Clinical Research Directory

Use of Tracking Devices to Locate Abnormalities During Invasive Procedures

This study will evaluate the accuracy and effectiveness of an experimental tracking device for locating abnormalities during invasive procedures, such as biopsy or ablation, that cannot easily be visualized by usual imaging techniques, such as computed tomography (CT) scans or ultrasound. Some lesions, such as certain liver or kidney tumors, small endocrine abnormalities, and others, may be hard to find or only visible for a few seconds. The new method uses a needle with a miniature tracking device buried inside the metal that tells where the tip of the needle is located, somewhat like a mini GPS, or global positioning system. It uses a very weak magnet to localize the device like a miniature satellite system. This study will explore whether this system can be used in the future to more accurately place the needle in or near the desired location or abnormality. Patients 18 years of age and older who have a lesion that needs to be biopsied or an ablation procedure that requires CT guidance may be eligible for this study. Candidates are screened with a medical history and review of medical records, including imaging studies. Participants undergo the biopsy or ablation procedure as they normally would, with the following exceptions: some stickers are placed on the skin before the procedure and a very weak magnet is placed nearby. The needles used are similar to the ones that would normally be used except that they contain a metal coil or spring buried deep within the needle metal. The procedure involves the following steps: 1. Small 1-cm plastic donuts are place on the skin with tape. 2. A planning CT scan is done. 3. The CT scan is sent to the computer and matched to the patient's body location with the help of a very weak magnet. 4. The needle used for the procedure is placed towards the target tissue or abnormality and the "smart needle" location lights up on the old CT scan. 5. A repeat CT is done as it normally is to look for the location of the needle. 6. After the procedure the CT scans are examined to determine how well the new tool located the needle in the old scan.

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

PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer

This is an international, multicenter and randomized open-label phase III study designed to demonstrate, in patients with stage IIIC1 cervical cancer, whether para-aortic lymphadenectomy followed by tailored chemoradiation is associated with increased disease-free survival compared to patients staged with FDG-PET/CT only followed by chemoradiation. The planned sample size is 510; including 200 patients in France. In this trial, patients will be assigned in one of the two following treatments arms: * Arm A (control arm): Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations. * Arm B (experimental arm): Pretherapeutic para-aortic lymphadenectomy followed by tailored chemo-radiotherapy and brachytherapy. Considering the changing standard treatment landscape of locally advanced cervical cancer, both arms (control arm and experimental arm) may also be treated according to the INTERLACE and KEYNOTE-A18 studies, if applicable, at the discretion of the attending physician. Each patient will be followed up for 5 years. A cost-utility study will be performed in patients included in France. Other countries could be involved in this specific study. It will assess the incremental cost-utility ratio (cost per QALY gained) of para-aortic lymphadenectomy followed by tailored chemo-radiation in patients with positive PALN compared to patients staged with PET/CT only followed by chemo-radiation. This study also has ancillary objectives: * Biologic: To study T cell exhaustion, immune changes during chemoradiation, HPV ctDNA dynamic evolution, and the par-aortic lymph node as a premetastatic niche. * Radiomics: To study the contribution of radiomics and FDG-PET/CT metabolic parameters to predict para-aortic lymph node involvement and clinical outcome. * Senti-PAROLA: To evaluate the accuracy (Sensitivity, specificity, positive and negative predictive value) of the para-aortic sentinel lymph node (SPA) for PALN staging, and to evaluate the prognostic value of low volume metastasis of SPA.

Relacorilant With Nab-Paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

This is a Phase 2, single-arm study to evaluate the safety and efficacy of relacorilant in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic pancreatic adenocarcinoma (PDAC).

T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe. Eligibility: \- Adults age 18-72 with NSCLC who have a tumor that can be safely removed. Design: * Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. * Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Anatomical-Clinical Base of Adenocarcinoma Pancreatic

BACAP-2 is a prospective biobank dedicated to the pancreatic adenocarcinoma including clinical data and biological samples from tumor. The aim is to enrich the previous propective collection BACAP in order to support future research projects.

Using a PET Imaging Agent, 18F-Clofarabine (CFA), to Measure Deoxycytidine Kinase Activity in Metastatic Cancer

The purpose of this study is to evaluate whether a new type of imaging study, called 18F-Clofarabine (CFA) PET/CT, can be used to image cancer pyrimidine metabolism in participants. PET (positron emission tomography) imaging is a way of looking at cancers that can reveal cancer metabolism. Presently, however, there are no imaging agents in routine use to look at an aspect of cancer metabolism (pyrimidine metabolism) that dictates whether certain cancer drugs, e.g., gemcitabine, are likely to be taken into the cancer cells. This clinical trial will be testing whether 18F-Clofarabine (CFA) could be an imaging agent to measure this aspect of cancer metabolism.

A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) of JNJ-69086420 in Part 1 (Dose Escalation), to determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion), to determine safety of JNJ-69086420 at the RP2D(s) as a combination therapy in Part 3 (combination therapy) and to determine safety of JNJ-69086420 at the RP2D(s) in participants with metastatic hormone-sensitive prostate cancer (mHSPC) in Part 4.

Prospective Data Collection Initiative on Thoracic Malignancies

Survival after cancer diagnosis strongly depends on local tumor extent, lymph node involvement and the presence of distant metastases. However, there remains great inter-patient variability regarding treatment outcome. A combination of molecular factors, biochemical factors, histopathological features, genomic profile, environmental factors and other clinical factors are likely to influence prognosis and treatment effect, independent from tumor stage. It is however still unclear which, how, and to what extent these factors will influence tumor recurrence and mortality in both early stage (I-III) and late stage (IV) thoracic malignancies such as lung cancer. Although the results from prospective clinical trials will remain the backbone of evidence-based medicine, this concerns a highly selected patient population since the large majority (85%-95%) of patients with cancer do not participate in clinical trials for various reasons. It is unlikely that trial participation will significantly improve in the near future. This fact has the following implications: 1. It is highly desirable to validate the results from clinical trials in the general patient population. This is complicated by the fact that the documentation of patients treated in general practice (i.e. outside the scope of clinical trials) is largely insufficient to provide comparable patient cohorts in terms of prognostic characteristics and treatment parameters. 2. There is an ever increasing number of therapeutic interventions available for which its efficacy depends on known and unknown tumor-specific, clinical, demographic and other patient characteristics. Large numbers of patients are required to test the relevance of these variables. 3. As a result of rapid technical and drug developments, new minimally invasive treatment options such as stereotactic irradiation or ablation techniques or sublobar resections and new targeted and immunotherapeutic treatments have entered the clinic. These interventions have potentially less side effects compared to the conventional treatments. Still, these new interventions will have to prove their effectiveness, safety and superiority (or non-inferiority) in a real world setting. 4. Many hypotheses related to further optimization of personalized medicine can currently not be tested as they require a large prospective cohort of patients, and a less time-consuming and costly research infrastructure. A prospective observational cohort study has the potential to fill the gap between prospective randomized trials (efficacy) and patients treated in general practice (effectiveness) and it will enable accrual of clinical trials (innovation).

Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells Delivered Intraperitoneally for the Management of Platinum Resistant Ovarian Cancer, Mesonephric-like Adenocarcinoma, and Pancreatic Cancer

To find the recommended dose of TROP2- CAR-NK given intraperitoneally (directly into the abdominal cavity) to patients with highgrade serous ovarian cancer that has not responded to previous treatment or is resistant to treatment.

Clinical Study on the Efficacy and Safety of LM-302 Injection Combined With Tislelizumab and Tislelizumab Combined Chemotherapy for the Treatment of Gastric or Gastroesophageal Junction Adenocarcinoma.

This study primarily evaluates the efficacy and safety of the LM-302 plus tislelizumab regimen versus tislelizumab plus chemotherapy in the treatment of previously untreated locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma patients with CLDN18.2 positivity.

A Pilot Study to Assess Changes in Tumor Biology Following Second-line Treatment With Pembrolizumab Plus Lenvatinib in Patients With Advanced Pancreatic Ductal Adenocarcinoma

This is a clinical research study to learn if pembrolizumab in combination with lenvatinib can help to control pancreatic ductal adenocarcinoma.

Clinical, Genetic and Environmental Determinants of Prostate Cancer Progression.

The course and progression of prostate cancer is highly variable, depending on the individual characteristics, the aggressiveness of the disease at the time of diagnosis as well as the ethno-geographic origins of the individuals. The general objective of the project is to identify the clinical, genetic and environmental determinants (risk factors) of the evolution, progression and complications of the disease according to the treatment options. Identifying modifiable and non-modifiable prognostic determinants of disease progression is a major challenge. This knowledge will help guide treatment choices but also, especially in high-risk populations (high incidence of disease) to better tailor prevention policies and possibly screening .

Safety of Combining Irinotecan With 5-FU, Leucovorin/Folinic Acid, Oxaliplatin, and Docetaxel Chemotherapies

The purpose of the proposed study is to establish the safety of combining irinotecan chemotherapy with 5-FU, leucovorin/folinic acid, oxaliplatin, and docetaxel (abbreviated as the I-FLOAT study of gFOLFOXIRITAX) chemotherapies (leucovorin/folinic acid is a vitamin to make 5-FU work well).

Efficacy and Safety of Multimodal Ablation Combined With PD-1 Monoclonal Antibody, Lenvatinib and TACE in the Treatment of Unresectable Primary Hepatocellular Carcinoma: A Single-Arm, Single-Center Clinical Study

This study is a prospective, single-arm, single-center trial evaluating the efficacy of TACE combined with multimodal ablation, Tislelizumab, and lenvatinib in the treatment of unresectable primary liver cancer.

Novel SEQUEnced Immunotherapy With Anti-angiogenesis and Chemotherapy in Advanced gastroesophageaL Adenocarcinoma

Cohort 1 \[CLOSED\] Study treatment involves two segments: (1) Induction Immunotherapy segment with pembrolizumab monotherapy every 3 weeks until irRECIST PD and (2) Combination Therapy segment. Nab-paclitaxel may be utilized in place of paclitaxel at investigator's discretion for subjects with paclitaxel reactions. Cohort 2 Patients are randomized to Arm A or B. Treatment in both arms includes pembrolizumab + RAM + paclitaxel.

Imperial Prostate 7 - Prostate Assessment Using Comparative Interventions - Fast Mri and Image-fusion for Cancer

To evaluate the role of biparametric MRI and image-fusion targeted biopsies for the detection of prostate cancer. To determine whether biparametric MRI (bpMRI) could be recommended as an alternative to multiparametric MRI (mpMRI) for the detection of clinically significant prostate cancers in patients at risk. To determine whether image-fusion targeted biopsy is better than visual-registration (cognitive) targeted biopsy at detecting clinically significant prostate cancers in patients requiring prostate biopsy due to a suspicious MRI.

Chemo4METPANC Combination Chemokine Inhibitor, Immunotherapy, and Chemotherapy in Pancreatic Adenocarcinoma

The purpose of this study is to determine if combination treatment with cemiplimab, motixafortide, gemcitabine, and nab-paclitaxel is effective in decreasing the size of the tumor(s), if it will prolong life in patients, and if it's safe. The treatment consists of standard chemotherapy (gemcitabine and nab-paclitaxel) which is FDA approved and is standard treatment for patients with pancreatic adenocarcinoma. Participants will receive immunotherapy (cemiplimab) which activates the body's immune system to attack cancer cells. Cemiplimab is FDA approved for treatment of skin cancer but not for pancreas cancer. Participants will also receive Motixafortide, a new medication which has shown in the laboratory to help immunotherapy work better. Motixafortide has been tested together with immunotherapy (Pembrolizumab), and chemotherapy (5-Fluorouracil and liposomal Irinotecan) and was deemed safe to test additional patients. Motixafortide has not been tested with the specific immunotherapy (Cemiplimab) and chemotherapy (gemcitabine and nab-paclitaxel) which participants will receive and is being tested in this clinical trial.

Dose Escalation Study Using Ultra-Hypofractionated, Image-Guided, Intensity-Modulated Radiotherapy in Prostate Cancer

The purpose of this study is to test the safety of a new type of IG-IMRT called "ultra-hypofractionated IG-IMRT" where a higher dose of radiation is given to the tumor during each treatment day. Since higher doses of radiation are used each day, the total number of treatment days needed to complete this type of radiation is only five instead of the 45-48 treatments currently used. Treatment takes place every other day and is complete after 2 weeks. If the patient decides to get this treatment, they will come in for 5 treatments. This is different from the 48 treatments they would get normally.

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer

The trial consists of a series of parallel multi-centre single arm phase II trial arms, each testing an experimental targeted drug in a population stratified by multiple pre-specified actionable target putative biomarkers. The primary objective is to evaluate whether there is a signal of activity in each drug-(putative)biomarker cohort separately. A Bayesian adaptive design is adopted to achieve this objective and statistical details are given in the Protocol.

PRIMER: Development of Daily Online Magnetic Resonance Imaging for Magnetic Resonance Image Guided Radiotherapy

In radiotherapy high-tech scans with x-rays (CT scans) are taken before and during treatment to locate the tumour and ensure the radiation is hitting the target. These x-rays expose patients to additional radiation and the quality of these scans is often poor which makes it difficult to distinguish tumour from normal tissue and there may be uncertainty in the tumour position due to movement or shrinkage. To allow for these uncertainties a large margin around the tumour is also treated, but this means that large volumes of normal tissue also receive significant doses of radiation, which can result in early and late toxicity. MRI (magnetic resonance imaging) is better than CT scanning at being able to tell the difference between tumour and normal tissues and does not expose patients to additional radiation. A new machine called an MR Linac (or magnetic resonance imaging-guided linear accelerator) integrates high quality MRI with a state-of-the-art radiotherapy machine and the Institute of Cancer Research (ICR)/The Royal Marsden Hospital (RMH) are currently installation a prototype, which will be one of the first in the world. This revolutionary technology has the potential to change the way radiotherapy is delivered. We hope the improved precision and accuracy in hitting the target will mean reductions in margins around tumours and that this will lead to higher cure rates with significantly fewer side effects. Studies are required to simulate treatment on the MR Linac before it can be used in routine clinical practice and to conduct these studies, we need to obtain MRI scans on volunteers and patients who are currently undergoing treatment. This study will involve imaging with MRI in healthy volunteers as well as in patient volunteers before and during their standard course of radiotherapy to allow us to develop MRI sequences derived on the MR Linac for MR Linac-based research focusing on clinical application and establishment into a MR-CT and MR only workflow, treatment adaptation and quality assurance.

SERum-bank for PANcreatic Cancer

This study is about pancreatic cancer. If the diagnostic cancer is done at an early stage (\<2cm), the chances of recovery are very good. But the main problem is there is not any detections means for this cancer. Sadly, when there is a cancer diagnostic , it's already too late in the majority of cases, because the cancer is in an advanced case. Today, there is no any effective means of detection... Blood markers can be a simple means of early detection

CAR-macrophages for the Treatment of HER2 Overexpressing Solid Tumors

Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.

Evaluation, in Humans, of the Correlation Between Hepatotoxicity, Neurotoxicity Induced by Oxaliplatin, and Blood Levels of HMGB1

Oesogastric and pancreatic adenocarcinomas are poor-prognosis cancers. Incidence of pancreatic cancer drastically increases to such an extent that it will become the second cause of cancer's mortality by 2030. A major challenge is to optimize the therapies for localized setting, when oxaliplatin-based chemotherapy is the standard, before and after surgical excision. Because in 50% of cases oxaliplatin triggers a grade 2-3 sinusoidal obstruction syndrome (SOS) which increases post-operative morbidity, decreases histological response to chemotherapy, increases tumor recurrence, and aggravates the risk of chemotherapy-induced peripheral neuropathy (CIPN). There is an urgent need to better understand the biological processes involved in SOS, in order to prevent and treat it without stopping or reducing oxaliplatin administration. The biological link between oxaliplatin and SOS has not been described, but recent murine experiments argue for HMGB1 to be the mediator released after exposure to oxaliplatin and inducing SOS, and thereafter CIPN. To date, no biomarker is established between murine and patient analyses, and the release of HMGB1 after oxaliplatin treatment and its effect on hepatic parenchyma is not described in patients. Investigators hypothesized is that HMGB1 would also been increased in patients after oxaliplatin treatment, and correlated to the development of SOS and CIPN. If confirmed, personalized treatment will be possible to target this pathway. Therefore, investigators propose to dynamically explore this hypothesis in localized oesogastric and pancreatic cancer patients who will be routinely managed by an initial laparoscopy and post-oxaliplatin surgical excision.