Clinical trials

Surgical intervention remains the primary treatment option for early-stage lung cancer. With the proven efficacy of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), neoadjuvant immunotherapy has increasingly become a focal point of research. Blocking vascular endothelial growth factor (VEGF) not only inhibits the proliferation of vascular endothelial cells and the formation of new blood vessels but also improves the tumor microenvironment and enhances the infiltration of cytotoxic T lymphocytes within it. Simultaneously targeting the VEGF and PD-L1 pathways can create a synergistic anti-cancer effect. PM8002 injection is a bispecific antibody drug that targets both PD-L1 and VEGF, functioning as a dual-action agent that combines immune suppression and anti-angiogenesis. In patients with locally advanced stage II-III NSCLC, neoadjuvant therapy that concurrently targets PD-L1/VEGF in combination with chemotherapy can improve pathological response rates, provided that the safety of the drug combination is maintained. This approach offers additional benefits to patients, prolongs event-free survival (EFS), and improves prognosis.

This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival. After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.

Chronic arthropathy is one of the most common complications of haemophilia, affecting up to 90 per cent of patients aged 4 and over in at least one joint. the study aims to assess gene expression in biological samples collected via synovectomy and joint replacement surgery, as well as in peripheral blood, in patients with severe haemophilia A or B; to compare these data with those from patients with osteoarthritis and rheumatoid arthritis; and to correlate the gene expression data with information relating to the clinical and laboratory phenotype, the history of inhibitors, and ultrasound and histological findings.

OLIGAMI trial is a multi-institutional, two-arm, open-label, randomized controlled phase III trial being conducted with the participation of 50 hospitals belonging to Japan Clinical Oncology Group. After the first registration, all patients will be performed in a 12-week, subtype-specific, systemic therapy consisting of CDK4/6 inhibitors with hormonal therapy for luminal BC, docetaxel with trastuzumab and pertuzumab for HER2-positive BC, chemotherapy with immune checkpoint inhibitors for triple-negativeBC expressing PD-L1, and olaparib for cases harboring BRCA mutations. For other triple-negative BC, chemotherapy will be administered. If this 12-week systemic therapy does not cause any progression or complete response, patients proceed to second registration for randomization; arm A continues same systemic therapy alone, and arm B performs MDT followed by same systemic therapy. The MDT will involve either RT or surgery, and RT will involve mainly SBRT and partly conventional RT.

Esophageal cancer (EC) ranks among the leading malignant gastrointestinal tumors globally in terms of both incidence and mortality. Cases of EC in China account for over 50% of the global total, with squamous cell carcinoma being the primary pathological type. Locally advanced EC (LAEC), particularly cases where radical surgical resection is not feasible, exhibits high recurrence rates and low 5-year survival rates. However, studies have shown that patients with LAEC who undergo comprehensive treatment followed by surgery experience significantly prolonged survival and improved quality of life compared to those who do not receive surgical intervention. Current conversion treatment regimens under investigation include: chemotherapy alone, chemoradiotherapy, immunotherapy combined with chemotherapy, and immunotherapy combined with chemoradiotherapy-each of these approaches has distinct advantages and limitations. Immunochemotherapy has emerged as a current research focus: it not only demonstrates significantly superior efficacy compared to chemotherapy alone but also exhibits lower cumulative toxicity than radiotherapy-combined conversion regimens, resulting in a more favorable overall benefit-risk ratio. As such, it represents the most promising conversion treatment strategy. Retrospective and prospective clinical studies have shown that low-dose radiotherapy targeting the small intestine can enhance the anti-tumor response of immune checkpoint inhibitors (ICIs) in patients with advanced solid tumor, prolong their overall survival, and increase the incidence of the abscopal effect. Further mechanistic investigations have revealed that intestinal low-dose radiotherapy (ILDR) may augment the immune cancerous lethality by modulating the gut microbiota and their metabolic profiles. Based on the findings from these preliminary studies, the current research plans to conduct a prospective phase II single-arm clinical trial to investigate the efficacy and safety of ILDR combined with immunochemotherapy as conversion therapy in patients with borderline resectable or unresectable esophageal squamous cell carcinoma (BR/UR ESCC). This research plans to enroll at least 39 evaluable cases or a total of 39 cases in two seperated stages, focusing on patients with thoracic BR/UR ESCC. Patients will receive a single fraction of ILDR with a mean dose of 1 Gy, concurrently with 3 cycles of albumin-bound paclitaxel (260 mg/m² on day 1), cisplatin (75 mg/m² on day 1), and tislelizumab (200 mg on day 1). The efficacy and safety of the treatment will be evaluated throughout the study.

With the title of "Long-Term Outcomes of endoscopic-assisted vs conventional breast-conserving surgery in breast cancer patients after neoadjuvant therapy: a randomized, multicenter, open label, non-inferiority trial", this study targets breast cancer patients after neoadjuvant therapy. A total of 804 eligible patients, after screening with inclusion and exclusion criteria, will be randomly assigned to Endoscopic-assisted breast conserving surgery(E-BCS) or conventional breast conserving surgery (C-BCS) group at a 1:1 ratio using stratified block randomization method, stratified by centers and molecular subtype. The co-primary endpoints are 5-year disease-free survival (5y-DFS) and Breast-Q score at 6 months after surgery. The secondary endpoints are cosmetic outcomes including surgeons' satisfaction with breast and patients' satisfaction with scar, survival outcomes including 5-year overall survival (5y-OS) and 5-year local-recurrence rate (5y-LRR), surgical outcomes including operative time, intraoperative blood loss, incision length and postoperative complications rate. This study aims to confirm the long-term safety and aesthetic outcome of endoscopic-assisted surgery in breast cancer patients after neoadjuvant treatment by comparing it with conventional open breast conserving surgery, and provide clinical evidence for the popularized application of endoscopic breast surgery.

This is an open-label, phase II study that may provide evidence that taking S-adenosylmethionine (SAMe) supplementation prevents oxaliplatin, a type of chemotherapy drug, associated liver toxicity in patients with resectable colorectal liver metastases. Resectable means that it is able to removed with surgery. Patients will take two SAMe tablets in the morning and one tablet in the evening for 3-6 months (about 6-8 cycles of chemotherapy) in addition to oxaliplatin based chemotherapy followed by surgical removal of the colorectal liver metastases.

This study aims to evaluate the accuracy of augmented reality (AR)-assisted dental procedures. Patient-specific anatomical data will be acquired using cone-beam computed tomography (CBCT) and intraoral scanning and integrated to create a three-dimensional virtual model for treatment planning. Different dental procedures, including tooth extractions, dental implant placement, and orthodontic procedures, will be virtually planned before treatment. During the clinical procedure, the planned anatomical and procedural information will be visualized through an AR system, providing real-time guidance to the operator. The accuracy of AR-assisted treatment will be assessed by comparing the preoperative virtual plan with the postoperative clinical outcome, evaluating deviations between planned and achieved results.

standard paradigm for management of patients who present with concern for recurrence of brain metastases following initial stereotactic radiosurgery (SRS).

This is a multicenter randomized controlled trial including patients with small (\<2 cm) suspected or confirmed thyroid cancers. Patients are included after informed consent and randomized to one of two treatments. One treatment is a standard henithyroidectomy and the second treatment is radiofrequency ablation (RFA) of the specific tumor. The investigators will evaluate initial outcome of the allocated treatment, thyroid hormonal function, oncologic safety, quality of life, and treatment costs in a follow-up period of five years after treatment. The overall aim of the study is to improve patient's health by reducing the number of operations on small thyroid cancers. In patients with these small tumors, the long-term adverse outcome may be higher than possible benefits from the operation. For participants undergoing surgical treatment with HT, the investigators will measure final histology and both beneficial and adverse outcome from the operation. For participants undergoing RFA, the investigators expect to reduce the need for thyroid hormonal substitutions, reduce the surgical adverse outcomes, reduce treatment costs and increase QoL without a reduction in oncologic safety and outcome.

Patients with oligoprogression of metastatic breast cancer during palliative treatment that is amenable to local therapy will be included. The local ablative therapy (LAT) may consist of stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy, surgery or percutaneous ablation.

Purpose of the Study: This clinical study investigates whether a shorter or longer duration of systemic therapy before local treatment (surgery or radiation) results in better disease control in patients with esophageal or gastric cancer with a limited number of metastases, also known as oligometastases. Background: In about 25% of patients with advanced esophageal or gastric cancer, the disease spreads to only a few sites (oligometastatic disease). Prior studies suggest that local treatment after systemic therapy may extend survival in this subgroup. However, it is unclear how long systemic therapy should last before initiating local treatment. The OMEC-5 study aims to clarify this. Study Design: Initiated by Amsterdam UMC and UMCU and conducted in multiple hospitals across Europe. Total of 414 patients to be enrolled. Duration: \~53 months (35 months enrollment + 18 months follow-up). Approved by the medical ethics committee at Amsterdam UMC. Procedure: Eligibility screening: Includes physical exam, blood tests (incl. circulating tumor cells), medical history review, and confirmation of oligometastases by an expert panel. Initial treatment: All participants receive 4 months of standard systemic therapy (chemotherapy + immunotherapy and/or targeted therapy depending on tumor markers like HER2 or Claudin 18.2). Response assessment (Review 1): Imaging and/or laparoscopic examination. If oligometastases persist and tumors have not progressed, participants are randomized into two groups: Group A (longer systemic therapy): 4 more months of systemic therapy, then local treatment if disease is stable, followed by 4 months of immunotherapy ± targeted therapy. Group B (shorter systemic therapy): Immediate local treatment followed by 4 months of systemic therapy, then reassessment and potentially 4 months of immunotherapy ± targeted therapy. Follow-up: Regular scans and quality-of-life questionnaires (5 times), and periodic blood sampling (4 times). Treatments Involved: Chemotherapy: CapOx or FOLFOX Immunotherapy: nivolumab or pembrolizumab Targeted therapy: trastuzumab (HER2-positive) or zolbetuximab (Claudin 18.2-positive) Potential Benefits and Risks: Patients may benefit from better disease control and a personalized treatment strategy. Known side effects relate to the standard treatments used (chemo, immuno, targeted therapies), and no extra medical risk is expected beyond routine care. Possible inconveniences include blood draws, scans, minor surgery (laparoscopy), and time investment. Data and Sample Handling: Personal data and tumor/blood samples for exploratory research (if patients consent) are coded and securely stored. Data may be used for future cancer research if the patient consents. Participants can withdraw at any time. Confidentiality and Privacy: Patient data are kept confidential, and participants have rights to access or delete their data. Privacy measures comply with GDPR and Dutch law. Compensation and Insurance: Participation is voluntary, with no financial compensation. Standard treatment costs are covered by healthcare insurance. No extra insurance is required, as the treatment aligns with standard care practices.

The aims of the Observational Approach versus Surgical Intervention for Asymptomatic Stone (OASIS) trial are: 1) to determine whether observation compared to upfront surgery results in less healthcare-related life disruption due to kidney stones among children and adults with asymptomatic kidney stones; 2) to identify the groups benefiting the most from each strategy; and 3) to determine the preferences and values informing the choice between observation and upfront surgery.

This study is a single-arm prospective clinical trial. The primary objective of the study is to explore the efficacy and safety of preoperative neoadjuvant therapy with Tislelizumab combined with Anlotinib and Nab-Paclitaxel in resectable stage III non-small cell lung cancer.Finally, it provides new evidence-based medical evidence for the perioperative treatment of non-small cell lung cancer.

Over 60% of head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at a locally advanced stage. While standard treatments involve surgery and chemoradiotherapy, prognosis remains poor, with 50-60% experiencing local recurrence within two years. Neoadjuvant therapy can potentially reduce tumor burden, preserve organs, and lower distant metastasis risk. Despite the KEYNOTE-689 trial showing that adjuvant two-cycle pembrolizumab increased major pathological response to 9.8% in stage III-IVB HNSCC, this result remains insufficient. More effective immunotherapy-based combinations are urgently needed to improve long-term survival after neoadjuvant treatment. Preclinical and clinical evidence indicates that low-dose radiotherapy can activate the tumor immune microenvironment and synergize with immunotherapy. Based on this rationale, the present clinical trial will evaluate a neoadjuvant regimen combining LDRT with two cycles of an anti-PD-1 inhibitor in patients with surgically resectable, locally advanced HNSCC.

Head and neck paragangliomas (HNPGs) are predominantly non-secreting, benign and slow-growing tumors. Although most patients remain asymptomatic, up to 30% develop symptoms related to local tumor growth and fewer than 5-10% develop metastatic disease. Surgery has long been considered the standard treatment, while radiotherapy and active surveillance represent alternative management strategies. Treatment-related morbidity and impaired quality of life have been reported in patients with HNPGs; however, the impact of immediate intervention compared with an initial active surveillance strategy has not been prospectively evaluated. This multicenter randomized controlled trial aims to compare active surveillance with immediate intervention in patients with newly diagnosed carotid or vagal paragangliomas. The study hypothesis is that an initial active surveillance strategy increases the time before functional outcome deterioration, particularly ENT-related symptoms, while not resulting in a higher complication rate when treatment is subsequently performed. Eligible patients will undergo baseline assessment including a specialized ENT examination to evaluate cranial nerve function and cervical MRI (or contrast-enhanced CT when MRI is contraindicated) to confirm tumor location, size, and the absence of lymphadenopathy or atypical imaging features. After providing written informed consent, participants will be centrally randomized in a 1:1 ratio, stratified by study center and tumor location, to either active surveillance or immediate intervention. Patients assigned to active surveillance will undergo regular clinical and radiological follow-up, with treatment initiated only if disease progression or symptom development warrants intervention. Patients assigned to immediate intervention will receive surgery or radiotherapy according to multidisciplinary team recommendations and local practice, within six months after randomization. Patients who decline participation in the randomized trial, as well as those who are not eligible for randomization, may be offered participation in a parallel observational study collecting clinical, imaging, treatment and outcome data according to routine practice. Patient quality of life will also be assessed throughout the study (experimental and observational) using validated questionnaires.

This is a non-comparative randomized Phase 2 study using the INITIUM regimen with or without elective nodal irradiation (ENI) delivered before surgery for resectable head and neck squamous cell carcinoma (HNSCC).

The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) followed by nab-paclitaxel combined with toripalimab in patients with previously untreated HR+/HER2-negative breast cancer. Eligible patients include those with stage IIB-IIIC disease (cT3N0, cT2-4N1-3 or cT1N2-3) or stage IIA disease (cT2N0 or cT1N1) with at least two of the following high-risk factors: histologic grade 3, Ki-67 ≥50% or premenopausal with age \<50 years. A total of 27 enrolled patients will be assigned to receive the combination therapy. The primary question it aims to answer is whether this combination of radiotherapy, de-escalated chemotherapy, and immunotherapy can improve the total pathologic complete response (tpCR) rate (defined as ypT0/Tis ypN0).

This study is being done to answer the following question: Are there types of early-stage vulvar cancer that require either less or more treatment than the usual approach?

This multicenter, randomized, open-label, parallel-controlled clinical trial aims to evaluate the efficacy and safety of surgery combined with postoperative chemoradiotherapy versus finotonlimab plus induction chemotherapy followed by postoperative finotonlimab maintenance therapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).

Primary Objectives： Evaluate the complete response rate (CR rate) and safety of short - course radiotherapy combined with ivonesimab (AK112) in patients with pMMR/MSS mid - low rectal cancer. Secondary Objectives： Evaluate treatment - related toxic reactions, the quality of life, long - term prognosis (local control \[LC\], disease - free survival \[DFS\] and overall survival \[OS\]). Patients will : Receive Radiotherapy: Pelvic IMRT or VMAT, DT 25Gy/5Fx. One week after radiotherapy, begin treatment with Ivorsimab (AK112) at a dose of 20mg/kg by intravenous drip on day 1. One cycle is 21 days, and a total of 6 cycles are to be carried out. Evaluate the curative effect after 3 cycles of treatment. Patients with progressive disease (PD) will withdraw from the study, and other treatment plans will be adjusted in a timely manner. Patients with CR/PR/SD will continue treatment for another 3 cycles. Conduct a comprehensive assessment after 6 cycles of treatment. Patients who achieve cCR can choose the watch - and - wait approach. For patients who do not achieve cCR, TME surgery is recommended. Decide whether to perform adjuvant chemotherapy based on the postoperative pathological findings.

Exploring the therapeutic effect of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab on advanced stage III-IV endometrial cancer

This is a prospective, randomized, open-label, two-arm phase 2 trial that will evaluate whether the use of Pulsed Low-Dose-Rate radiation technique, as compared to standard radiation, is associated with reduced rates of clinically significant esophagitis during and following chemoradiation.

This is a prospective, open-label, single-center, single-arm phase II clinical trial evaluating the efficacy and safety of multimodal ablation in combination with perioperative tislelizumab and chemotherapy in patients with pathologically confirmed resectable stage II-IIIB (N2) non-small cell lung cancer (NSCLC).

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. Oropharynx SCC (OPSCC) is a common sub-type of HNSCC. Each year, 16,000 new cases of OPSCC are diagnosed in the USA. Most cases of OPSCC (\>90%) are caused by the human papillomavirus (HPV) and are often cured with current therapy. However, patients treated with surgery followed by postoperative adjuvant chemotherapy and radiation therapy (POA(C)RT) still experience substantial morbidity. In this highly curable disease, current clinical research interest is focused on investigation of de-escalated therapy, with the goal to reduce treatment-related adverse events (AEs) while maintaining a low recurrence rate. In this study, patients with HPV-related OPSCC will undergo resection of the primary tumor site and involved/at-risk regional neck nodes. Based on the pathology report, patients will be assigned to: * Arm 1 (de-POACRT-42 Gy) * Arm 2A (de-POART-42 Gy) * Arm 2B (de-POART-37.8 Gy) * Arm 2C (de-POACRT-30 Gy). All patients with high-risk pathology will be assigned to Arm 1 whereas patients with intermediate-risk pathology will be randomized (1:1:1) to Arm 2A, Arm 2B, or Arm 2C. Patients with highest-risk pathology and low-risk pathology will be removed from the trial after surgery and will be advised to pursue standard of care options.