Clinical Research Directory

Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors

This phase III trial studies cabozantinib to see how well it works compared with placebo in treating patients with neuroendocrine or carcinoid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib is a chemotherapy drug known as a tyrosine kinase inhibitor, and it targets specific tyrosine kinase receptors, that when blocked, may slow tumor growth.

Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor

This randomized phase III trial studies octreotide acetate and recombinant interferon alfa-2b to see how well it works compared to octreotide acetate and bevacizumab in treating patients with high-risk neuroendocrine tumors that have spread to other places in the body (metastatic) or spread from where it started to nearby tissue or lymph nodes (locally advanced). Octreotide acetate and recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving octreotide acetate together with recombinant interferon alfa-2b is more effective than giving octreotide acetate together with bevacizumab in treating patients with neuroendocrine tumor.

Testing the Addition of An Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Pancreatic Neuroendocrine Tumors

This phase Ib trial is to find out the best dose, possible benefits and/or side effects of peposertib when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell formation, so as to help block the formation of growths that may become cancer. Radioactive drugs, such as lutetium Lu 177 dotatate, may deliver radiation directly to tumor cells and not harm normal cells. Adding peposertib to lutetium Lu 177 dotatate may kill more tumor cells.

Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable Carcinoid Tumors

This phase II trial studies how well lenvatinib and everolimus work in treating patients with carcinoid tumors that have spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). Lenvatinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

A Study to Investigate Safety and Effectiveness of CRN09682 in Participants With SST2-Expressing NENs and Other Solid Tumors

This Phase 1/2, multicenter, open-label, FIH study aims to evaluate the safety, tolerability, PK, and preliminary antitumor activity of CRN09682 in participants with SST2-expressing NENs and other solid tumors. The study includes a Dose Escalation Phase to determine the MTD and DLTs. Following MTD identification, additional participants will be enrolled at the expansion dose to further assess safety, tolerability, PK, and antitumor activity.

Project: Every Child for Younger Patients With Cancer

This study gathers health information for the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.

Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers

This exploratory study investigates how an imaging technique called 68Ga-FAPi-46 PET/CT can determine where and to which degree the FAPI tracer (68Ga-FAPi-46) accumulates in normal and cancer tissues in patients with cancer. Because some cancers take up 68Ga-FAPi-46 it can be seen with PET. FAP stands for Fibroblast Activation Protein. FAP is produced by cells that surround tumors (cancer associated fibroblasts). The function of FAP is not well understood but imaging studies have shown that FAP can be detected with FAPI PET/CT. Imaging FAP with FAPI PET/CT may in the future provide additional information about various cancers.

Pembrolizumab With Liver-Directed or Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors and Liver Metastases

This pilot phase II trial studies how effective pembrolizumab and liver-directed therapy or peptide receptor radionuclide therapy are at treating patients with well-differentiated neuroendocrine tumors and symptomatic and/or progressive tumors that have spread to the liver (liver metastases). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Liver-directed therapies such as radiofrequency ablation, transarterial embolization, yttrium-90 microsphere radioembolization, and cryoablation may help activate the immune system in order to shrink tumors that are not being directly targeted. Peptide receptor radionuclide therapy is a form of targeted treatment that is performed by the use of a small molecule, which carries a radioactive component attached to a peptide. Once injected into the body, this small molecule binds to some specific sites on tumor cells called receptors and emit medium energy radiation that can destroy cells. Because this radionuclide is attached to the peptide, which binds receptors on tumor lesions, the radiation can preferably be targeted to the tumor cells in order to destroy them. Giving pembrolizumab in combination with liver-directed therapy or peptide receptor radionuclide therapy may work better than pembrolizumab alone.

Determining the Biodistribution of an Imaging Tracer (68Ga-FAPi-46) in Patients With Solid Tumors or Hematologic Cancers

This phase I trial is evaluating a new imaging tracer (68Ga-FAPi-46) with positron emission tomography (PET)/computed tomography (CT) to determine where and to which degree the tracer (68Ga-FAPi-46) accumulates in normal and cancer tissues (the biodistribution) in patients with solid tumors or hematologic (blood) cancers. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case of this research, 68Ga-FAPi-46. Because some cancers take up 68Ga-FAPi-46, it can be seen with PET. CT utilizes x-rays that traverse the body from the outside. CT images provide an exact outline of organs and potential inflammatory tissue where it occurs in a patient's body. Combining a PET scan with a CT scan can help make the image easier to interpret. PET/CT scans are hybrid scanners that combine both modalities into a single scan during the same examination.

A Phase I Study to Assess the Safety and Efficacy of [225Ac]Ac-DOTATATE in Patients With SSTR+ GEP-Nens

This is a phase I study to assess the safety and efficacy of \[225Ac\]Ac-DOTATATE in patients with inoperable, locally advanced or metastatic, progressive, Well-Differentiatedwell differentiated, somatostatin receptor positive gastroenteropancreatic neuroendocrine neoplasms with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT).

Rediscovering Biomarkers for the Diagnosis and Early Treatment Response in NEN (REBORN)

This is a multicentre, controlled, observational prospective study on new biomarkers, as immune profiling, angiogenetic markers and circRNA from TEPs in the diagnosis and in the evaluation of treatment response in pulmonary and gastro-entero-pancreatic NENs.

Sintilimab Combined With IBI310 and Surufatinib for the Treatment of G3-NET and NEC (NESSIE)

This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Sintilimab combined with IBI310 and Surufatinib for the treatment of high-grade advanced-neuroendocrine neoplasm

Absorbed Tumor Dose in Peptide Receptor Radionuclide Therapy with Long-acting Somatostatin Analogues - ATSA Trial

According to current guidelines, patients have to withhalt long-acting somatostatin analogues (LA-SSA) for 4-6 weeks prior to every 177Lutetium-DOTATATE administration. The primary objective of the study is to investigate the effect of LA-SSA on the absorbed dose in tumor lesions during PRRT.

EpigenOMic Determinants of the Neuroendocrine Phenotype As Biomarkers for Neuroendocrine Neoplasms

For GEP mixed neuroendocrine (NE) non-neuroendocrine neoplasms (MiNENs) a key issue affecting prognosis is sometimes the difficulty in obtaining a timely diagnosis, as the NE component is often localized in deeper anatomical locations and/or becomes prevalent over time. The tissue material of biopsies may be not enough to define the NE component when this is particularly small and this could impact on therapeutic decision. Furthermore GEP NENs need to be characterized for potentially druggable biomarkers and liquid biopsy has clear advantage to the solid one to this aim. Here, we will exploit epigenetic differences characterizing NE tumors to build a DNA methylation-based liquid biopsy assay able to detect circulating tumor DNA of NE derivation, to enable the non-invasive diagnosis and monitoring of GEP-MiNENs.

A Study of PM8002 in Combination With Chemotherapy in Patients With NEN

PM8002 is a bispecific antibody targeting PD-L1 and VEGF. This study will evaluate the efficacy and safety of PM8002 in combination with FOLFIRI as second line treatment for neuroendocrine neoplasm (NEC and Ki-67≥55% G3 NET).

Dosimetry Based PRRT Versus Standard Dose PRRT With Lu-177-DOTATOC in NEN Patients

In this study, we want to randomize patients with neuroendocrine neoplasms (NENs) who are eligible for peptide receptor radionuclide therapy (PRRT), to either standard PRRT consisting of 4 treatments with 7.4 GBq Lu-177-DOTATOC (standard arm) or 4 treatments with individualized doses of Lu-177-DOTATOC (dosimetry arm). In the dosimetry arm, the first dose depends on the patients' kidney function and thereafter the absorbed dose to the kidneys at the previous treatment. A max of 20GBq will be administered at the first treatment and 25GBq at treatment 2-4. We aim to reach an accumulated kidney dose of 24Gy. After the first treatment all patients will go through three SPECT/CT scans 24 hours, 4 days, and 7 days, after treatment to calculate absorbed kidney dose. The patients in the standard dose treatment arm will have one SPECT/CT scan after each of the last three treatments; all performed 24 hours after treatment, used to approximate the kidney dose assuming the clearance of the Lu-177 DOTATOC is the same after all treatments. The patients in the dosimetry based treatment arm will go through three SPECT/CT scans after all four treatments for dosimetry calculation. Bone marrow dosimetry is calculated after all treatments in the dosimetry based treatment arm and after the first treatment in the standard treatment arm. For bone marrow dosimetry, blood samples are drawn right before administration of Lu-177 DOTATOC (time 0) and 3 minutes, 45 minutes, 2 hours, 4 hours, 7-8 hours, 24 hours, 4 days, and 7 days after administration of Lu-177 DOTATOC. Standard blood samples are routinely drawn every 2nd week after every treatment in all included patients and analysed regarding liver, kidney and bone marrow function. Kidney clearance is evaluated with Tc-DTPA clearance at baseline. Blood and urinary samples will be collected at baseline and 3 months after the last treatment for kidney fibrosis analyses. At baseline, blood and urine samples are collected for a biobank. All included patients fill in validated quality of life questionaires at all treatments. To evaluate the effect of the treatment, all patients will be evaluated with standard CT scans prior to treatment and 3 and 9 months after the 4th treatment. Ga-68 DOTATOC PET will be performed at baseline and 6 and 12 months after the last treatment.

Protein Molecular Characteristics and Prognosis of Cervical Neuroendocrine Tumors

The clinical diagnosis and treatment data of 300 cases of cervical neuroendocrine tumors were collected, including age, preoperative biopsy pathology results, postoperative histopathological results, TCT results, and colposcopy biopsy pathology results. At the same time, paraffin tissue specimens (remaining specimens after pathological diagnosis) from 100 cases of cervical neuroendocrine tumors from multiple centers across the country were collected to establish a cervical neuroendocrine tumor data follow-up database. Protein concentration and omics analysis were performed on the data results, to evaluate the molecular characteristics and prognosis of cervical neuroendocrine tumor proteins, and to preliminarily explore its clinical application value.

Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients

Neuroendocrine neoplasms (NENs) are a heterogeneous group of lesions derived from cells with the ability to produce hormones that may arise from multiple different organs. Their clinical behavior is quite variable, encompassing both benign lesions and aggressive tumors that invade surrounding and/or distant structures. NENs may also cause serious morbidity due to hormone oversecretion. NENs are among the most frequently inherited human tumors, presenting either isolated or as part of syndromes in which a single patient or family develops multiple tumors. There are also non-inherited changes in the genetic information of the tumor cells that are potential targets for treatment. Both inherited and non-inherited DNA defects can be identified using modern routine genetic tests which, unfortunately, are not widely available in Mexico. This project seeks to uncover the genetic defects causing NENs in a large cohort of Mexican patients, using three different methods for genetic testing. Adult individuals with various types of NENs from two reference hospitals in Mexico City will be invited to participate. After completing informed consent, blood and, if possible, tissue samples will be obtained from all participants. Clinical details, laboratory results, imaging studies, and histopathological data at disease presentation will be retrieved. An initial screening will be performed by analyzing changes in the sequence of multiple genes that have been associated with the occurrence of NENs. In cases with negative screening, a specific method to assess changes in the number of copies of the same genes will also be employed. Finally, sequences of all DNA regions encoding information required to make proteins will be obtained in selected cases. Analyses will be carried out in blood and, if available, also in tumor tissue samples from study participants. Screening of additional family members will be offered. This project will accurately describe the repertoire of specific defects causing NENs in the study population, and will likely uncover and characterize novel genetic associations. The results will contribute for a better understanding of the alterations within and outside known driver genes that shape syndromic presentations, tumor behaviors, and inheritance patterns in individuals with NENs. These data will contribute to improve the information on the molecular bases of NENs, including alterations that can be used as therapeutic targets.

Definition of a Multiparametric Prognostic and Predictive System of Classification of NET G3 Patients

The 2017 World Health Organization (WHO) introduced a new category of high-grade, well-differentiated neuroendocrine neoplasms (NENs) that called neuroendocrine tumors (NETs) G3 in pancreatic NENs classification and, then, in 2019, for all gastro-entero-pancreatic (GEP) tract NENs. The new classification made it possible to separate NETs G3 from high-grade, poorly-differentiated, NENs that are called neuroendocrine carcinomas (NECs). However, in clinical practice, we observed that several clinical, pathological and radiological differences are arising among NET G3 patients, suggesting that a multiparametric definition of NET G3 is needed.

YOUNg Adults With Gastro-inteSTinal (GI) and nEuroendocrine canceRs.

The objective of the study is to create a common and unique platform for the acquisition of biological samples and, subsequently, the possible identification of predictive and prognostic biomarkers for young adults with gastrointestinal and neuroendocrine cancers.The definition "adolescent and young adults (AYA)" covers a broad group of patients ranging from the upper limit of the paediatric competence to the youngest patients usually considered and treated as adults. However, a well-defined and universally accepted age range is still not established. Young adults with cancer have distinct epidemiological, biological, and clinical characteristics, as well as special medical and psychosocial needs that are often unmet. In consideration of their poor representation in clinical studies, as well as the rarer, albeit increasing, frequency at an epidemiological level, knowledge of the risk factors associated with cancers in young adults is very poor. It is therefore of fundamental importance to focus attention on this specific cohort of patients, in order to describe in ever more detail any specific biomolecular aspects, and make full use of the pharmacological resources currently available.