoms related to functioning tumors but tumor growth as well. Because of the studies challenging its efficacy, as well as the potential for side effects, the more widespread acceptance of interferon-α in the treatment of metastatic neuroendocrine tumors has been limited. Well-differentiated neuroendocrine tumors do not show high sensitivity to chemotherapy because of their low mitotic rates, high levels of antiapoptotic protein bcl-2 and increased expression of the multi-drug resistant gene. Traditional chemotherapeutic agents are streptozotocin in combination with 5-fluorouracil or doxorubicin, or to some extent dacarbazine. Temozolomide, capecitabine and oxaliplatin, as monoagents or in combination therapy, show efficacy in phase II trials. Patients with poorly differentiated neuroendocrine tumor, regardless of the primary tumor localization, are candidates for cisplatin and etoposide chemotherapy regimen. Peptide receptor radionuclide therapy is reported to be an effective treatment option for patients with good performance status and high somatostatin-receptor scintigraphy uptake as well as without major liver involvement. Basic fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, transforming growth factor alpha and beta, insulin-like growth factor type 1, epidermal growth factor, stem cell factor (c-kit), and corresponding receptors have been shown to be expressed in Neuroendocrine tumors. Current phase II-III clinical trials with molecular-targeted therapies revealed promising agents such as everolimus (RAD001), an oral mTOR inhibitor, and sunitinib malate (SU-11248), an oral multitargeted tyrosine kinase inhibitor against vascular endothelial growth factor receptors, platelet-derived growth factor receptors, c-kit receptors, glial cell linederived neurotrophic factor, and FMS-like tyrosine kinase-3 (Flt 3), which were approved for the treatment of advanced pancreatic neuroendocrine tumors. Ongoing clinical trials with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, will further define the role of angiogenesis inhibitors in advanced intestinal neuroendocrine tumors. Various further novel strategies of targeted therapy and microRNA-regulated pathways in neuroendocrine tumors are under development.
Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung. [2021]Label="BACKGROUND">Lutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.
Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. [2022]We evaluated the activity and safety profile of (177)Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced G1-G2 pancreatic neuroendocrine tumors.
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]Label="BACKGROUND" NlmCategory="BACKGROUND">Although neuroendocrine tumors (NET) are classed as rare, they have a high prevalence and their incidence is increasing. Effective treatment with lutetium 17-[177Lu]Lu-oxodotreotide (Lutathera®) is possible in patients with well-differentiated NET, improving progression-free survival (PFS), overall survival (OS), and quality of life (QoL). However, progression does occur. Retreatment with additional Lutathera® cycles is an option to extend PFS and OS. Two retreatment cycles are usually proposed. We aim to compare four versus two Lutathera® retreatment cycles in patients with new progression of a well-differentiated intestinal NET.
Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. [2021]Overview of the Disease ProcessIncidencePrognostic FactorsGeneral Therapy StandardsAccomplishments and Lack of Accomplishments During the YearSomatostatin AnalogsPeptide Receptor-Targeted TherapySelective Internal Radiotherapy (SIRT)CYTOTOXIC THERAPIES: TemozolomideVEGF Pathway InhibitorsmTOR InhibitorsDevelopment of BiomarkersWhat Needs to be Done (Application of the Accomplishments)Controversies and DisagreementsHistologic Classification and Staging of Neuroendocrine TumorsClinical Trial Design and End PointsFuture Directions.