NCT04895709Phase 1, Phase 2Recruiting
Bristol-Myers Squibb · Community Cancer Institute, Clovis, California
The purpose of this study is to assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab, docetaxel, or Pumitamig in participants with advanced solid tumors. This study is a first-in-human (FIH) study of BMS-986340 in participants with advanced solid tumors.
Eligibility: 18 Years to · All · Inclusion Criteria
* Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable.
* Eastern Cooperative Oncology Group Performance Status of 0 or 1.
* Radiographically documented progressive disease on or after the most recent therapy.
* Received standard-of-care therapies, (except for Part 1C, 2C and 2D, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated.
* Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant.
Exclusion Criteria
* Women who are pregnant or breastfeeding.
* Primary central nervous system (CNS) malignancy.
* Untreated CNS metastases.
* Leptomeningeal metastases.
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment.
* Active, known, or suspected autoimmune disease.
* Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment.
* Prior organ or tissue allograft.
* Uncontrolled or significant cardiovascular disease.
* Major surgery within 4 weeks of study drug administration.
* History of or with active interstitial lung disease or pulmonary fibrosis.
* Other protocol-defined inclusion/exclusion criteria apply.
NCT05269381Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
Eligibility: 16 Years to · All · Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.
PHASE I PRE-REGISTRATION, ALL:
* Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests
* NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
* NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
* Provide written informed consent. For pediatric patients (age 16-17 years):
* Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations.
* Willing to return to enrolling institution for follow-up
* Willing to provide blood specimens for research
* Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.
* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
* Anticipated life expectancy \> 6 months
* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).
* The following lab values obtained ≤ 28 days prior to pre-registration:
* Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion)
* Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L
* Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases
* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula
* International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy
PHASE I REGISTRATION, ALL:
* Successful sequencing and production of REAL-Neo vaccine
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* ECOG PS 0 or 1
* Anticipated life expectancy \> 6 months
* The following lab values obtained ≤ 14 days prior to registration:
* Hemoglobin ≥ 9.0 g/dl
* ANC ≥ 1500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1.5 x ULN
* ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)
* PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy
* Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula
* Provide written informed consent
* Willing to provide blood and tissue sp
NCT06956144Phase IIRecruiting
The First Affiliated Hospital of Xiamen University · The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361000, Xiamen
To evaluate the efficacy of targeted CAIX-specific probe PET imaging in the diagnosis and staging of kidney cancer, as well as to assess its role in prognosis prediction and treatment evaluation for kidney cancer.
Eligibility: 18 Years to 74 Years · All · 1. Voluntary participation with the patient or their legal representative able to sign the informed consent form.
2. Adult patients (age between 18 and 75 years), regardless of gender.
3. Patients with clinically suspected or confirmed primary kidney cancer (supporting evidence includes imaging data and histopathological examination; specific case types include clear cell carcinoma, papillary renal cell carcinoma, and chromophobe renal cell carcinoma) who agree to undergo histopathological examination (if not already performed prior to imaging).
4. Patients must have undergone enhanced CT, with the enhanced CT examination conducted within 2 weeks prior to enrollment.
5. ECOG performance status score of 0-3.
6. Laboratory parameters must meet the following criteria:
1. ALT and AST must not exceed 3 times the upper limit of normal; BUN and creatinine must not exceed 1.5 times the upper limit of normal.
2. Hematological parameters: 2 x 10\^9/L ≤ WBC ≤ 2 x 10\^10/L, PLT ≥ 80 x 10\^9/L, Hb ≥ 80 g/L.
7. Willing and able to comply with follow-up visits, treatment plans, and related laboratory examinations.
NCT07590310EARLY_Phase 1Recruiting
Peking University Cancer Hospital & Institute · Peking University Cancer Hospital, Beijing, Haidian
According to the 2020 global cancer statistics, renal carcinoma ranks as the fourteenth most common malignant tumor worldwide. In 2020, there were 431,288 new cases and 179,368 deaths from renal cancer, and both the incidence and mortality rates are projected to continue rising by 2025. Early non-invasive diagnosis of clear cell renal cell carcinoma (ccRCC) is crucial for improving prognosis. Nuclear medicine molecular imaging offers the advantages of real-time, dynamic, and non-invasive detection of lesions throughout the body. However, there is currently a lack of highly efficient and targeted molecular probes for early and accurate diagnosis of this tumor in clinical practice.
The high expression of CAIX plays a central role in the pathogenesis of renal cancer by altering cellular metabolism, inducing angiogenesis, promoting epithelial-mesenchymal transition (EMT), invasion, and metastatic spread. CAIX is highly expressed in 95% of ccRCC cases. In fact, CAIX expression levels have been reported as an independent predictor of survival in advanced ccRCC. Moreover, CAIX expression in normal tissues is limited, primarily restricted to the stomach, the basolateral aspects of proliferating small intestinal crypt epithelial cells, and the gallbladder. Therefore, the differential expression of CAIX between ccRCC tumors and normal tissues highlights its potential as a robust target for nuclear medicine molecular probe research and development in ccRCC.
This study utilized high-throughput screening to identify small molecules with high affinity for CAIX. These molecules were subsequently cyclized and modified to enhance their in vivo stability. A bifunctional chelator, H3RESCA, was introduced at the C-terminus to construct the small-molecule compound RESCA-CAIX-LT. PET probes were prepared by radiolabeling with 68Ga or 18F, and their diagnostic efficacy for renal cancer was investigated. Small-animal PET imaging initially demonstrated that the probe exhibits high affinity and excellent imaging performance. The modifications also altered the in vivo metabolic profile of the original design, reducing non-specific uptake in organs such as the stomach, small intestine, and gallbladder. Furthermore, toxicological experiments confirmed the probe's high safety profile and in vivo stability.
Eligibility: 18 Years to 75 Years · All · -Hematological, hepatic, and renal functions meeting the following criteria: Complete Blood Count: WBC ≥4.0×10⁹/L or Neutrophils ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥90 g/L; Coagulation: PT or APTT ≤1.5 × ULN (Upper Limit of Normal); Hepatic Function: T-Bil ≤1.5 × ULN; ALT/AST ≤2.5 × ULN (or ≤5 × ULN for subjects with liver metastases); ALP ≤2.5 × ULN (or ≤4.5 × ULN for subjects with bone or liver metastases); Renal Function: BUN ≤1.5 × ULN, SCr ≤1.5 × ULN.
Normal cardiac function;
* Expected survival ≥12 weeks;
* Good compliance with follow-up;
* At least one measurable target lesion according to RECIST 1.1 criteria;
* Women of childbearing potential (aged 18-49) must have a negative pregnancy test within 7 days prior to the examination. Male and female patients of childbearing potential must agree to use effective contraception to prevent pregnancy during the study and for 3 months after the examination;
* Patients for whom the clinician recommends a PET/CT examination for tumor diagnosis and staging;
* Patients are fully capable of understanding the study, voluntarily agree to participate, and provide written informed consent.
NCT07561957NARecruiting
St. James's Hospital, Ireland · St. James's Hospital, Dublin
The goal of this study is to establish whether use of a digital intervention can improve adherence and alignment with the Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease (CKD) 2024 Guidelines.
A subset of the study will focus on whether the intervention improves outcomes for young adults living with CKD, in the context of the imminent co-location of Children's Health Ireland on the St. James's Hospital campus.
Young adults with CKD transitioning to adult services are recognised as a high-risk and vulnerable cohort, with many individuals unaware of increased cardiovascular risk and mortality¹². In response, and in the context of the co-location of Children's Health Ireland on the St. James's Hospital site, a young adult nephrology clinic has been established.
The KDIGO CKD 2024 Guidelines identify transition as a period of increased risk and include recommendations regarding cardiovascular risk factor targets and the use of therapies known to delay CKD progression³.
Electronic communication is a preferred method for accessing health information among many young adults⁴⁵ and aligns with Sláintecare digital health strategies⁶. A recently established, award-winning St. James's Hospital renal smartphone application is currently used by over 3,000 individuals living with CKD.
The study aims to determine whether use of the application improves adherence to KDIGO guideline recommendations, with the objective of delaying CKD progression and associated complications. The application will support optimisation of care by signposting opportunities for evidence-based interventions (e.g., SGLT2 inhibitors, renin-angiotensin system inhibition) to healthcare providers. The application will also provide participants with tailored recommendations, reminders, educational materials, and collection of patient-reported outcome measures.
Due to the diverse population and range of specialties at St. James's Hospital, the young adult clinic serves distinct subgroups, including individuals with sickle cell anaemia and survivors of cancer and haematological malignancies. These populations will be examined in the context of KDIGO guideline implementation, contributing to a limited international evidence base.
This research evaluates an intervention designed to improve care for adults living with chronic kidney disease.
Eligibility: 16 Years to 30 Years · All · * Adults aged ≥16 years.
* Diagnosed with CKD stages 1-5.
* Owns a smartphone and is capable of using mobile applications.
* Provides informed consent.
NCT06536439NARecruiting
University Hospital, Ghent · AZORG, Aalst
A proposed new tool ('DIPLANN-tool' - Digital Planning in Nephrectomy) for predicting kidney perfusion zones on a segmented 3D model during robot-assisted partial nephrectomy (RAPN) for localized renal cancer demonstrated high accuracy when planning selective clamping (SC) for RAPN. However, the tool's clinical added value still needs to be confirmed. Therefore, a randomized controlled trial using a study and control group is the preferred study design.
Experimental group: the use of the DIPLANN-tool + conventional computed tomography (CT) imaging for preoperative planning and perioperative guidance during RAPN.
Control group: the use of only conventional CT imaging for preoperative planning and perioperative guidance during RAPN (= current standard of care).
The primary endpoint is planning and performing as planned a SC strategy. Secondary endpoints include patients' health, patients' insight and surgeons' benefits.
Eligibility: 18 Years to · All · * aged 18 years or above
* cT1-2 N0 M0 renal mass
* planned to undergo RAPN
* multiphase CT scan with arterial phase available
* voluntary given and written informed consent
* sufficient in at least one of the study languages: Dutch, English, French
For the primary objective, SC needs to be deemed possible either according to the DIPLANN-tool in combination with conventional CT imaging or according to conventional CT imaging only, as assessed by an independent surgeon (between inclusion and randomization) who will not be involved in the RAPN surgical procedure, in order to be included in the analysis set. On the DIPLANN tool, SC is deemed feasible if \>= 90% tumor ischemia and \<= 70% renal parenchyma ischemia can be achieved. If these criteria are met, but it is technically or anatomically not feasible according to the independent surgeon to perform SC, he can deviate from these criteria and thus claim SC is not deemed possible. The results for the total population (patients in which SC is deemed possible AND impossible pre-operatively by an independent surgeon) will also be analyzed as a secondary objective.
