Clinical Research Directory

A Potential Relationship Between Treatment With Tyrosine Kinase Inhibitors and Erectile Dysfunction in Male Patients With Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome, resulting in the constitutive activation of the BCR-ABL1 tyrosine kinase. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the management of CML, trasforming it from a fatal disease to a chronic condition with excellent long-term outcomes for the majority of patients. The introduction of tyrosine kinase inhibitor (TKI) based treatment for CML has revolutionized the management of this previously fatal disease, achieving sustained disease-control in more than 90% of patients. However, as patients with CML are often required to undergo lifelong TKI therapy to maintain disease control, concerns regarding the long-term safety and tolerability of these agents have emerged. The efficacy of second and third-generation TKIs exceeds the efficacy of imatinib, owing to their potent impact on wild-type BCR-ABL1 and various BCR-ABL1 mutants, along with additional drug targets. Furthermore, TKIs exhibit activity on non-kinase targets (es. oxidoreductase NQO2 for nilotinib and imatinib). The prolonged treatment duration and expanded TKIs repertoire have led the emergence of various unexpected non-hematologic adverse events (AE), notably vascular adverse events (VAEs). Recent evidence indicates a relatively high incidence of severe arterial changes in TKI-treated patients, with VAEs frequency correlating with TKI dosage and treatment duration. However, data elucidating the clinical features of vascular events are lacking. Hormonal alterations have been reported in patients treated with imatinib. The tyrosine-kinase receptors cKIT and PDGF receptors, along with their respective ligands, are expressed in the testis, where they play a role in stimulating testosterone secretion by Leydig cells. Prolonged imatinib use has been associated with reduced testosterone production due to PDGFR and cKit blockade in the testis, potentially leading to gynaecomastia in men. Cardiovascular disease (CVD) remains the leading cause of mortality in the United States, accounting for nearly 40% of all deaths. CVD and ED share a variety of common risk factors, including hypertension, diabetes, dyslipidemia, smoking, obesity, physical inactivity, and metabolic syndrome. Screening and diagnosing ED hold significant potential for secondary prevention of CVD. Despite the estabilished association between ED and CVD, the precise mechanisms driving ED's predictive value for CVD are yet to be fully identified. Early deection and treatment of CVD during the critical time frame in which risk factors can be modified will effectively reduce the occurrence of fatal CV events in male patients with ED. This is a multicentre national, retrospective, prospective, non-interventional study that focuses on male CML patients starting first-line treatment with TKIs between 1 January 2015 and 31 January 2022. All enrolled patients will be involved in both retrospective and prospective evaluations. The retrospective component of the study allows the collection of data on the onset of ED, documented in medical records, that occurred before enrolment. It also includes information from physical examinations and laboratory tests, such as complete blood count, serum biochemistry (including renal and liver function tests, lipid profile and glycosylated haemoglobin), molecular biology for BCR-ABL transcript levels and electrocardiography (ECG), collected retrospectively every six months from enrolment until the documented onset of ED. The prospective evaluation assesses the occurrence of ED in the six months prior to enrolment and during the two-year follow-up period. The primary objective of the study is to assess the incidence of erectile dysfunction (ED) among male patients with chronic myeloid leukaemia (CML) undergoing treatment with tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, nilotinib, bosutinib or ponatinib, focusing in particular on those individuals who report the appearance of associated symptoms after treatment.

Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases

Leptomeningeal metastases (LM) are a relatively rare site of metastasis in advanced non-small cell lung cancer (NSCLC), and LM patients have a poor prognosis. Numerous retrospective studies have reported that high-dose Firmonertinib can also effectively increase patient prognosis and have tolerable side effects, but there is a lack of prospective studies to confirm this. In addition, there are currently no good biomarkers for monitoring the efficacy of LM treatment. cfDNA testing can be used for early cancer screening, monitoring tumor progression, evaluating treatment response, and discovering drug resistance mechanisms. Due to the influence of the blood-brain barrier, the level of cfDNA in the plasma of LM patients is often very low, and the detection of cfDNA in cerebrospinal fluid (CSF) is more advantageous. Therefore, exploring the dynamic monitoring of LM treatment efficacy using CSF cfDNA is of great significance for improving patient prognosis. Based on this, the applicant intends to conduct a prospective, multicenter, single-arm, post-market exploratory clinical trial on the treatment methods and efficacy monitoring of NSCLC-LM patients. The aim was to explore whether cfDNA has the potential to become a biomarker for LM efficacy monitoring and to validate the efficacy and safety of high-dose fumatinib combined with intrathecal injection in the treatment of NSCLC-LM patients.

Neoadjuvant Befotertinib Combined Bevacizumab or Platinum-based Double Chemotherapy for Resectable Locally-advanced EGFR Mutation-positive Non-Small Cell Lung Cancer

This study targeted patients with resectable stage II-IIIA non-small cell lung cancer with EGFR mutation

Anlotinib Plus Nab-Paclitaxels and S-1 for Patients with Advanced Biliary Tract Cancer As Second-Line Treatment

Biliary tract cancer (BTC) presents with a 5-year survival rate less than 5%. The goal of this clinical trial is to evaluate if Anlotinib plus Nab-Paclitaxels and S-1 as second-line regimen can improve the treatment efficacy in advanced biliary tract cancer (BTC) after progression upon first-line standard treatment, in comparison with standard second-line FOLFOX regimen.

Olverembatinib as Maintenance Therapy or Preemptive Therapy After Allo-HSCT in Ph+ALL

This study is a single-center, prospective, single-arm exploratory study. Ph + acute lymphoblastic leukemia patients treated with allogeneic hematopoietic stem cell transplantation were recruited from the Stem Cell Transplantation Center of the Hospital of Hematology, Chinese Academy of Medical Sciences. The number of patients is expected to be 50 cases. The enrolled patients plan to receive Olverembatinib as a post-transplant treatment regimen, including maintenance therapy to prevent recurrence and preemptive treatment. Hematopoietic reconstitution ( neutrophil \> 0.5 × 10 \^ 9 / L, platelet \> 50 × 10 \^ 9 / L ) was evaluated after enrollment. From 2 months to 3 months after transplantation, Olverembatinib 40 mg QOD was added for maintenance treatment until 2 years after transplantation. During maintenance treatment, Olverembatinib dose ( dose range 20 mg QOD to 40 mg QOD ) can be adjusted according to blood picture, biochemical index or other oral drugs ( triazole drugs, etc. ).

HAIC in Combination with Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Advanced HCC

The purpose of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) in combination with PD-1 inhibitors and Lenvatinib in patients with different tumor burden advanced-stage hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

SBRT Combined With Adbelimumab and Apatinib for Perioperative and Conversion Therapy of Hepatocellular Carcinoma

This is a Phase II , Open-label , Investigator-initiated Trail of SBRT in Combination With Adbelimumab and Apatinib in Patients With Hepatocellular Carcinoma(HCC).This study aims to evaluate the safety and efficacy of SBRT in Combination With Adbelimumab and Apatinib as a preoperative and conversion treatment of HCC.

Anlotinib Combined With Carboplatin/Paclitaxel as First-line Treatment in Patients With Advanced Ovarian Cancer

It has been reported that antiangiogenic drugs combined with chemotherapy as first-line treatment, and subsequent antiangiogenic drugs as maintenance therapy for ovarian cancer can achieve better clinical benefits. Therefore, this study is expected to investigate the efficacy and safety of anlotinib combined with carboplatin/paclitaxel as first-line treatment in patients with advanced ovarian cancer.

ProSpecTive sAmpling in dRiver muTation Pulmonary Oncology Patients on Tyrosine Kinase Inhibitors (START-TKI)

The study is perfomed with adult patients with non-small cell lung cancer treated with tyrosine kinase inhibitor. The objective is to collect repeated samples of blood from patients (starting) on a tyrosine kinase inhibitor, for liquid mutation testing, and pharmacokinetic analysis.