Clinical Research Directory

Lu-177-DOTATATE (Lutathera) in Combination With Olaparib in Inoperable Gastroenteropancreatico Neuroendocrine Tumors (GEP-NET)

Background: A neuroendocrine tumor is a rare type of tumor. It comes from body cells called neuroendocrine cells. Sometimes, these tumors develop in the gastrointestinal tract and pancreas. Researchers want to find out if a combination of drugs can shrink these tumors. Objective: To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects, and if this treatment makes the tumors shrink. Eligibility: Adults 18 and older who have a neuroendocrine tumor in the pancreas or intestine that cannot be cured by surgery and has somatostatin receptors on the cells. Design: Eligible participants will get Lutathera through an intravenous (IV) infusion every 8 weeks for 4 cycles. One cycle is 8 weeks. Each cycle includes a follow-up visit at week 4. For the IV, a small plastic tube is put into an arm vein. Participants will also take Olaparib by mouth twice a day for 4 weeks of each cycle. They will use a medicine diary to track the doses. During the study, participants will have physical exams. They will have blood and urine tests. They will fill out questionnaires about their general well-being and function. Their heart function will be tested. They will have scans of their chest, abdomen, and pelvis. One type of scan will use an IV infusion of a radioactive tracer. Participants will have a follow-up visit about 4 weeks after treatment ends. Then they will have follow-up visits every 12 weeks for 3 years. Then they will have yearly phone calls.

A Study to Test How Well Different Doses of Obrixtamig (BI 764532) in Combination With Ezabenlimab Are Tolerated by People With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3

This study is open to adults with small cell lung cancer and other neuroendocrine tumours that are positive for the tumour marker Delta-like 3 (DLL3). The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find out the highest dose of obrixtamig that people can tolerate when taken together with another medicine called ezabenlimab. Obrixtamig and ezabenlimab may help the immune system fight cancer. Participants get obrixtamig and ezabenlimab as infusions into a vein. If there is benefit for the participants and if they can tolerate it, the treatment is given for a maximum of 3 years. During this time, participants visit the study site about every week. The visits also depend on the response to the treatment. At the study visits, the doctors check the health of the participants, take necessary laboratory tests, and note any health problems that could have been caused by the study treatment.

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

Background: Pheochromocytoma and paraganglioma are rare tumors. They usually form inside and near the adrenal gland or in the neck region. Not all these tumors can be removed with surgery, and there are no good treatments if the disease has spread. Researchers think a new drug may be able to help. Objective: To learn the safety and tolerability of Lu-177-DOTATATE. Also, to see if it improves the length of time it takes for the cancer to return. Eligibility: Adults who have an inoperable tumor of the study cancer that can be detected with Ga-68-DOTATATE PET/CT imaging Design: Participants will be screened with a medical history, physical exam, and blood tests. Eligible participants will be admitted to the NIH Clinical Center. Participants will get the study drug in an intravenous infusion. They will get 4 doses, given about 8 weeks apart. Between 4 and 24 hours after each study drug dose, participants will have scans taken. They will lie on their back on a scanner table. Participants will have vital signs taken. They will give blood and urine samples. During the study, participants will have other scans taken. Some scans will use a radioactive tracer. Participants will complete quality of life questionnaires. Participants will be contacted by phone 1-3 days after they leave the Clinical Center. They will then be followed every 3 to 6 months for 3 years or until their disease gets worse.

DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers

This study is open to adults with small cell lung cancer and other neuroendocrine tumours. The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find a suitable dose of BI 764532 that people with advanced cancer can tolerate. 2 different doses of BI 764532 are tested in this study. Another purpose is to check whether BI 764532 can make tumours shrink. BI 764532 is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. The study has 2 parts. In Part 1, participants are put into 2 groups randomly, which means by chance. Participants have an equal chance of being in either group. One group gets dose 1 of BI 764532 and the other group gets dose 2 of BI 764532. In Part 2, all participants receive the same dose of BI 764532. Part 2 is open to people with a certain kind of tumour called extrapulmonary neuroendocrine carcinoma. All participants receive BI 764532 as an infusion into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is given up to the maximum duration of the study. During this time, participants visit the study site regularly. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include an overnight stay to monitor participants´ safety. Doctors record any unwanted effects and regularly check the general health of the participants.

Prospective Multicenter Real-world Study of Surufatinib in Patients With Advanced Neuroendocrine Neoplasms

This is a prospective, multicenter, phase 4, single-arm study designed to evaluate the effectiveness and safety of surufatinib in adult patients with advanced neuroendocrine neoplasms (NENs) treated in routine clinical practice. Approximately 350 patients with histologically or cytologically confirmed advanced NENs and at least one measurable lesion (RECIST 1.1) will receive oral surufatinib, either as monotherapy (300 mg once daily in 4-week cycles) or in combination regimens (250 mg once daily), according to the treating physician's judgment and protocol guidance. Participants will be followed with regular imaging, laboratory tests, cardiac assessments, and patient-reported outcome questionnaires to monitor tumor response, side effects, quality of life, and treatment adherence. The primary outcomes include progression-free survival, objective response rate, disease control rate, and overall survival; safety will be assessed by the type, frequency, and severity of adverse events. The findings are expected to inform standardized, evidence-based use of surufatinib and help optimize individualized treatment strategies for patients with advanced NENs in the real-world setting.

DAREON™-7: A Study to Test How Well Different Doses of BI 764532 in Addition to Chemotherapy Are Tolerated by People With Advanced Neuroendocrine Cancers

This study is open to adults aged 18 and older or above legal age who have a specific type of advanced neuroendocrine cancer (NEC). Their tumours must be positive for a marker called DLL3. The purpose of this study is to test a medicine called BI 764532 in addition to chemotherapy. The study has Part A1, Part A2, and Part B. Part A1 of this study aims to find out the highest dose of BI 764532 that people can tolerate in addition to chemotherapy. Part A2 of this study is to find out how well people tolerate a low dose of BI 764532 combined with the chemotherapy. The purpose of Part B is to find out how well people can tolerate BI 764532 in combination with different chemotherapies. Researchers also want to find out whether BI 764532 in combination with chemotherapy helps people with NEC. Participants get different doses of BI 764532 as an infusion into a vein. In addition, they get platinum-based chemotherapy as infusions into a vein. Participants can continue treatment up to 3 years if they benefit from treatment and can tolerate it. Participants visit their doctors regularly. During these visits, the doctors collect information about participants' health and take note of any unwanted effects. Doctors also regularly check the size of the tumour.

A Study to Test How BI 764532 is Taken up by Tumours in People With Small-cell Lung Cancer or Neuroendocrine Cancer

This study is open to adults with small cell lung cancer and other neuroendocrine cancers. The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find out how a medicine called BI 764532 gets distributed in the body and in tumours. Participants get BI 764532 when starting treatment. In the first weeks, doctors check how BI 764532 is taken up in tumours by means of an imaging method. If there is benefit for the participants and if they can tolerate it, the treatment is given up to the maximum duration of the study. During this time, participants visit the study site regularly. The total number of visits depends on how they respond to and tolerate the treatment. Doctors record any unwanted effects and regularly check the general health of the participants.

Collection of Liquid Biopsy Samples of Neuroendocrine Neoplasms (NEN) Patients - Collection of NET (CollectNET) 2.0, a Study by the BE-FORCE Consortium

The CollectNET 2.0 by BE-FORCE is a prospective, multicentric, interventional study in which liquid biopsies will be collected from neuroendocrine neoplasms (NEN) patients to create an extensive biobank that will be used for current and future circulating cell-free DNA (ccfDNA) analyses. Two sampling groups will be created: the "Regular Sampling Group" and the "Intensive Sampling Group". Upon participation, up to four additional blood tubes (max. total of 32.5mL) will be collected at each timepoint as specified below. These include 3 Streck Cell-Free DNA tubes (10 mL each) which will be used for the extraction of ccfDNA and 1 PreAnalytiX (PAXgene)® Blood RNA tube (2.5 mL). All NEN patients in one of the participating hospitals who have measurable tumor burden on imaging will be asked to participate in our study and will be included in the "Regular Sampling Group". If additionally, the patient is (i) diagnosed with a histologically confirmed NEN of World Health Organisation (WHO) 2019 grade 1-3 neuroendocrine tumor (NET) or neuroendocrine carcinoma (NEC) from pancreatic, colorectal or small intestinal origin and (ii) is starting any kind of 1st line systemic treatment (e.g. somatostatin analogues, targeted therapy, chemotherapy, etc.), they will be followed up more intensively as per the "Intensive Sampling Group". If during follow-up in this "Intensive Sampling Group" patients have disease progression or have completed follow-up for 3 years in this group, their follow-up will switch back to the "Regular Sampling Group" for the remainder of the study. Ultimately, the samples collected in the "Intensive Sampling Group" will be used to achieve the second and third objective of our current project. These are to validate novel ccfDNA analyzing techniques (IMPRESS and GIPXplore) for assessment of the presence and quantification of circular tumor DNA (ctDNA) in liquid biopsies, and to monitor tumor fraction (i.e., ctDNA quantities) over time in sequential plasma samples from NEN patients using ccfDNA assays and correlating this with time to progression (according to RECIST 1.1 criteria) to explore the predictive efficacy of ccfDNA analysis and thereby evaluate its biomarker potential for patient follow-up. While samples from the "Regular Sampling Group" and the PAXgene tubes will be biobanked for future projects.