Clinical Research Directory

Study to Assess the Efficacy and Safety of Rina-S With or Without Bevacizumab Compared to Investigator's Choice of Platinum-based Chemotherapy With or Without Bevacizumab as Second-line Treatment in Participants With Recurrent Platinum-sensitive Ovarian Cancer

This Phase 3 study will be conducted in different countries around the world with up to about 688 participants. The purpose of this study is to evaluate how well Rina-S works against ovarian cancer in combination with or without bevacizumab and how it compares to an investigator's choice of platinum-based chemotherapy with or without bevacizumab. Participants will receive either: * Rina-S monotherapy (by itself), * Rina-S plus bevacizumab, * investigator's choice chemotherapy (by itself) (standard of care), or * investigator's choice chemotherapy plus bevacizumab (standard of care). No participants will be given placebo. Participants will participate in 1 of 2 arms. The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open. Participants will be asked to attend 1 to 3 visits at the study clinic for each cycle (duration of cycle is 3 or 4 weeks, depending on medication received). During visits, there will be various tests (such as blood draws) and procedures (such as recording of heart activity and imaging) to monitor whether the study treatment is safe and effective. The overall study duration (including screening, treatment, and follow-up) will be different for every participant.

A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A\*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies

Study of TUB-040 Given With Standard Ovarian Cancer Drugs in Patients With Fast-growing Ovarian Cancer

The goal of this clinical study is to learn more about the safety, tolerability, and preliminary effectiveness of TUB-040 when given in combination with standard ovarian cancer treatments in participants with high-grade epithelial serous or endometrioid ovarian cancer. This study will also evaluate the appropriate dose of TUB-040 when used with carboplatin (Carbo) and bevacizumab (BEV), including determining the maximum tolerated dose (MTD) in participants with platinum-sensitive ovarian cancer.

Phase 3 Study of INCB123667 Plus Bevacizumab Versus Bevacizumab Alone as First-Line Maintenance Therapy in Ovarian Cancer Overexpressing Cyclin E1

The purpose of this study is to evaluate INCB123667 in Combination With Bevacizumab Versus Bevacizumab Alone as First-Line Maintenance Therapy in Participants With Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Overexpressing Cyclin E1.

Tissue Acquisition and Genomics Analysis of Breast Cancer and Other Gynecologic Malignancies

Background: A person s blood, tissue, and other samples contain DNA. Cancer is a disease of cells that are not working properly. It is caused by changes in DNA that build up. Researchers want to do future studies on DNA changes This may help them learn how to guide treatment for cancer. They need biological samples like tumors, blood, and urine for these studies. Objective: To create a place to collect and store biological samples from people with gynecologic malignancies like breast cancer. Samples from certain relatives of theirs will be collected too. Eligibility: Adults ages 18 and older who are being seen at NIH for breast cancer or other gynecologic malignancy Their biological relatives of the same age Design: Participants will answer questions about their family history. Participants will have a physical exam and medical history. This will include questions about age, ethnicity, and disease history. They will also answer questions about their medical treatments and responses. Participants will give blood and urine samples. Participants may give a tumor tissue sample. This will not be taken specifically for this study. It will be from a previous procedure or one that is already planned. Other samples may be taken only if a procedure is required for treatment. These include bone marrow, cerebrospinal fluid, and other fluids. A group of doctors and other professionals will oversee the sample storage place. The group will review all requests to be sure the use of the specimens is valid. ...

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 of Raludotatug Deruxtecan With or Without Bevacizumab as First-Line Maintenance Treatment in Non-HRD-Positive Advanced Ovarian Cancer (MK-5909-006, (ENGOT-ov102/GOG-3141/ REJOICE-Ovarian 04)

Researchers are looking for new ways to treat ovarian cancer (OC). Current treatment for OC may start with surgery to remove as much of the cancer as possible. After surgery, people may receive chemotherapy. After chemotherapy, standard care options may include: Maintenance treatment, which is used after another therapy to keep the cancer from growing, spreading, or coming back. Bevacizumab is a targeted therapy used as standard maintenance treatment. Targeted therapy works to control how specific types of cancer cells grow and spread. Observation, which is watching to see if cancer grows or worsens. The study medicine, raludotatug deruxtecan- R-DXd, is a targeted therapy. The goal of this study is to learn if people who receive R-DXd maintenance treatment with or without bevacizumab live longer without the cancer getting worse than people who receive standard care.

A Clinical Study of SYS6041 Combination Therapy for Recurrent Ovarian Cancer

This is an open-label, multicenter Phase II clinical study conducted in subjects with recurrent ovarian cancer.

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

The primary purpose of this study is to assess the safety and tolerability of AB598 in participants with advanced malignancies.

Evaluation of the Distribution of 64Cu/68Ga Labeled CM500 in Healthy Volunteers and Patients With Cancer

The objective of this study is to assess two novel positron emission tomography (PET) radiotracers, \[64Cu\]CM500 and \[68Ga\]CM500, for Positron Emission Tomography-Magnetic Resonance Imaging (PET-MR) and Positron Emission Tomography / Computed Tomography (PET-CT) imaging of solid tumors. These tracers have the potential to detect solid tumors throughout the body and may enable doctors to identify smaller tumors than conventional imaging techniques.

Irreversible Electroporation (IRE) for Treating Recurrent Pelvic Tumors (PELFIRE Study)

The goal of this single-center observational cohort study, based on a registry combining retrospectively and prospectively collected data, is to investigate the short- and long-term effects of irreversible electroporation (IRE) in men and women over the age of 18 who receive IRE for recurrence of pelvic tumors not suitable for other local treatment options such as surgery, thermal ablation, and radiotherapy. The main question it aims to answer is whether IRE is safe in this population, and secondarily, whether it is effective in controlling local tumor recurrence.

A Clinical Trial of Sac-TMT in People With Non-HRD Positive Advanced Ovarian Cancer (MK-2870-021)

Researchers are looking for new ways to treat ovarian cancer (OC). Current treatment for OC may start with surgery to remove as much of the cancer as possible. After surgery, people may receive chemotherapy. After chemotherapy, standard care options may include: * Maintenance treatment, which is used after another therapy to keep the cancer from growing, spreading, or coming back. Bevacizumab is a targeted therapy used as standard maintenance treatment. Targeted therapy works to control how specific types of cancer cells grow and spread. * Observation, which is watching to see if cancer grows or worsens The study medicine, sacituzumab tirumotecan (also called sac-TMT), is a targeted therapy. The goal of this study is to learn if people who receive sac-TMT maintenance treatment with or without bevacizumab live longer without the cancer getting worse than people who receive standard care.

A Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Maintenance Treatment Versus Standard of Care in Participants With Platinum-sensitive Recurrent Ovarian Cancer (MK-2870-022/TroFuse-022/ENGOT-ov84/GOG-3103)

The main goals of this study are to learn about the safety of sacituzumab tirumotecan with bevacizumab and if people tolerate it; and if people who take sacituzumab tirumotecan with or without bevacizumab live longer without the cancer getting worse than those who receive standard of care treatment.

Cognitive Impact of Neoadjuvant Chemotherapy for Gynecologic Cancers

The purpose of this research is to assess several components of cognition in patients recently diagnosed with advanced epithelial ovarian cancer and who will be undergoing neoadjuvant chemotherapy for treatment of the cancer. 18 participants will be enrolled and can expect to be on study for approximately 10 months.

Safety, PK and Efficacy of QXL138AM in Patients With Solid Tumors and Multiple Myeloma

Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with locally advanced un-resectable and/or metastatic solid tumors and multiple myeloma. The study is an open-label, multicenter, first in human study to be conducted in two major parts which are further organized into two sub-parts. Part A Dose Escalation is a modified 3+3 with the first two cohorts consisting of one subject each based on the low clinical starting dose. Dose escalation in solid tumors (Part A1) will be followed by dose finding in multiple myeloma (Part A2). Part B consists of dose expansion in solid tumors (Part B1) and multiple myeloma (Part B2) using the recommended dose for expansion from Part A

A Study of Intra-operative Imaging in Women With Ovarian Cancer

The purpose of this study is to find out whether using the PINPOINT imaging system intra-operatively can reduce the risk of anastomotic leaks and other complications after surgery for ovarian cancer, compared with standard intra-operative assessments alone. The PINPOINT endoscopic fluorescence imaging system uses a special camera and a fluorescent (glowing) dye that can evaluate the blood flow of the bowel in real-time. If there is an area that appears concerning, the surgeon can correct the problem during the procedure.

89Zr-DFO-Mirvetuximab PET/CT Imaging for Companion Diagnosis and Response Evaluation in Ovarian Cancer

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in women, with approximately 320,000 new cases and 200,000 deaths annually worldwide, and its incidence is rising. Current treatment mainly relies on surgery, chemotherapy, and radiotherapy, but EOC frequently develops platinum resistance and recurrence. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), was approved by the FDA in 2024 for FRα-positive, platinum-resistant EOC. However, it carries significant toxicities (ocular, interstitial lung disease, peripheral neuropathy) and a modest objective response rate of 33%, with rapid acquired resistance, underscoring the need for patient selection and response prediction via targeted imaging. FRα, a GPI-anchored cell-surface glycoprotein encoded by FOLR1, is minimally expressed in normal adult tissues but overexpressed in various epithelial tumors, including ovarian cancer. Its overexpression promotes invasion, metastasis, and potentially drug resistance, making it a promising theranostic target. While ¹⁸F-FDG PET/CT is widely used, it has limitations in detecting low-activity or small lesions and shows suboptimal sensitivity/specificity for nodal metastases. Radiolabeled folate probes (e.g., ⁹⁹ᵐTc-EC20) have demonstrated excellent FRα-targeting and clinical utility in selecting patients for FRα-directed therapies. Our team has developed ⁸⁹Zr-DFO-Mirvetuximab by conjugating the anti-FRα monoclonal antibody with the chelator p-isothiocyanatobenzyl-desferrioxamine B and radiolabeling with ⁸⁹Zr. Preclinically, this probe exhibited favorable stability, safety, and specific targeting of FRα-high tumors in xenograft models. Building on these results, we plan a clinical study enrolling 20 patients with newly diagnosed stage IV or first-recurrent EOC, who will undergo both ⁸⁹Zr-DFO-Mirvetuximab PET/CT and ¹⁸F-FDG PET/CT. The study aims to correlate radiotracer uptake with FRα expression and to demonstrate the superior performance of ⁸⁹Zr-DFO-Mirvetuximab in identifying and delineating ovarian cancer lesions compared to ¹⁸F-FDG

Clinician Nudge to Referral of Adnexal Masses to Gynecologic Oncology

The goal of this study is to test the effectiveness of clinician nudges on referrals to gynecologic oncology in patients with suspected ovarian cancer. The primary outcome will be whether or not patients were referred to gynecologic oncology within 14 days of their abnormal imaging results. Secondary and exploratory outcomes are whether the gynecologic visit occurred within 60 days of abnormal imaging and the time from abnormal imaging results to gynecologic oncology visit.

A Study Evaluating the Integrative Medicine at Home (IM@HOME) Program in People With Cancer

The overarching long-term goal of the Integrative Medicine for Patient-reported Outcomes Values and Experience (IMPROVE) research program is to evaluate whether integrating a virtual mind-body programming, Integrative Medicine at Home (IM@Home), will improve patient perceived values, outcomes, and experiences as they undergo systemic cancer treatment such as chemotherapy, immunotherapy, radiotherapy, targeted agents, cytoreductive surgery.

Phase 1, Safety and Tolerability Study of XmAb541 in Advanced Solid Tumors

The primary purpose of this study is to determine whether the investigational drug XmAb541 is safe and well tolerated, and to determine an optimal and safe dose(s) for further study. The study will also evaluate the effect of XmAb541 on tumor outcomes.

Nirogacestat in Ovarian Granulosa Cell Tumors

This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.

DESTINY-PANTUMOUR04

This study will evaluate the effectiveness of T-DXd in patients with HER2-positive (IHC 3+) locally advanced, unresectable, or metastatic solid tumors who have received prior systemic treatment for metastatic or advanced disease and have no satisfactory alternative treatment options in a real-world setting in the US

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.

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.