Clinical Research Directory

Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma

The I-MAT trial is a randomised, placebo-controlled, phase II trial of adjuvant Avelumab in patients with stage I-III Merkel cell carcinoma aiming to explore the efficacy of avelumab as adjuvant immunotherapy.

Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer

Background: A person s tumor is studied for mutations. When cells are found that can attack the mutation in a person s tumor, the genes from those cells are studied to find the parts that make the attack possible. White blood cells are then taken from the person s body, and the gene transfer occurs in a laboratory. A type of virus is used to transfer the genes that make those white blood cells able to attack the mutation in the tumor. The gene transfer therapy is the return of those white blood cells back to the person. Objective: To see if gene transfer therapy of white blood cells can shrink tumors. Eligibility: People with certain metastatic cancer for which standard treatments have not worked. Design: Participants may complete screening under another protocol. Screening includes: * Getting tumor cells from a previous procedure * Medical history * Physical exam * Scans * Blood, urine, heart, and lung tests The study has 8 stages: 1. Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm. 2. Care at home over approximately 12 weeks. 3. Stopping therapy for 4-6 weeks while their cells are changed in a lab. 4. Hospital stay approximately 3-4 weeks for treatment. An IV catheter will be placed in the chest to administer drugs. 5. Patients on Arm 2 of the study will receive the first dose of pembrolizumab while in the hospital. Three additional doses will be given after the cell infusion 3 weeks apart. 6. Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer. 7. Recover in the hospital for 1-2 weeks. Participants will get drugs and have blood and urine tests. 8. Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined. ...

Follow Up Protocol for Subjects Previously Enrolled on NCI Surgery Branch Studies

Background: The NCI Surgery Branch has developed experimental therapies that involve taking white blood cells from participants' tumor or from their blood, growing them in the laboratory in large numbers, and then giving the cells back to the patient. Objective: This study will allow participants to be followed for up to 15 years following treatment on an NCI Surgery Branch Gene Therapy Trial as required by the FDA. Eligibility: Participants must have been enrolled on an NCI Surgery Branch Gene Therapy Protocol Design Participants will be followed with a physical examination and blood tests for up to 15 years as required by the FDA

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.

Targeted Alpha-emitter Therapy of PRRT Naïve and Previous PRRT Neuroendocrine Tumor Patients

Multicenter Phase 2 study of 212Pb-DOTAMTATE enrolling adult subjects with positive somatostatin positive neuroendocrine tumors with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT)

Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients

The purpose of the study is to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide compared to targeted molecular therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).

Study of Cabozantinib in Participants With Neuroendocrine Tumors Who Have Already Received Prior Treatment

This study will assess how well cabozantinib works and how safe it is in adults with a type of cancer called neuroendocrine tumors (NETs). These tumors can appear in all parts of the body. All participants in this study have already received at least one treatment that affects the whole body to help manage their cancer, but their disease has continued to grow. The study will take place in regular hospitals and clinics in Germany and Austria. It will follow about 150 participants who are taking cabozantinib as part of their usual care. Doctors will collect information from routine medical visits, tests, and scans to see how the cancer responds to treatment and how long participants stay on cabozantinib. They will also look at side effects and how the treatment affects participants' quality of life. This is an observational study, which means that no extra tests or procedures will be done beyond what is normally used to care for participants with this condition.

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.

Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity \[HA\]-DOTATATE.

A First-in-Human Phase I Trial With Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors, Carcinomas and Malignant Peripheral Nerve Sheath Tumors

Background: Neuroendocrine neoplasms (NENs) are rare cancers in the gastrointestinal tract, pancreas, lungs, adrenal glands, and other areas of the body. Many of these cancers have a high risk of relapse and a low chance of survival. Better treatments are needed. Objective: To test a new drug, ADCT-701, in people with NENs. Eligibility: Adults aged 18 and older with NENs. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of heart functioning. Their ability to perform normal daily activities will be tested. A biopsy may be needed: A sample of tissue will be removed from the tumor. ADCT-701 is given through a tube attached to a needle inserted into a vein in the arm. Participants will receive the drug treatment on the first day of 21-day treatment cycles. They will visit the clinic a total of 10 times during the first two cycles. After that, they will visit the clinic 2 times during each cycle. Imaging scans, blood draws, heart function tests, and other tests will be repeated during study visits. Each visit will last up to 8 hours. Participants may continue receiving treatment with the study drug for up to 2 years. After treatment ends, participants will have follow-up clinic visits 4 times in 4 months. They will have a physical exam, with heart and blood tests, at each visit. After that, they will have follow-up clinic visits every 9 weeks; these visits will include imaging scans. Follow-up visits will continue for up to 5 years after treatment began....

Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease with a high degree of penetrance (\>80% of patients). It is caused by the presence of the MEN1 mutation located on chromosome 11q13. The prevalence of this mutation is estimated at approximately 1/30,000. This hereditary syndrome is characterized by the presence of tumours of the endocrine system (adenoma of the parathyroid, pituitary and adrenal glands, neuroendocrine tumors - NETs - of the endocrine pancreas, duodenum, lung or thymus), which threaten the health of these patients. Other malignant tumors such as breast cancer are also more common in patients with MEN1. The clinical manifestations of MEN1 are linked to the location of the adenomas and NETs and their secretory products. Indeed, most NETs produce and secrete numerous peptide hormones (in the case of Insulinomas, Gastrinomas, VIPomas, Glucagonomas or PPomas for example). This causes a specific clinical syndrome, which can be detected in the blood serum. However, most NETs are "non-functional" tumors, which do not have specific secretions. Among general tumor markers, chromogranin A (CgA) is widely used as a biomarker for monitoring NETs. CgA is a secretory protein released into the blood by neuroendocrine cells. However, the performance of CgA as a diagnostic biomarker is too limited to be used for the early identification of NETs, particularly in patients with MEN1. This is why patients with MEN1 undergo regular biological and morphological examinations, at least once a year, to screen for the development of adenomas and NETs. However, CgA or hormone secretions assays, and imaging examinations (MRI, CT scan, or duodenopancratic endoscopic ultrasound (EUS)) are tedious and stressful for patients; in addition, they all have their limitations (poor performance for biological tests; irradiation for CT scan; need for anesthesia for endoscopic ultrasound, etc.). Consequently, there is a need for new markers to identify NETs in this population as early as possible. Progastrin is a pro-hormone that, under physiological conditions, is matured into gastrin in the G cells of the antrum of the stomach. The role of gastrin is to stimulate gastric acid secretion during digestion. It also plays an important role in regulating cell growth in the gastric mucosa. In pathological situations, it has been shown that the GAST gene, which codes for progastrin, is over-expressed in human tumor cells of different origins, leading to the accumulation of progastrin within them. Tumor cells that are unable to mature progastrin into gastrin, either because the maturation enzymes are not expressed or are inhibited, will secrete it. This circulating progastrin is then called hPG80 (to differentiate it from intracellular progastrin) and is detectable in patient blood. hPG80 is a new biomarker for the detection of different types of cancer. It appears to be elevated in the early stages of the disease, potentially more so than other biomarkers such as circulating tumor DNA (ctDNA) or NETest. In addition, hPG80 is easily measured in plasma using the DxPG80.Lab ELISA (Progastrin Manufacturing). The analytical characteristics of this CE-marked in vitro diagnostic test have been published in the Analytical Methods journal. It has been validated in numerous studies of various cancers, including NET patients. In addition, a study conducted by the team at Progastrin Manufacturing (formerly ECS-Progastrin) showed that hPG80 was unequivocally present in the peripheral blood of patients with 11 different types of cancer, with a concentration significantly higher than that found in blood donors considered to be healthy. We therefore hypothesize that hPG80 could also be a biomarker for NETs in MEN1.

Dual Tracer (68Ga-DOTATATE and 18F-FDG) PET Imaging in G2 & G3 Gastroenteropancreatic Neuroendocrine Tumors

The variable clinical outcome of patients with G2 \& G3 well diff GEP-NETs makes the selection of an optimal treatment strategy challenging. Initial data suggests that high DOTATATE uptake and low FDG uptake are suggestive of low grade disease, with an indolent course. Conversely, low DT uptake and high FDG uptake are suggestive of high-grade/ aggressive disease. G2/3 GEP NETs may be biologically diverse; clinically relevant cohort for dual-tracer PET imaging. Our secondary objectives are 1. To determine the distribution of PETNET scores derived from 18F-FDG \& 68Ga-DT PET in patients with G2 \& G3 well diff GEP-NETs. 2. To determine the proportion of patients in whom the addition of 18F-FDG PET data results in a change in planned clinical management. To assess intra-individual variability in SSTR expression \& glucose metabolism (as seen on DT and FDG PET) across different tumor sites within the same patient. 2\) To determine whether a correlation exists between tumor texture features on 68Ga-DT \& FDG PET to tumor grade and Ki 67 index. 3\) To assess for an association between tumor texture features on 68Ga-DT PET and glucose metabolism; and/or an association between tumor texture features on FDG PET and SSTR expression.

Peptide Receptor Radionuclide Therapy (PRRT) for the Treatment of Neuroendocrine Tumors

The specific aim is of this study is to gain a better understanding of the patient characteristics, treatment responses, survival outcomes, and adverse events associated with PRRT in patients with gastroenteropancreatic primary NETs.

Using Novel Imaging to More Safely Treat Neuroendocrine Tumors

The goal of this research is to determine if DetectnetTM PET/CT can be used to make Lutathera therapy safer for patients with neuroendocrine cancer. Participants will: * Complete two phases involving 6 visits * Undergo additional research PET/CT, and possibly SPECT/CT scans

Assessment of Compliance With Monitoring Conducted by a Physician in Person or by a Nurse in Remote Monitoring

This is a multicenter, interventional, randomized study among adult patients recently diagnosed with a rare tumor (\<12 months). The study will aim to compare compliance with the personalized post-treatment surveillance plan, established for each patient according to national guidelines, when the surveillance is conducted in person by a hospital-based physician (control arm) or remotely by a trained nurse (experimental arm).

Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors

This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.

Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors

This is the first study to be done in a newly described class of neuroendocrine tumors known as well-differentiated grade 3 neuroendocrine tumors (WD G3 NET). First described in the pancreas in 2017, the classification was broadened to include gastrointestinal tract tumors in 2019. Recent data suggest an equivalent subtype exists in the lungs (NEC with carcinoid morphology). WD G3 NETs can occur de novo as well as the result of grade progression over time. This is a single arm, multi-site, Phase II study in biomarker "unselected" participants. This study will also incorporate serial blood samples, tumor biopsies, and special imaging to better understand the impact of therapy on the tumor and microenvironment. Hyperpolarized (HP) 13C-pyruvate magnetic resonance imaging (MRI) - a novel non-radioactive imaging modality able to provide in vivo measurements of the pyruvate-to-lactate conversion rate (kpl).

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.

A Pilot Study of Total-body PET Using FDA-approved Radiotracers Beyond 18F-FDG

The purpose of this research study is to test new ways to improve the usefulness of the world's first total-body positron emission tomography (PET)/computed tomography (CT) scanner (EXPLORER) by collecting data from PET scans using one of three different imaging agents: 18F-PSMA; 18F-FES; or, 68Ga DOTATATE. These imaging agents are approved by the FDA to be used for patients diagnosed with prostate cancer (18F-PSMA), neuroendocrine tumor (68Ga DOTATATE), or breast cancer (18F-FES).

Defining Response Criteria for PET Scans for People With Neuroendocrine Tumors

People with neuroendocrine cancer typically have imaging scans before and after treatment, including positron emission tomography (PET) scans. The scans are analyzed using a set of criteria that describes how the disease has responded to treatment. The purpose of this study is to establish new criteria for doctors to use when evaluating these PET scans. Researchers are testing whether these new criteria are useful for predicting whether a person's cancer gets better, gets worse, or stays the same. Researchers will also compare these new criteria to the current standard criteria for evaluating imaging scans.

Efficacy and Safety of Radiotherapy Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.

LEVEL trial aims to demonstrate the higher efficacy of 177Lu-edotreotide over everolimus in patients with well to moderately differentiated neuroendocrine tumors of the lung and thymus who require systemic therapy. It is hypothesized that 177Lu-edotreotide may significantly increase the progression-free survival (PFS) compared to everolimus in lung and thymic carcinoids.

Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)

This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene fusion. Patients will be assigned to different baskets according to tumor type and gene fusion.

CardioNETPOL National Registry of Carcinoid Heart Disease

Carcinoid tumors are neuroendocrine tumors (NETs), most commonly originating from the gastrointestinal tract, that may secrete bioactive substances such as serotonin. Persistent exposure to these mediators can lead to carcinoid syndrome and, in up to 50% of patients, carcinoid heart disease (CHD). CHD is characterized by fibrotic degeneration of cardiac valves, predominantly right-sided, resulting in progressive valvular dysfunction and a significant increase in mortality. The mechanisms underlying selective cardiac involvement and predictors of disease progression remain incompletely understood. In addition, optimal timing and selection of surgical versus transcatheter valve interventions, particularly in high-risk patients, require further clarification. This multicenter, retrospective observational registry aims to identify and characterize patients with carcinoid heart disease and at least moderate valvular involvement. CHD is defined by confirmed neuroendocrine tumor, echocardiographic evidence of ≥ moderate valvular disease with features of fibrosis, elevated NT-proBNP (\>260 ng/L), and histopathological confirmation when available. Approximately 100-120 consecutive patients will be enrolled over 12 months. Standardized data collection will include detailed echocardiographic assessment, demographic and clinical characteristics, cardiovascular risk factors, comorbidities, tumor features, oncological treatment history, and cardiac management strategies. The primary objective is to describe the clinical profile and management of patients with CHD in a real-world multicenter setting. Secondary objectives include identifying factors associated with advanced valvular dysfunction and evaluating eligibility and outcomes of transcatheter valve therapies. The registry is expected to improve risk stratification and support clinical decision-making in carcinoid heart disease.

Combination Immunotherapy in Rare Cancers Under InvesTigation

The four tumour streams that will be studied in this protocol are based on immunotherapy sensitive rare cancers from CA209-538 which will be further investigated under this protocol and divided into four groups: 1. Neuroendocrine cancers: Atypical bronchial carcinoid, neuroendocrine carcinoma and Grade 3 NETs independent of primary site (SCLC excluded) 2. Biliary tract cancers: Intrahepatic cholangiocarcinoma and gallbladder carcinoma 3. Gynaecological malignancies: Ovarian clear cell carcinoma, uterine clear cell carcinoma, uterine/ovarian carcinosarcoma, uterine leiomyosarcoma and vaginal/vulva squamous cell carcinoma 4. Mismatch repair protein deficient (MSI-H) cancers (excluding colorectal carcinoma). The role of immunotherapy is being defined in more common cancer types, however because of their rarity, the efficacy of immunotherapy for these cancers is poorly defined. This protocol provides an important opportunity to establish whether the combination of nivolumab \& ipilimumab has efficacy in these cancers.