Paraganglioma

This trial studies neuroendocrine tumors, paraganglioma, pheochromocytoma, and other SSTR-positive tumors that are not currently approved for lutetium therapy called LUTATHERA. It aims to evaluate the effectiveness and safety of a similar treatment called lutetium 177Lu edotreotide or 177Lu-DOTATOC in patients who have these diseases but are outside the standard indications for LUTATHERA. The study focuses on expanding knowledge about this therapys role in controlling disease and managing side effects. Participants receive treatment with 177Lu-DOTATOC given by slow intravenous infusion over 30 minutes using a pump system. The dose depends on patient risk factors those with fewer than two risk factors receive 7.4 GBq per cycle, while those with two or more risk factors receive 5.5 GBq per cycle. Each participant will receive 4 cycles of treatment. Risk factors include kidney impairment, previous toxicities, uncontrolled diabetes or hypertension, prior therapies, and disease burden. During the study, participants will have regular assessments over several months, including scans to measure disease control at 32 months and ongoing monitoring up to 44 months for progression-free survival, overall survival, safety, and quality of life. Researchers will check blood tests, organ function, and side effects. This non-randomized phase 2 study allows patients with measurable or evaluable disease and progressive tumors confirmed by imaging to be included, with follow-up to evaluate response and safety.

This research aims to evaluate how well 18F-metafluorobenzylguanidine 18F-MFBG PET imaging detects and measures tumor burden in patients with pheochromocytoma, a type of tumor that highly expresses the norepinephrine transporter NET. The study addresses limitations of current imaging methods, such as low resolution and long procedure times, by assessing a newer tracer that may provide better image quality and faster results. Patients with suspected or confirmed pheochromocytoma will receive a single intravenous injection of 18F-MFBG at a dose of 5.55 MBqkg. After 60 minutes, participants will undergo a PETCT or PETMR scan to visualize the tumors. This imaging method allows for scanning shortly after injection without special preparation, potentially improving diagnostic processes. During the study, researchers will evaluate the safety of 18F-MFBG, the quality of the images, and how accurately the scans correspond to pathological diagnosis and treatment effects. They will monitor false positive and false negative results over about one year. Participants will be assessed through imaging and clinical follow-up, contributing to understanding the tracers diagnostic value in pheochromocytoma.

Researchers are studying the use of 18F-metafluorobenzylguanidine 18F-MFBG positron emission tomography PET to evaluate neuroendocrine tumors, mainly pheochromocytoma, paraganglioma PPGL, and neuroblastoma NB. These tumors express norepinephrine transporter NET, which is targeted by imaging substances like 123I131I-MIBG. However, current imaging methods have limitations such as low resolution and long waiting times, which affect diagnosis. This study aims to assess the safety, image quality, diagnostic accuracy, and tumor burden detection of 18F-MFBG PET in these neural crest tumors.

Researchers are evaluating the use of Gallium-68-DOTATATE PETMRI in patients with somatostatin receptor-positive SSTR-positive central nervous system CNS tumors, mainly focusing on meningioma but also including other tumor types such as esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive systemic cancers metastatic to the brain. The study aims to assess the diagnostic usefulness of this imaging technique, especially in distinguishing tumor recurrence from post-treatment changes, with a particular interest in cases where tumor location limits surgical removal or where patients have higher-grade disease or previous radiation treatment. This is a Phase 4 interventional study sponsored by Weill Medical College of Cornell University.

Researchers are evaluating the safety and efficacy of 225AcAc-DOTATATE in adults with inoperable, locally advanced or metastatic, progressive, well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine neoplasms. This phase I study includes patients who are either new to peptide receptor radionuclide therapy PRRT or have previously received it. The study aims to find a suitable dose and understand the treatments tolerability. Participants receive 225AcAc-DOTATATE infusions every 8 weeks for up to four cycles. The dose escalation phase has two groups one with patients who had prior 177Lu-PRRT treatment and one without. Dose levels range from 90 kBqkg to 120 kBqkg per cycle. Following this, a dose expansion phase groups patients based on their Ki-67 index, a marker of tumor growth. During the study, participants undergo regular assessments including imaging to measure tumor sites, blood tests to monitor organ function and bone marrow capacity, and evaluations of symptoms and side effects. Researchers will measure safety and tolerability up to 32 weeks after the first infusion and determine the recommended dose within 56 days. Additionally, tumor response and disease progression will be tracked for up to 24 months after the last dose. Participants are monitored closely throughout to ensure safety and collect detailed data on treatment effects.

Researchers are investigating CRN09682 in a Phase 12 study to evaluate its safety, tolerability, pharmacokinetics, and early antitumor effects in adults with SST2-expressing neuroendocrine neoplasms NENs and other solid tumors. This first-in-human, multicenter, open-label trial aims to find the maximum tolerated dose MTD and dose-limiting toxicities DLTs through a dose escalation phase. Following this, an expansion phase will further assess safety and effectiveness at the identified dose. Participants will receive CRN09682 intravenously at multiple dose levels every three weeks during the dose escalation phase to determine the MTD and DLTs. Afterward, additional participants will be enrolled in the dose expansion phase at the established dose to continue evaluating safety, tolerability, pharmacokinetics, and antitumor activity. The study includes cohorts with different neuroendocrine tumor types and other SST2-expressing solid tumors. During the study, participants will be monitored for adverse events, dose interruptions, and pharmacokinetic measurements such as drug concentration and exposure levels. Tumor response will be assessed using RECIST 1.1 criteria and somatostatin receptor imaging over approximately two years. Safety follow-up visits will occur up to 30 days after the last dose, with ongoing evaluations for disease progression and overall response throughout the study period.

Researchers are investigating the impact of long-acting somatostatin analogues LA-SSA on the absorbed radiation dose in tumor lesions during peptide receptor radionuclide therapy PRRT for patients with neuroendocrine tumors grade I and II. The study explores whether continuing or stopping LA-SSA treatment before PRRT affects tumor radiation absorption, following current guidelines that recommend withholding LA-SSA 4-6 weeks before PRRT administration. Participants are randomized into three groups one group has not received LA-SSA treatment for at least three months before PRRT, the second group discontinues LA-SSA 4-6 weeks before PRRT, and the third group receives PRRT within one week after their most recent LA-SSA injection. The treatment involves administering 177Lutetium-DOTATATE with scheduled imaging and blood sample collections to assess drug effects and radiation dose. During the trial, participants undergo SPECTCT scans at 4 hours, 24 hours, and between 5 to 7 days after injection to measure absorbed doses in tumors and normal tissues. Blood samples are also collected at multiple timepoints to study pharmacokinetics. Researchers monitor clinical status and performance scores, with the primary outcome focusing on tumor radiation absorption. The study runs until March 2027, with careful follow-up to evaluate treatment impact and safety.

Researchers are studying gene transfer therapy using patients own white blood cells genetically engineered to target specific mutations in metastatic solid tumors. This Phase II trial aims to evaluate if these modified T-cells, alone or with pembrolizumab, can shrink tumors in adults whose cancers have not responded to standard treatments. The study includes participants with various metastatic cancers such as gastrointestinal, genitourinary, breast, ovarian, lung, endocrine tumors, and multiple myeloma with solid masses. Participants receive a preparative regimen of cyclophosphamide and fludarabine to reduce immune cells, followed by infusion of their genetically modified T-cells. Those in one group also receive pembrolizumab before and after the cell infusion. Aldesleukin is administered to support the survival of the infused cells. The treatment process includes leukapheresis to collect white blood cells, cell modification in the lab, hospital stays for infusions and recovery, and extended post-treatment drug regimens. Throughout the trial, participants undergo multiple assessments including scans, blood, urine, heart, and lung tests. Safety and tumor response are monitored over time, with primary outcomes measured at 6 and 12 weeks post-infusion and at regular intervals thereafter. Participants are followed for up to two years with ongoing evaluations and medication to prevent infections. The study may last several years, with long-term monitoring to assess treatment effects and safety.

Researchers are investigating the causes and development of adrenal tumors, which include adrenocortical carcinoma, Cushing syndrome, Conn syndrome, and pheochromocytoma. The study aims to better understand how these tumors form and to evaluate new treatment options for patients with malignant adrenal tumors, addressing the limited current therapies available. This observational research is sponsored by the University of Wuerzburg and has been ongoing since 2002. Participants in the study may provide tumor material and related biological samples if they have adrenal tumors. Additionally, biological samples are collected from patients without adrenal tumors to serve as comparison controls. The research does not involve experimental treatments but focuses on collecting and analyzing biospecimens to explore tumor biology and potential therapies. Throughout the study, participants contribute by providing tumor and biosample materials. Researchers analyze these samples to study tumor characteristics and evaluate possible new treatments. There are no specific outcome measures listed. The study is observational, with no assigned treatments, and aims to gather information to support future therapeutic developments. Participants involvement duration varies, and the study is expected to continue until December 2032.

Researchers are evaluating the tissue-agnostic effectiveness of the anti-PD1 antibody nivolumab in patients with advanced or metastatic rare tumors that express PD-L1 with a combined positive score of 10 or higher. This phase II basket trial includes patients whose cancers have progressed despite standard treatments. Rare tumors, defined by low incidence rates, collectively represent a significant portion of cancers with generally poor prognosis and limited clinical trial representation. Participants receive intravenous nivolumab at a dose of 480 mg every 4 weeks, continuing until disease progression, limiting toxicity, or for up to 12 months if responses are stable or improving. After treatment ends or discontinuation, patients are followed by phone every 60 days until death. This innovative approach targets the molecular characteristic PD-L1 regardless of tumor origin, aiming to provide new therapeutic options across many rare cancer types. During the study, researchers assess tumor response using RECIST v1.1 criteria and monitor biomarkers including PD-L1 expression, circulating tumor DNA, and microvesicles to understand treatment effects. Patients undergo regular evaluations to measure objective response and progression-free survival. Safety is closely monitored throughout the treatment and follow-up periods. The study is conducted across multiple centers to overcome challenges in rare cancer research and is expected to last about four years.