Clinical Research Directory

Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected

The objective of this study was to evaluate the efficacy and safety of alpelisib in combination with olaparib compared with single-agent cytotoxic chemotherapy in participants with platinum-resistant or platinum-refractory, germline BRCA non-mutated (gBRCAnm) high-grade serous ovarian cancer (HGSOC), with progression-free survival (PFS) as the primary efficacy endpoint.

A Trial to Evaluate Safety, Tolerability, and Preliminary Efficacy of Misetionamide (GP-2250) as Monotherapy or in Combination With Gemcitabine

This is a phase 1 dose escalation trial of monotherapy misetionamide (also known as GP-2250) currently enrolling patients with platinum-resistant ovarian cancer (PROC) into Part 2 of the study. Part 1 of the study evaluating misetionamide in combination with gemcitabine in subjects with advanced pancreatic cancer previously treated with 5-fluorouracil-based chemotherapy completed enrolment.

ADP-A2M4CD8 Monotherapy and in Combination With Nivolumab in HLA-A2+ Subjects With MAGE-A4 Positive Ovarian Cancer (SURPASS-3)

This is a phase 2, open-label, randomized, non-comparative clinical trial to evaluate the clinical outcome of ADP A2M4CD8 as monotherapy and in combination treatment with nivolumab in human leukocyte antigen (HLA) A2+ subjects with recurrent ovarian cancer positive for MAGE-A4.

Video Education With Result Dependent dIsclosure

The overall study objective of this trial study is to identify and evaluate strategies to improve the accessibility of the video education with result dependent disclosure (VERDI) model, increasingly utilized as a pre-genetic testing (pretest) education alternative in clinical practice, to better serve a more diverse patient population at risk for hereditary cancers.

Intraperitoneal Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Cancer of the Peritoneal Cavity

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving paclitaxel albumin-stabilized nanoparticle formulation directly into the abdomen may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal paclitaxel albumin-stabilized nanoparticle formulation in treating patients with advanced cancer of the peritoneal cavity.

Effects of Cytotoxic Chemotherapy and PARP Inhibition on the Genomic Contexture of Ovarian Cancer

EFFECTS OF CYTOTOXIC CHEMOTHERAPY AND PARP INHIBITION ON THE GENOMIC CONTEXTURE OF OVARIAN CANCER: TR\_NACT\_OV/17 In order to approach the above open questions, ultimately aiming in understanding the effects of cancer drugs on tumor biology and hence in selecting the proper drugs for the patients in the context of Precision Medicine, the objective of this study is to study the genomic characteristics of ovarian tumors before and after treatment with classic neoadjuvant chemotherapy (NACT) and with the more recently approved PARP inhibitor olaparib.

Real World Data Analysis of PARP Inhibitors Use in Patients With Ovarian Cancer

Real-world clinical outcomes and toxicity data will be evaluated in patients with advanced high grade ovarian cancer who will receive PARP inhibitors.

Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies

Background: Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is hyperthermic (heated) chemotherapy that washes the inside of the abdomen. CRS with HIPEC may help people with peritoneal carcinomatosis. These are tumors that have spread to the lining of the abdomen from other cancers. Researchers think they can improve the results of CRS with HIPEC treatment on these tumors by choosing the chemotherapy drugs used in HIPEC. Objective: To see if HIPEC after CRS can be improved, using either a model called the SMART (Sustained Microenvironment for Analysis of Resected Tissue) System or using 3-D cell culture (organoid) models, in order to test different chemotherapy drugs on tumors that were surgically removed prior to HIPEC treatment (these models are not attached to the body) versus tumors that were treated with HIPEC while still inside the body before being immediately surgically removed. Eligibility: Adults ages 18 and older who have peritoneal carcinomatosis that cannot be fully removed safely with surgery. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Electrocardiogram (EKG) Computed tomography (CT) scan Other imaging scans, as needed Tumor biopsy, if needed Laparoscopy (small cuts are made in the abdomen, and a tube with a light and a camera is used to see the organs in the abdomen), if needed Participants will enroll in NIH protocol #13C0176. This allows their tumor samples to be used in future research. Some screening tests may be repeated in the study. Participants will have CRS. As many of their visible tumors will be removed as possible during surgery except for a few specific tumors left to receive the HIPEC treatment. Then they will receive HIPEC and the remaining tumors will be immediately removed. Participants will be in the hospital for 7-21 days after this surgery (CRS with HIPEC). Participants will give tumor, fluid samples (from the abdomen during surgery), blood, saliva, cheek swab, and stool for research. They will complete surveys about their health and quality of life. Participants with peritoneal mesothelioma (mesothelioma primary only) will have genetic (DNA) testing to determine clinical (CLIA level) germline BAP1 status for research use. Participants will have follow-up visits for up to 5 years from CRS with HIPEC. If there is disease progression, participants may have CRS with HIPEC again. Participants will then have follow-up visits for up to 5 years from the date of last CRS with HIPEC.

Collection of Blood From Patients With Cancer, Other Tumors, or Tumor Predisposition Syndromes for Genetic Analysis

Background: \- Some genes may be associated with a greater chance of side effects during cancer treatment. These genes may also make certain treatments less effective. Researchers want to collect blood or cheek swab samples from people having cancer treatment to study these genes. Objectives: \- To obtain a blood or cheek swab sample to study genetic differences that may affect cancer treatment. Eligibility: \- Individuals with cancer who are being treated at the National Cancer Institute. Design: * Participants will provide a blood sample for study. * Participants who have blood-based cancer, such as leukemia, will provide a cheek swab sample. * If the blood or cheek swab sample does not have enough genetic material for analysis, an additional sample may be collected.

A Study to Assess Adverse Events, Change in Disease Activity and How Intravenous ABBV-253 Moves Through the Body in Adult Participants With Advanced Solid Tumors

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events, change in disease activity and pharmacokinetics of ABBV-253. ABBV-253 is an investigational drug being developed for the treatment of advanced solid tumors. This open-label study consists of two parts. In Part 1 (ABBV-253 dose escalation), participants with any of the eligible cancer types will receive 1 of 4 (or more) doses of ABBV-253. Each cohort receives a higher dose, lower dose, or the same dose of ABBV-253 than the previous group. In Part 2 (ABBV-253 dose optimization), a new group of participants with NSCLC will be randomly put into pre-determined dose groups to receive 1 of 3 doses of ABBV-253. Approximately 130 participants will be enrolled in the study at approximately 11 sites worldwide. Participants will receive intravenous (IV) infusion of ABBV-253, as part of the 4 year study. There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effects of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

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.

Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers

Background: In a new cancer therapy, researchers take a person s blood, select a certain white blood cell to grow in the lab, and then change the genes of these cells using a virus. The cells are then given back to the person. This is called gene transfer. For this study, researchers will modify the person s white blood cells with anti-CD70. Objectives: To see if a gene transfer with anti-CD70 cells can safely shrink tumors and to be certain the treatment is safe. Eligibility: Adults age 18 and older diagnosed with cancer that has the CD70-expressing cancer. Design: Participants will be screened with medical history, physical exam, scans, and other tests. They may by admitted to the hospital. Leukapheresis will be performed. For this, blood is removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm. Eligible participants will have an intravenous catheter placed in their upper chest. Over several days, they will get chemotherapy drugs and the anti-CD70 cells. They will recover in the hospital. Participants will take an antibiotic for 6 months after treatment. They will repeat leukapheresis. Participants will visit the clinic every 1-3 months for the first year after treatment, every 6 months for the second year, and then as determined by their physician. Follow-up visits will take 1-2 days. At each visit, participants will have lab tests, imaging studies, and a physical exam. Throughout the study, blood will be taken and participants will have many tests to determine the size and extent of their tumor and the treatment s impact.

Safety in Ovarian Cancer for Average-Risk Women - Analysis

This study is designed to evaluate the safety, specificity, and downstream diagnostic burden of the Evident™ Ovarian Cancer Screening Test in average-risk postmenopausal women. Participants will provide a blood sample for screening and will be followed for approximately 12 months to assess test safety, specificity, downstream diagnostic procedures, and ovarian cancer outcomes.

A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors

The purpose of this study is to find out whether the study drug, LY4052031, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors including urothelial cancer. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.

A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

The goal of the Monotherapy Dose Escalation phase (Part 1) of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Monotherapy Expansion phase of the study (Part 2) is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D). The goal of the Combination Dose Escalation phase (Part 3) of the study is to identify the RDE of NKT3964 in combination with chemotherapy in adult subjects with advanced/metastatic endometrial cancer. The goal of the Combination Expansion phase of the study (Part 4) is to evaluate the preliminary anti-tumor activity of NKT3964 in combination with chemotherapy at the RDE based on ORR.

Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression

This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors historically known for expression of EphA2. The main goals of this study are to: * Find the recommended dose(s) of BT5528 that can be given safely to participants alone and in combination with nivolumab * Learn more about the side effects of BT5528 * Learn about how effective BT5528 is for the treatment of ovarian cancer, urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head and neck cancer (HNSCC), and gastric/upper gastrointestinal cancer. * Learn more about BT5528 therapy alone and in combination with nivolumab.

Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer

Background: Many cancer cells produce substances called antigens that are unique to each cancer. These antigens stimulate the body s immune responses. One approach to treating these cancers is to take disease-fighting white blood cells from a person, change those cells so they will target the specific proteins (called antigens) from the cancer cells, and return them to that person s blood. The use of the white blood cells in this manner is one form of gene therapy. A vaccine may help these modified white cells work better. Objective: To test a cancer treatment that uses a person s own modified white blood cells along with a vaccine that targets a specific protein. Eligibility: Adults aged 18 to 72 years with certain solid tumors that have spread after treatment. Design: Participants will undergo leukapheresis: Blood is removed from the body through a tube attached to a needle inserted into a vein. The blood passes through a machine that separates out the white blood cells. The remaining blood is returned to the body through a second needle. Participants will stay in the hospital for 3 or 4 weeks. They will take chemotherapy drugs for 1 week to prepare for the treatment. Then their modified white cells will be infused through a needle in the arm. They will take other drugs to prevent infections after the infusion. The vaccine is injected into a muscle; participants will receive their first dose of the vaccine on the same day as their cell infusion. Participants will have follow-up visits 4, 8, and 12 weeks after the cell infusions. They will receive 2 or 3 additional doses of the boost vaccine during these visits. Follow-up will continue for 5 years, but participants will need to stay in touch with the gene therapy team for 15 years. ...

A Clinical Trial of Raludotatug Deruxtecan (R-DXd) With or Without Bevacizumab in Participants With Ovarian Cancer Who Have Progressed During Treatment With PARP-inhibitors Treatment on First Line Maintenance (MK-5909-008/ENGOT-ov107/GOG-3142 / REJOICE-Ovarian05)

Researchers are looking for new ways to treat advanced, high-grade ovarian cancer (OC). Advanced means the cancer has spread to other parts of the body (metastatic) and may not be removed with surgery. High-grade means the cancer cells grow and spread quickly. This trial includes types of OC that started in cells that cover the ovaries, in the lining of the belly, or in the fallopian tubes. The usual treatment for high-grade OC may include one or both of these: * Chemotherapy, which is a treatment that uses medicine to destroy cancer cells or stop them from growing. * Bevacizumab, which is a targeted therapy that works to control how specific types of cancer cells grow and spread and targets tumor blood vessels. Researchers want to learn about the trial medicine, raludotatug deruxtecan (also called R-DXd or MK-5909), when given with and without bevacizumab and how participants respond to it. R-DXd is an antibody drug conjugate (ADC). An ADC is a type of medicine that attaches to a specific target on cancer cells and delivers treatment to destroy those cells. The goals of this trial are to learn if participants who receive R-DXd, with or without bevacizumab, live longer overall and without their cancer growing or spreading compared to those who receive usual treatment.

Study of CryptiVax-1001 in Maintenance Setting for Advanced Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Ovarian, fallopian tube, or primary peritoneal cancer, collectively referred to as ovarian cancer, remains the deadliest type of gynaecological cancer. The most common and aggressive form is called high-grade serous ovarian cancer. The main purpose of this study is to understand whether an experimental study vaccine, CryptiVax-1001, is safe when administered to patients with high-grade serous ovarian cancer (HGSOC). The study vaccine is a cancer vaccine, which aims to delay or possibly prevent the cancer from coming back. However, as this is the first study of the vaccine in patients, the primary purpose of this study is to assess the safety of the study vaccine. Following surgery and platinum-based chemotherapy participants may enter the trial and receive CryptiVax-1001 as an explorative maintenance therapy. The main purposes of this study are therefore to: * assess how well the study vaccine is tolerated and identify any side effects. * analyse the study vaccine's capacity to activate your immune system The study will test escalating dose levels of CryptiVax-1001 based on the safety evaluations to estimate appropriate future dose levels for CryptiVax-1001.

EHR Intervention to Increase HBOC Genetic Testing

The purpose of this research study is to test how well a new approach - using tools built into the electronic health record (EHR)- can help increase genetic testing for hereditary breast and ovarian cancer (HBOC) in women who have a family history that puts them at higher risk. The study will also look at what helps or gets in the way of using these tools in everyday clinical care. As part of this study, the investigators are also evaluating a website called RealRisks, which is designed to support patients in understanding their risk and making informed decisions about genetic testing. By studying how patients and primary care providers use this tool, the investigators hope to improve the way decision support tools are used to guide conversations and decisions about HBOC testing.

Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression

The purpose of this study is to evaluate INCB123667 versus investigator's choice of chemotherapy in participants with platinum-resistant ovarian cancer with cyclin E1 overexpression.

Risk Reducing Salpingectomy With Delayed Oophorectomy as an Alternative to Risk- Reducing Salpingo-oophorectomy in High Risk-Women to Assess the Safety of Prevention - US Cohort Study

This is a prospective preference study that will evaluate non-inferiority of the innovative treatment (RRS with delayed RRO) as compared to the standard treatment (RRSO) with respect to high grade serous (ovarian) cancer incidence

Long-Term Follow-up Study of Subjects Treated With Autologous T Cells Using the Sleeping Beauty System to Express TCRs

Long-Term Follow-Up Study for Subjects Enrolled in the Phase I/II Study of Autologous T Cells Engineered using the Sleeping Beauty System to Express T cell Receptors (TCRs) Reactive Against Cancer-specific Mutations in Subjects with Solid Tumors

68Ga-SorB PET/CT Imaging in Patients With Solid Tumors

This prospective, single-center, open-label exploratory diagnostic study aims to evaluate the safety, feasibility, and diagnostic performance of the novel Sortilin-targeted PET tracer 68Ga-SorB in patients with solid tumors. Eligible participants with confirmed or suspected melanoma, hepatocellular carcinoma, lung cancer, pancreatic cancer, breast cancer, ovarian cancer, or cholangiocarcinoma will undergo 68Ga-SorB PET/CT imaging. The imaging findings will be compared with standard-of-care 18F-FDG PET/CT, using pathology results and/or clinical follow-up as the reference standard. The primary objectives are to evaluate the safety and tolerability of 68Ga-SorB, assess imaging feasibility, and characterize tumor uptake using quantitative PET parameters, including SUVmax and tumor-to-background ratio (TBR). Secondary exploratory objectives include comparing lesion detection between 68Ga-SorB PET/CT and 18F-FDG PET/CT, assessing diagnostic sensitivity and specificity, evaluating imaging characteristics across different tumor types, and exploring the correlation between Sortilin expression and tracer uptake. This study will provide preliminary clinical evidence supporting the development of Sortilin-targeted molecular imaging and future theranostic applications.