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.
NCT07462507Phase 2Recruiting
Washington University School of Medicine · Washington University School of Medicine, St Louis, Missouri
Adult patients with primary or secondary central nervous system malignancies will be invited to undergo a baseline \[C-11\]-CS1P1 PET scan and a follow-up scan within 24 months of the baseline scan (preferably within 6-months post-treatment).The study will describe patterns of tracer uptake in tumors and normal brain and explore how these patterns relate to MRI findings, treatments received, and clinical outcomes.
Eligibility: 18 Years to · All · * Male or female, any race
* Age ≥ 18 years
* Capable of providing written informed consent OR having a legally authorized representative (LAR) to provide informed consent for volunteering to undergo research procedure
* Has a clinical, radiographic, or pathological diagnosis of primary or secondary CNS malignancy that has not been treated with radiotherapy
NCT07505173Phase 2Recruiting
Tianjin Medical University Cancer Institute and Hospital · Tianjin Medical University Cancer Institute and Hospital, Tianjin
This is a single-arm, multicenter, open-label, phase Ⅱ exploratory clinical study, which plans to enroll 74 treatment-naive patients with EGFR-sensitive mutations (exon 19 deletion, exon 21 L858R mutation) and symptomatic brain metastases from non-small cell lung cancer (NSCLC). The primary objective is to evaluate the intracranial progression-free survival (iPFS) of hippocampal-sparing whole-brain radiotherapy (PTV: 20Gy/10 fractions) combined with simultaneous integrated boost to brain metastases (PGTV: 40Gy/10 fractions) plus osimertinib (80mg orally once daily). The secondary objectives are to assess efficacy indicators including overall progression-free survival (PFS), intracranial/systemic objective response rate (ORR), as well as safety. The primary endpoint is iPFS, supplemented by secondary endpoints such as PFS, ORR, disease control rate (DCR), overall survival (OS), adverse events (AE) evaluated per NCI-CTCAE v5.0 criteria, and neurocognitive function scores (MMSE/HVLT-R). By optimizing the combined mode of radiotherapy and targeted therapy, this study aims to provide a safer and more effective treatment option for such patients, balancing tumor control and quality of life protection.
Eligibility: 18 Years to 75 Years · All · * Signed a written informed consent form prior to enrollment;
* Aged 18-75 years;
* Histopathologically confirmed non-small cell lung adenocarcinoma (NSCLC); EGFR gene test confirmed EGFR sensitive mutations, including exon 19 deletion (19del) and exon 21 L858R mutation (verified and confirmed by investigators at the respective study centers);
* Brain metastasis confirmed by contrast-enhanced cranial CT/MRI; the number of brain metastatic lesions requiring local dose escalation is 1-10, with at least one measurable intracranial lesion having a diameter ≥10 mm; the distance between metastatic lesions and important cerebral functional areas meets radiotherapy-related requirements; at least one measurable lesion (per RECIST v1.1 criteria) confirmed by contrast-enhanced extracranial CT/PET-CT;
* Symptomatic brain metastasis;
* ECOG performance status score: 0-2;
* Expected survival time of no less than 12 weeks;
* No prior anti-tumor treatment received for NSCLC;
* Normal function of vital organs, meeting the following requirements (no blood components or cell growth factors administered within 14 days):
A) Routine blood test criteria: Hb ≥100 g/L; ANC ≥1.5×10⁹/L; PLT ≥75×10⁹/L; B) Biochemical test criteria: TBIL ≤1.5×ULN (upper limit of normal); ALT and AST ≤2.5×ULN (for patients with liver metastasis, ALT and AST ≤5×ULN); serum creatinine ≤1.5×ULN, creatinine clearance rate ≥50 ml/min (calculated based on the Cockroft-Gault formula); C) Coagulation function criteria: INR ≤1.5×ULN and APTT ≤1.5×ULN; D) Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥50%;
\- For non-surgically sterilized patients or women of childbearing potential: a medically approved contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) must be used during the study treatment period and for 3 months after the end of study treatment; non-surgically sterilized women of childbearing potential must have a negative serum or urine HCG test within 7 days prior to study enrollment, and must not be breastfeeding.
All subjects voluntarily participate in the study, with good compliance and willingness to cooperate with safety and overall survival follow-up.
NCT07688356Phase 2Recruiting
Samsung Medical Center · Samsung Medical Center, Seoul
This is a Phase 2, open-label, single-arm clinical study designed to evaluate the efficacy and safety of Belvarafenib in patients with BRAF-altered primary brain tumors (Cohort 1) and metastatic brain tumors (Cohort 2). Eligible patients are those with a confirmed BRAF alteration identified by next-generation sequencing (NGS).
Patients who meet the eligibility criteria will receive a detailed explanation of the study, including its purpose, procedures, potential benefits, and risks. Only patients who voluntarily provide written informed consent will be enrolled.
All enrolled patients will receive Belvarafenib monotherapy at a dose of 450 mg twice daily (BID). The study drug will be taken orally within 30 minutes after meals with at least 200 mL of water, preferably at approximately 12-hour intervals each day. One treatment cycle is defined as 28 consecutive days of continuous dosing without a planned treatment break. Patients will receive treatment for six cycles (approximately six months) as the initial treatment period. Treatment may be extended or discontinued earlier at the investigator's discretion based on clinical benefit, disease status, and tolerability.
During the study, patients will undergo regular clinical evaluations, including physical examinations, vital sign assessments, laboratory tests, and monitoring for adverse events. Radiologic assessments using MRI and/or CT will be performed at scheduled intervals to evaluate tumor response and disease progression. The study aims to determine whether Belvarafenib can control tumor growth, delay disease progression, and improve clinical outcomes in patients with BRAF-altered brain tumors.
If treatment-related toxicities occur, dose reductions are permitted according to the protocol. The dose may be reduced from 450 mg BID to 300 mg BID, and subsequently to 200 mg BID, if clinically indicated. Temporary treatment interruption may also be implemented until toxicity resolves. If unacceptable toxicity persists despite dose modification, treatment will be permanently discontinued.
Study treatment may be discontinued if any of the following occurs: confirmed disease progression, unacceptable toxicity, withdrawal of informed consent, inability to comply with the study protocol, receipt of other anticancer therapies that may interfere with study outcomes, or if the investigator determines that continued treatment is no longer in the patient's best interest. However, if radiologic disease progression is observed but the investigator determines that the patient continues to derive clinical benefit, treatment beyond progression may be considered after discussion with the sponsor, with appropriate documentation of the rationale.
After discontinuation of study treatment, patients will receive the most appropriate subsequent management, including best supportive care (BSC) or other anticancer therapies, as determined by the treating investigator. Follow-up assessments will continue according to the study protocol.
The primary objective of this study is to evaluate the efficacy of Belvarafenib in patients with BRAF-altered primary and metastatic brain tumors, while also assessing its safety profile. The results of this study are expected to provide important clinical evidence supporting the development of new treatment strategies for patients with BRAF-altered brain tumors.
Eligibility: 19 Years to · All · (Applicable to Both Cohorts)
1. Male or female patients aged 19 years or older.
2. Histologically confirmed primary brain tumor or metastatic brain tumor.
3. Documented BRAF mutation, including point mutations (e.g., V600E) or BRAF fusion mutations.
4. Willing and able to provide written informed consent prior to participation in the study.
5. Estimated life expectancy of at least 3 months.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
7. Adequate organ function demonstrated by laboratory assessments performed within 14 days prior to the first dose of study treatment, meeting all of the following criteria:
* Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
* Hemoglobin ≥ 9 g/dL
* Platelet count ≥ 100 × 10⁹/L
* PT/INR and aPTT ≤ 1.5 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with Gilbert syndrome)
* AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN in patients with liver metastases)
* Alkaline phosphatase ≤ 2.5 × ULN (≤ 5 × ULN in patients with liver or bone metastases)
* Albumin ≥ 2.5 g/dL
* Amylase ≤ 1.5 × ULN
* Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance (CrCl) \> 50 mL/min using the Cockcroft-Gault formula
8. Women of childbearing potential (defined as women from menarche until 1 year after menopause unless permanently sterile) and men with partners of childbearing potential must agree to use highly effective contraception throughout the study and for 3 months after the last dose of Belvarafenib.
Women of childbearing potential must have a negative pregnancy test during screening unless surgically sterile.
Acceptable contraceptive methods include:
* Hormonal contraception
* Intrauterine device (IUD) or intrauterine system (IUS)
* Vasectomy or bilateral tubal occlusion
* Complete abstinence Barrier methods (e.g., male or female condoms); if barrier methods are used alone, the use of two complementary barrier methods is recommended.
9. Additional Inclusion Criteria for Cohort 1 (Primary Brain Tumors) 1) Patients with BRAF-mutant primary brain tumors who meet at least one of the following conditions:
\- No available or appropriate local treatment options (e.g., surgery or radiotherapy);
* Radiographic evidence of disease recurrence or progression following standard therapy (including surgery and/or chemoradiotherapy \[CCRT\]), with no further suitable standard treatment available;
* Standard treatment is considered inappropriate or unavailable in the investigator's judgment.
10. Additional Inclusion Criteria for Cohort 2 (Metastatic Brain Tumors)
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1. Patients with brain metastases from BRAF-mutant solid tumors.
2. Patients with radiographic evidence of disease progression after receiving the standard treatment for the primary malignancy, or whose disease is refractory to conventional therapy, regardless of prior exposure to BRAF-targeted therapy, and who have no available or appropriate local treatment options (e.g., surgery or radiotherapy).
3. At least one measurable intracranial lesion, with a maximum of five target lesions, as defined by the Response Assessment in Neuro-Oncology (RANO) criteria.
NCT05649306Phase IIRecruiting
Johns Hopkins University · Sibley Memorial Hospital, Washington D.C., District of Columbia
This research is being done to learn more about coping and survivorship of women with bladder cancer, specifically regarding psychosocial distress and sexual dysfunction. This study is a non-therapeutic study and will randomize participants to a standard of care group and education group. Patients in both groups will be asked to complete surveys regarding their mood and sexual function. Patients in the intervention group will be asked to complete attendance diaries regarding educational and support services utilized. Participants' clinical data will also be collected.
Eligibility: 18 Years to · Female · * Females with bladder cancer
* Willing to answer surveys regarding their psychosocial health and sexual health
NCT07036731NARecruiting
The First Affiliated Hospital with Nanjing Medical University · The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, Nanjing, Jiangsu
This study is a prospective, randomized, multicenter clinical trial aiming to enroll 428 patients with non-muscle-invasive bladder cancer (NMIBC) from the Department of Urology at Jiangsu Provincial People's Hospital and its affiliated centers, who have undergone their initial transurethral resection and are scheduled for a second resection. Within 1-6 weeks after the first resection and prior to the second resection, 100ml of routine urine will be collected and sent within 24 hours to Beijing Genetron Health Clinical Laboratory Co., Ltd. for the extraction of urinary sediment DNA, which will then undergo genome-wide low-depth sequencing. Patients with positive test results will proceed with the second resection, while those with negative results will be randomly assigned in a 1:2 ratio to either the intervention group, which will not undergo a second resection, or the control group, which will undergo the second resection. All enrolled patients will be followed up for two years. The study will statistically analyze and compare the two-year recurrence-free survival rates between the two groups and evaluate the predictive capability of the test results for follow-up recurrence.
Eligibility: 18 Years to 80 Years · All · * Patients with NMIBC who have completed the initial transurethral resection and are scheduled for a second resection, as recommended by guidelines or physician's choice:
1. Incomplete initial TURBT due to various reasons (including large tumor size, high risk of intraoperative bleeding, extensive tumor range, etc.), posing a risk of residual tumor;
2. Absence of muscle layer tissue in the initial resection specimen;
3. Post-initial resection pathology indicating T1 stage;
4. Post-initial resection pathology indicating G3/high-grade tumor, excluding pure carcinoma in situ;
* Ability to provide a 100ml routine urine sample within 1-6 weeks after the initial resection and before the second resection;
* Age ≥ 18 years;
* Willingness to provide basic clinical information, pathology, and subsequent - recurrence monitoring results;
* Willingness to sign the informed consent form.
NCT07475403Phase 2Recruiting
Tianjin Medical University Second Hospital · The Second Hospital of Tianjin Medical University, Tianjin
This study evaluates whether urinary tumor DNA (utDNA) testing, together with clinical, pathologic, and radiographic assessment, can help guide treatment discontinuation and active surveillance in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) treated with bladder-sparing systemic immunotherapy.
Participants receive systemic immune checkpoint inhibitor-based therapy every 3 weeks for an initial 3 cycles. Initial response assessment is performed using transurethral resection of bladder tumor (TURBT) and chest and abdominopelvic computed tomography (CT). Participants without progression to muscle-invasive, regional nodal, or distant metastatic disease then undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy.
After the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, utDNA testing, and chest and abdominopelvic CT. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing, and without radiographic evidence of nodal or distant metastatic disease, discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up according to institutional practice.
The study aims to determine whether a shortened duration of systemic immunotherapy guided by integrated molecular, clinical, pathologic, and radiographic response assessment can maintain favorable oncologic outcomes while reducing unnecessary treatment exposure in this high-risk population.
Eligibility: 18 Years to · All · 1. Age ≥18 years.
2. Histologically confirmed non-muscle-invasive urothelial carcinoma of the bladder classified as very-high-risk (VHR) according to EAU 2025 guideline criteria.
3. Disease considered unresectable by the investigator and multidisciplinary team, defined as complete tumor eradication by standard transurethral resection of bladder tumor (TURBT) being not feasible or unlikely to achieve adequate local control.
4. Patients who are ineligible or refuse for radical cystectomy, after discussion with the treating team.
5. At least one measurable or evaluable bladder lesion/documented residual disease suitable for response assessment by cystoscopy, TURBT/biopsy, pathology, urine cytology, and urinary tumor DNA (utDNA) testing.
6. ECOG performance status 0-2.
7. Adequate organ function, including:
Hematologic function: Absolute neutrophil count ≥1.5 × 10⁹/L, Platelet count ≥100 × 10⁹/L, Hemoglobin ≥9 g/dL Hepatic function: Total bilirubin ≤1.5 × ULN, AST ≤2.5 × ULN, ALT ≤2.5 × ULN Renal function: Serum creatinine ≤1.5 × ULN or Creatinine clearance ≥60 mL/min.
8. Ability to provide urine samples for utDNA testing and urine cytology during treatment and follow-up.
NCT07307456Phase 2Recruiting
Changhai Hospital · ChangHai Hospital, Shanghai, Shanghai Municipality
This is a single-center, prospective, open-label, non-randomized clinical study initiated and conducted by the Department of Urology, Shanghai Changhai Hospital. The Principal Investigators are Professor Zhang Zhensheng and Professor Chen Guanghua. The projected study period is from December 2025 to December 2028. This study aims to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) combined with Bacillus Calmette-Guérin (BCG) intravesical instillation as adjuvant therapy following transurethral resection of bladder tumor (TURBT) in patients with high-risk/very high-risk non-muscle-invasive bladder cancer (NMIBC).
Bladder cancer is a common malignancy of the urinary system, with NMIBC accounting for approximately 75% of initial diagnoses. For high-risk patients who are unresponsive to or experience recurrence after BCG therapy, radical cystectomy remains the standard treatment. However, this procedure is associated with high rates of complications, mortality risk, and significantly negative impacts on quality of life. Therefore, exploring novel combination strategies that effectively reduce recurrence while preserving the bladder is of great clinical importance. This study is based on the successful application of immune checkpoint inhibitors in advanced urothelial carcinoma and recent Phase III trials (e.g., the CREST study) demonstrating the efficacy and safety of combining PD-1/PD-L1 inhibitors with BCG in treatment-naïve high-risk NMIBC. It seeks to investigate the potential of the domestic PD-1 inhibitor toripalimab in combination with standard BCG instillation.
The study plans to enroll 31 patients with histologically confirmed high-risk/very high-risk NMIBC who have not previously received immune checkpoint inhibitors or BCG therapy. All enrolled patients will first receive a single instillation of gemcitabine (2000mg), followed by the combination therapy phase: toripalimab (240mg, intravenous infusion, every 3 weeks for 8 cycles) combined with BCG intravesical instillation (induction phase for 6 weeks, maintenance phases at months 3 and 6). The primary efficacy endpoint is the pathological complete response (CR) rate at approximately 6 months after treatment initiation. Secondary efficacy endpoints include duration of CR, 6-month and 2-year event-free survival (EFS) rates, 1-year and 2-year cancer-specific survival (CSS) rates, time to radical cystectomy, and overall survival (OS). Safety endpoints encompass the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
Statistical analyses will be based on the Full Analysis Set (FAS) and Per-Protocol Set (PPS). The sample size calculation for the primary endpoint (6-month CR rate) is based on historical data assumptions, employing a one-sided test. Safety analyses will include all patients who received at least one dose of study treatment. This study will strictly adhere to the principles of the Declaration of Helsinki, Chinese Good Clinical Practice (GCP) guidelines, and relevant regulations. The study protocol has been submitted for review and approval by the Institutional Review Board (IRB)/Ethics Committee. Written informed consent will be obtained from all patients prior to participation. This study aims to provide a new and potentially more effective bladder-preserving treatment option for patients with high-risk/very high-risk NMIBC and to evaluate the safety profile of this combination regimen.
Eligibility: 18 Years to 75 Years · All · 1. Age 18-75 years.
2. Patients with a pathological diagnosis of high-risk or very high-risk non-muscle-invasive bladder cancer (NMIBC) following transurethral resection or cystoscopic biopsy.
"High-risk patients" must meet any one of the following criteria:
1. All T1 high-grade (HG)/G3 without carcinoma in situ (CIS), excluding those in the very high-risk group.
2. All CIS patients, excluding those in the very high-risk group.
3. Ta low-grade (LG)/G2 or T1 G1 without CIS, accompanied by three risk factors.
4. Ta HG/G3 or T1 LG without CIS, accompanied by at least two risk factors.
5. T1 G2 without CIS, accompanied by at least one risk factor. "Very high-risk patients" must meet any one of the following criteria:
(1) Ta HG/G3 with CIS accompanied by three risk factors. (2) T1 G2 with CIS accompanied by at least two risk factors. (3) T1 HG/G3 with CIS accompanied by at least one risk factor. (4) T1 HG/G3 without CIS, accompanied by three risk factors. (Risk factors: age \>70 years; tumor diameter \>3 cm; multiple papillary carcinomas) 3. No prior treatment with therapies targeting PD-1, PD-L1, PD-L2, or CTLA-4, or other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways (immune checkpoint blockers), or bacille Calmette-Guérin (BCG) therapy.
4\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ function, defined as meeting the following criteria (within 14 days prior to enrollment, without transfusion or granulocyte colony-stimulating factor treatment): "Hematology": i. Absolute neutrophil count (ANC) ≥1,000/mm³ ii. Platelet count ≥75,000/mm³ iii. Hemoglobin ≥8.0 g/dL "Hepatic function": i. Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin \>1.5 × ULN.
ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.
"Renal function": Creatinine clearance (CrCl) \>30 mL/min, calculated using the Cockcroft-Gault formula.
6\. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment, be willing to use effective contraception during the study period and for at least 6 months after the last dose of study drug (including chemotherapy agents and toripalimab). Male subjects with female partners of childbearing potential must agree to use effective contraception during the study period and for at least 6 months after the last dose.
7\. Subjects voluntarily agree to participate in the study by providing written informed consent, demonstrate good compliance, and are willing to cooperate with follow-up.
NCT06529822Phase 1Recruiting
Washington University School of Medicine · AdventHealth, Orlando, Florida
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.
Eligibility: 18 Years to · All · Inclusion Criteria Cohort #1:
* Age ≥ 18 years.
* ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
* Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter).
* Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern.
* Complete surgical resection of MIBC (R0) or upper tract urothelial carcinoma (renal pelvis and/or ureter). Tumor, nodes, metastases (TNM) classification (based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th ed.) at pathological examination of surgical resection specimen as follows: ypT0N0M0, pT2-4N0M0, or pT0-4aN+M0.
* Patient must have fully recovered from surgical resection in the opinion of the treating MD.
* ctDNA positive result as identified by Signatera.
* Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis.
* Adequate bone marrow and organ function as defined below:
* WBC ≥ 1.5 K/cumm
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 50 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN
* AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault
* The effects of synthetic long peptide personalized cancer vaccines and Hiltonol on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after completion of study interventions. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* No concurrent investigational therapies outside of this protocol are allowed.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria Cohort #1:
* Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy. Patients who have received perioperative neoadjuvant chemotherapy and immunotherapy, including enfortumab vedotin plus pembrolizumab (EV+P), are allowed.
* Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
* A psychiatric illness or social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record.
* Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for \> 7 consecutive days. Premedication for chemotherapy does not apply to this criterion and may be administered as per SOC practice. Any patients receiving steroids should be discussed with the PI to determine if eligible.
* Known HIV-positive status.
* History of positive test for Hep
NCT06896981Phase 2, Phase 3Recruiting
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh · Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Dhaka Division
Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder that is frequently associated with metabolic features, including obesity. Improvement of metabolic manifestations helps in the control of symptoms, including subfertility. Metformin has been commonly used to decrease insulin resistance and weight in PCOS patients suffering from obesity. Glucagon-like peptide (GLP-1) agonist semaglutide is also effective in managing different metabolic features, including obesity and insulin resistance. There is limited data about using a combination of semaglutide and metformin in women with PCOS suffering from obesity. This study aims to compare the metabolic changes after giving a combination of low-dose semaglutide and metformin vs. metformin alone over 12 weeks among women with PCOS and obesity. This open label randomized trial will be conducted in the Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU). After obtaining informed written consent, a total of 30 patients with PCOS and obesity will be enrolled conveniently (sampling) in the study as per inclusion and exclusion criteria from the outdoor, indoor, and PCOS clinic, Endocrinology, BSMMU. Study participants will be divided into two groups randomly by a computerized random number generator (allocation). One study arm will be treated with low-dose subcutaneous semaglutide (0.25 mg/week for 4 weeks followed by 0.5mg per week for 12 weeks) in combination with metformin (500 mg bid). Another study arm will receive monotherapy with metformin (500 mg bid) for treatment. Both arms will receive standard unified lifestyle advices. Patients will be followed every four weeks for clinical data for up to twelve weeks. Laboratory tests will be done at baseline and the final follow-up in an 8 - 12 hours of fasting state. Two mL of blood will be used to measure glucose using the glucose oxidase method on the same day of sample collection. The remaining three mL of blood will be centrifuged, the serum will be separated and analyzed for insulin, TT, SHBG, ALT and lipid profiles on the same day. All the clinical and biochemical information will be documented in a pretested, semi-structured case record form. Recorded data will be entered, edited, and analyzed by SPSS software version 25.0. Data will be expressed as frequencies \& percentages (%) for qualitative values and mean \& standard deviation (±SD) or median \& inter-quartile range (IQR) for quantitative values depending on their distribution. Kaplan Meier Curve will be used to show the comparison between primary outcomes. For quantitative variables, a comparison between two groups will be done using Mann-Whitney U test, and within a group, a paired t-test or Wilcoxon test will be used. For qualitative variables, a comparison between two groups will be tested using Pearson's chi-square test and within the group by the McNemar test. Regression Analysis will be done to correlate between treatment and outcome. Any p-value below 0.05 will be considered statistically significant. Confidentiality will be strictly maintained. Informed written consent will be taken from patients.
Eligibility: 10 Years to 45 Years · Female · Reproductive-aged women with PCOS diagnosed according to International evidence based guidelines 2023 and obesity
NCT07604766Phase 3Recruiting
Genmab · The First Hospital of Jilin University, Changchun
The purpose of this Chinese extension study is to compare how well Rina-S works against platinum-resistant ovarian cancer compared to chemotherapy drugs that are already approved and used for platinum-resistant ovarian cancer.
Treatment in this study could be Rina-S or it could be 1 of 4 indicated chemotherapy agents that are considered standard medical care. There is an equal (50:50) chance of getting Rina-S or an approved chemotherapy agent as treatment in this study. No one will know what treatment they are assigned to until the first dose.
All participants will receive active drug; no one will be given placebo.
This study is an extension study of the protocol GCT1184-02 (NCT06619236).
Eligibility: 18 Years to · Female · Key
* Participants must have histologically or cytologically confirmed high grade serous or endometrioid epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
* Participants may be enrolled regardless of FRα expression level.
* Participants must have received 1 to 4 prior lines of therapy. Participants must have progressed radiographically on or after their most recent line of therapy.
* Participants must have received prior treatment with the following therapies:
* Platinum chemotherapy
* Prior bevacizumab (or biosimilar) treatment is required, if labeled and available as standard of care per institutional guidelines, unless the participant has a documented contraindication or unless the participant is not eligible for treatment with bevacizumab (or biosimilar) due to precautions/intolerance
* Participants with known or suspected deleterious germline or somatic breast cancer gene (BRCA) mutations and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor as maintenance treatment unless the participant is not eligible for treatment with PARP inhibitor
* Mirvetuximab soravtansine, if:
* Mirvetuximab soravtansine is available in the enrollment region, and
* The participant is eligible, and
* The participant does not have a documented medical exception, including chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision.
* Participants must have platinum-resistant disease:
* Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum therapy, and must have either had a response (CR or PR) or had non-measurable disease at the start of adjuvant platinum-based therapy, and then progressed between \> 91 days and ≤ 183 days after the date of the last dose of platinum.
* Participants who have received a protocol defined number of lines of platinum-based therapy must have progressed on or within 183 days after the date of the last dose of platinum.
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