View clinical trials related to Neuroendocrine Tumors.
Filter by:This study is Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors
Neuroendocrine neoplams (NENs) are uncommon, but with a significant increasing incidence and prevalence with advances in diagnostic techniques. NENs can originate from various parts of the body and are highly heterogeneous. Neuroendocrine tumors (NET), dividing into G1, G2, G3, are well-differentiated types with slow growth and neuroendocrine carcinoma (NEC) are poorly-differentiated with high malignancy. Pancreatic carcinoma is one of the malignant neoplasms with a very high mortality rate. For NET G3, NEC and pancreatic, there are limited treatment options especially for those who progressed on standard chemotherapy. Surufatinib is a novel multi-targeted kinase inhibitor on VEGFR-1, 2, 3, FGFR1, and CSF1R, which has required the China NMPA approval on unresectable NETs (G1&G2). The pivital phase III clinical trial on NEC is ongoing. Sintilimab is a PD-1 inhibitor with the approval on gastric cancer, non-small cell lung cancer, hepatocellular carcinoma and Hodgkin lymphoma. Clinical evidence has shown the anti-tumor activity of surufatinib in combination with PD-1 inhibitor in solid tumors, including NEN, small-cell lung cancer, G/GEJ cancer, etc. The current study is to investigate the safety and efficacy of surufatinib in combination with sintilimab in the treatment of NET G3, NEC and pancreatic carcinoma, in order to provide more treatment options for the patients who failed standard chemotherapy.
Doctors and researchers leading this study hope to learn more about peptide receptor radionuclide therapy (PRRT) in combination with cytoreduction (surgically removing tumors). They hope to learn if combining PRRT in combination with cytoreduction would be more effective than cytoreduction alone. PRRT itself is approved by the U.S. Food and Drug Administration (FDA) for people with PanNETs however the combination with cytoreduction is considered experimental. Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.
Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, that tend to be slow growing and are often diagnosed when metastatic. Surgery is the sole curative option, but is feasible only in a minority of patients. Peptide Receptor Radionuclide Therapy (PRRT) has been experimented for almost 20 years and is an established effective therapeutic modality for well/moderately differentiated, inoperable or metastasized gastro-entero-pancreatic (GEP) and bronchial NETs. Clinical studies demonstrated that partial and complete objective responses can be obtained in up to 30% of patients. Side effects may involve the kidneys and the bone marrow and are usually mild. Renal protection is used to minimize the risk of a late decrease of renal function. A new application for P-NETs is preoperative PRRT. Since surgery is the only curative option for GEPNETs, preoperative PRRT could increase the efficacy of surgery. However, this modality has not been fully explored in dedicated studies and there are just few sporadic case reports that described the preoperative use of PRRT in pancreatic NETs who could then be operated on successfully. Moreover there are few experiences demonstrating the advantage of PRRT associated to surgery in a multidisciplinary setting. In addition, the possibility of detecting the circulating NET transcripts by means of transcriptome analysis could represent an early marker of response to PRRT and improve the patient management. Aim of this study is to evaluate the response and rate of R0 surgery in patients with unresectable or borderline resectable PNETs eligible to PRRT with 90Y-DOTATOC and correlate the response to the variation in circulating NET transcripts measured before and after the end of PRRT. It has been recently shown that a PCR-based 51 transcript signature is significantly more sensitive and efficient than single analytes (e.g. CgA) in NET diagnosis and follow up. 30 patients will be enrolled in the study; each of them will receive 1.85 GBq/cycle of 90Y-DOTATOC with a cumulative activity of 9.25-11.1 GBq in 5-6 cycles (depending on personalized dosimetry). Therapy response will be assessed by morphological (CT/MRI) and functional (PET/CT or Octreoscan) imaging after 3 and 6 months from the completion of PRRT and compared with transcript analysis. Based on literature reports we expect a response rate of about 35% of patients.
The current study aims to access the feasibility, safety, and efficacy of EUS-FNI for nonfunctional pNETs
Imaging procedures such as 1-(2-[18F]FLUOROETHYL)-L-Tryptophan PET/CT in patients with cancers may help doctors assess a patient's response to treatment and help plan the best treatment in the future. The purpose is to see if there can be a better differentiation of tumor and non-tumor tissue where the tumor tissue has a higher uptake of Tryptophan.
The present study aims to evaluate the feasibility, safety and efficacy of EUS-FNI for MEN1-related pNETs
Study design and rationale: Neuroendocrine neoplasms (NENs ) represent a heterogeneous group of malignancies, which differ in terms of behavio r and prognosis. Most of t hem are advanced at diagnosis t herefore systemic treatment is proposed. While over the last years many advanced have been made especially in terms of molecular targeted therapies (MTA) like everolimus and sunitinib, chemotherapy i n NENs still represents a controversial question. Temozolomide has been reported to be active alone or in combination with other drugs in neuroendocrine neoplasms (NENs) from different origin. So far there is not universal agreement on the right setting an d way of administration of this therapy. Objective: This is a multicentric phase II prospective interventional study to evaluate the clinical features of patients, who are judged unfit for systemic treatments, consecutively treated with a metronomic Temozolomide chemotherapy schedule in Italian centers with expertise in NEN and to explore also the methylation status of O6-methylguanine-DNA-methyltransferase (MGMT) and the polymorphism of thymidylate synthase (TS) by pyrosequencing in those patients of which tissues were available. This study will allow a better understanding of the role of metronomic temozolomide chemotherapy in NENs patients and help clinicians in answering some of the outstanding questions on their management. Method: Prospective analysis of clinical data of patients unfit for chemotherapy consecutively treated with metronomic temozolomide regimen in Italian centers with expertise in clinical and research NEN activity, for one year from the start of the accrual. Planning of study: Data from NENs patients of any age treated at these centers will be retrieved by searching the hospital information system and analysed. Eligible study population: Patients with histological diagnosis of low grade advanced NEN treated unfit for systemic treatments, for one year from the start of the accrual. Endpoints and evaluation parameters: Description of efficacy and toxicity of Temozolomide regimen in patients with advanced NENs with different primary sites unfit for systemic treatment and explored the pote ntial correlation with clinical/biological factors.
The theranostic principle is based on the use of radiolabeled compounds which can be applied for diagnostic molecular imaging and targeted delivery of radiation to the tumor. Gastrointestinal tumors (GIT), including gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) also express a phenotypic biomarker called prostate-specific membrane antigen (PSMA), thereby rendering it a potential diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy. Aim is to evaluate whether PSMA-directed in-vivo imaging can be also applied to GEP-NEN patients to determine if i) biopsy-derived tissue of newly diagnosed patients exhibit a PSMA expression profile, ii) PSMA-PET shows upregulated PSMA expression in-vivo, iii) such a molecular imaging approach identifies more disease sites relative to conventional imaging, and iv) if the PSMA PET signal predicts further clinical course and outcome under guideline-compatible treatment.
Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-[Tyr3]octreotate (177Lu-DOTATATE) is a form of internal radiation treatment for patients with neuroendocrine tumors (NET) to reduce tumor growth and stabilize disease. Due to limited response rates, there is a need to improve this therapy. A better understanding of therapeutic radiobiological responses, such as transcriptional and DNA damage responses, could contribute to identification of biomarkers for toxicity and/or efficacy prediction. Easy access to biological samples for biomarker discovery would be via a so-called liquid biopsy (drawing blood) to collect healthy peripheral blood mononuclear cells (PBMCs) or circulating tumor DNA (ctDNA) for further investigation. Exposure to ionizing radiation (IR) such as by PRRT leads to complex cellular responses including activation of the DNA damage response and changes in gene expression which can differ between individuals. This was previously shown for ex vivo external beam radiation of blood cells in which radiation responsive genes were identified. These genes were also similarly up- or downregulated following in vivo exposure to total-body irradiation of patients. In addition, different studies have shown a good correlation between radiation dose to the blood and DNA double strand break induction in PBMCs for various PRRT-like treatments. These results show that such events can be measured in PBMCs and indicate that ex vivo irradiation can mimic the in vivo transcriptional regulation and DNA damage induction. Therefore, to identify PRRT-induced cellular responses, the investigators will analyze the effects of 177Lu-DOTATATE IR on the transcriptional regulation in PBMCs and compare this regulation to radiation dose and DNA damage induction. In addition, it was shown that levels of ctDNA can be associated with treatment response and anticancer treatment is also shown to influence ctDNA methylation patterns. The investigators will therefore explore dynamics of ctDNA levels and methylation patterns before and after PRRT to provide more knowledge of the effect of radiation response on ctDNA. This is a pilot study to validate the possibility of determining the radiation response of PRRT with 177Lu-DOTATATE in PBMCs and ctDNA.