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 therapy's 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 MBq/kg. After 60 minutes, participants will undergo a PET/CT or PET/MR 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 tracer's 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 123I/131I-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 PET/MRI 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 [225Ac]Ac-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 treatment's tolerability. Participants receive [225Ac]Ac-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 kBq/kg to 120 kBq/kg 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 evaluating PM8002, a bispecific antibody targeting PD-L1 and VEGF, in combination with the chemotherapy regimen FOLFIRI as a second-line treatment for patients with neuroendocrine neoplasm (including NEC and Ki-67655% G3 NET) who have not responded to first-line platinum-based chemotherapy. This phase II, single-arm study aims to assess the effectiveness and safety of this combination therapy in this patient group. Participants will receive PM8002 plus FOLFIRI through intravenous infusions every two weeks until their disease progresses or they experience intolerable side effects, for up to a maximum of 2 years. This treatment approach is being studied to understand how well it works and how safe it is for patients with unresectable neuroendocrine neoplasms. During the study, participants will undergo regular evaluations including tumor measurements according to RECIST v1.1 criteria, monitoring of treatment-related adverse events up to 30 days after the last treatment, and assessments of disease control, response duration, progression-free survival, and overall survival for up to approximately 2 years. Organ function and performance status will be monitored to ensure participant safety throughout the trial.

Researchers are evaluating CRN09682 in a Phase 1/2, multicenter, open-label study focused on participants with neuroendocrine neoplasms (NENs) and other solid tumors that express somatostatin receptor type 2 (SST2). The study aims to assess the safety, tolerability, pharmacokinetics (PK), and early antitumor activity of CRN09682. This includes identifying the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in a Dose Escalation Phase, followed by further safety and efficacy assessment at an expansion dose. Participants will receive multiple dose levels of CRN09682 given intravenously every three weeks. The study includes several groups based on tumor type, including pancreatic neuroendocrine tumors, non-pancreatic neuroendocrine tumors, neuroendocrine carcinoma, and other solid tumors. After determining the MTD, additional participants will be enrolled to receive the expansion dose to continue evaluation of safety, tolerability, pharmacokinetics, and antitumor effects. During the study, participants will undergo monitoring for adverse events, dose-limiting toxicities, and pharmacokinetic measurements at Day 1 of each 21-day cycle, continuing up to two years. Researchers will assess tumor response using RECIST 1.1 criteria, somatostatin receptor imaging, and progression-free survival. Safety and tolerability will be closely followed, including assessments of interruptions and serious adverse events. The total participation duration may last approximately two years with regular evaluations throughout.

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 SPECT/CT 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 investigating a gene transfer therapy using a patient's own white blood cells genetically engineered to attack specific mutations in metastatic solid cancers that have not responded to standard treatments. This Phase II study aims to determine if these modified cells, alone or combined with pembrolizumab, can shrink tumors in patients with various cancers including gastrointestinal, genitourinary, breast, ovarian, non-small cell lung cancer, endocrine tumors, neuroendocrine tumors, and multiple myeloma with solid masses. Participants receive a preparative regimen involving cyclophosphamide and fludarabine to prepare the body, followed by an infusion of their own T-cells modified to express T-cell receptors targeting their tumor's neoantigens. Some participants also receive pembrolizumab before and after cell infusion. Treatment includes high- or low-dose aldesleukin to support the infused cells. The study involves hospitalization for treatment and recovery, followed by long-term antibiotic and possible antiviral therapy. During the study, participants undergo extensive screening, including tumor biopsies, scans, blood tests, and physical exams. After treatment, researchers monitor tumor response with imaging and clinical assessments at multiple time points up to two years. Safety and tolerance are also evaluated. Participants are followed closely with regular visits to assess treatment effects, manage side effects, and track disease status.

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.