Clinical Research Directory

Sequential Chemotherapy Followed by Ultrahypofractionated Radiotherapy for Muscle-Invasive Bladder Cancer

Muscle-invasive bladder cancer (MIBC) is a potentially lethal disease for which radical cystectomy with appropriate systemic therapy remains a standard curative approach in medically fit patients. . However, Half of bladder cancer cases are diagnosed in patients aged over 75 years, many of whom are not fit for major surgery owing to their performance status and comorbidities . A substantial proportion of bladder cancer cases occur in older adults (there is no single universal age cutoff for the term older adults, but several commonly used definitions exist: WHO: generally refers to people aged 60 years or older, particularly in low- and middle-income countries, while in clinical and research settings: ≥65 years is frequently used as the operational definition of older adults, especially in oncology and geriatric medicine), and advanced age is frequently accompanied by comorbidities and frailty that may limit eligibility for radical surgery or multimodality treatment . Bladder-preserving treatment incorporating maximal transurethral resection of bladder tumor (TURBT) and definitive radiotherapy is therefore an important treatment option in selected patients.

Treating Muscle-invasive Bladder Cancer With A Non-surgical Method Consisting of Anti-PD-1 Therapy and Chemoradiation

The goal of this Phase 2 trial is to evaluate a non-surgical bladder-preserving treatment mode which consists of neoadjuvant chemotherapy plus anti-programmed cell death protein 1 (anti-PD-1) therapy followed by radiotherapy plus concurrent anti-PD-1 therapy. The main questions it aims to answer are: (i) whether the anti-PD-1 antibody, toripalimab, is effective in treating muscle-invasive bladder cancer (MIBC), when combined with chemoradiation; (ii) whether toripalimab is safe in combination with chemoradiation. Participants will receive 3 cycles of neoadjuvant treatment containing chemotherapy with gemcitabine and cisplatin/carboplatin, plus toripalimab. Then the ones without progressive disease will receive radical radiotherapy plus 2 cycles of concurrent toripalimab.

DAHANCA 33: Image Guided Dose-escalated Radiotherapy to Patients With Hypoxic HNSCC

Aim: To improve curability of radiotherapy in HNSCC patients identified by hypoxic FAZA-PET scanning

DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC.

Hypoxic modification of radiotherapy with nimorazole has previously been shown to increase radiosensitivity in hypoxic head and neck squamous cell carcinomas (HNSCC). In Denmark, nimorazole is added the radiotherapy of most HNSCC, as it has not previously been possible to discriminate more hypoxic tumours from less hypoxic tumours. A hypoxia gene profile has shown to discriminate between responders and non-responders to nimorazole. In DAHANCA 30, expected hypoxia profile guided non-responders are randomized to +/- nimorazole during radiotherapy.This in order to verify clinical use of the gene profile in selecting the relevant patients for hypoxic modification of radiotherapy with nimorazole.

PRaG-1 Plus PRaG Therapy in in Elderly Patients With Advanced Solid Tumors: A Prospective Clinical Trial (PRaG 10.0)

The goal of this clinical trial is to learn if a combination treatment using PRaG-1 Cordycepin Tablets with radiation therapy, immune-boosting injections, and immunotherapy drugs can help patients with advanced solid tumors. It will also assess safety. The main questions it aims to answer are: Does this treatment improve immune function and slow tumor growth? What side effects or risks occur during treatment? Participants will: Take PRaG-1 Cordycepin Tablets (a natural compound derived from Cordyceps fungus) orally: higher dose for 7 days before radiation, then lower daily dose for 2 weeks Receive targeted radiation therapy to the tumor area (5-12 Gy total in 2-3 sessions) Get daily immune-boosting injections (GM-CSF) for 7 days starting with radiation Receive immunotherapy drugs (PD-1/PD-L1 inhibitors) within one week after radiation Have blood drawn and small tumor tissue samples taken before and after the first two treatment cycles for immune analysis All participants will receive this combination treatment; there is no placebo or alternative treatment group in this study.

Phase II Study of Primary Tumor Resection and Selective Lymph Node Dissection Followed by RT for BTC With Lymph Node Metastases

This is a multicenter, open-label, single-arm, prospective phase II clinical study. Eligible patients with lymph node-positive biliary tract cancer will undergo primary tumor resection with selective lymph node dissection. During surgery, the regional and retroperitoneal lymph nodes will be explored, and lymph nodes that are technically amenable to surgical resection will be dissected. Metastatic lymph nodes that cannot be safely or completely resected because of local invasion or because of their location beyond the feasible surgical dissection field will not be surgically resected and will subsequently be treated with postoperative radiotherapy. Following surgery, patients will receive postoperative radiotherapy to the primary tumor bed and involved/regional lymph node areas. For patients who undergo R0 or R1 resection, concurrent chemoradiotherapy with capecitabine or S-1 will be administered for 2 cycles, followed by 6 cycles of adjuvant chemotherapy. For patients who undergo R2 resection, concurrent radiotherapy with capecitabine or S-1, with or without a PD-1/PD-L1 inhibitor, will be administered, followed by maintenance therapy with capecitabine or S-1, with or without a PD-1/PD-L1 inhibitor, until disease progression or unacceptable toxicity.

BITS-TO-HCC Study: HAIC+Iparomlimab/Tuvonralimab + Bevacizumab + Surgery/SBRT for BCLC-C HCC With PVTT and/or Oligometastases

This single-center, prospective, single-arm Phase II clinical trial is designed to evaluate the efficacy and safety of combining hepatic artery infusion chemotherapy (HAIC, for up to 4 cycles) with iparomlimab/tuvonralimab plus bevacizumab followed by multidisciplinary team (MDT) evaluation for surgical resection or stereotactic body radiotherapy (SBRT) in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) who present with portal vein tumor thrombus (PVTT) or extrahepatic oligometastatic disease. The study aims to determine whether this combination strategy can prolong progression-free survival (PFS), while also improving overall survival (OS), objective response rate (ORR), disease control rate (DCR), and local control rate (LCR), and evaluate the conversion rate to surgical resectability, as well as maintaining quality of life (QoL). In addition, the trial will systematically evaluate the safety profile and treatment-related toxicities associated with this regimen.

Continuation of First-line Therapy With Radiotherapy Versus Early Switch to Second-line Therapy in Oligoprogressive HCC

This multicenter, prospective, randomized, controlled, open-label, two-arm Phase III clinical trial is designed to evaluate whether adding radiotherapy to oligoprogressive lesions while continuing first-line systemic therapy at the time of oligoprogression can effectively prolong progression-free survival compared to early switching to second-line systemic therapy in oligoprogressive hepatocellular carcinoma.

Hypofractionated LocoRegional Radiotherapy in Breast Cancer

The primary objective of this study is to determine if hypofractionated RT delivered over 1 week to the breast or chest wall and regional nodes (26Gy in 5 daily fractions) following BCS or mastectomy, is non-inferior to conventional fractionation to the breast or chest wall and regional nodes delivered over 3 weeks (40Gy in 15 daily fractions) in patients with node-positive breast cancer.

Trastuzumab Rezetecan Combined With Radiotherapy Versus Trastuzumab Rezetecan in the Treatment of HER2-positive Advanced Breast Cancer With Brain Metastases

A total of 224 subjects of HER2-positive advanced breast cancer with brain metastases are planned to be enrolled. Eligible subjects will be randomly assigned in a 1:1 ratio to the group receiving Trastuzumab Rezetecan combined with radiotherapy or the group receiving Trastuzumab Rezetecan monotherapy until disease progression, intolerable toxicity, withdrawal of informed consent, or the study determines that treatment must be terminated (whichever occurs first).

Nutritional Status of Head and Neck Cancer Patients

This study aims to monitor the nutritional status of patients with head and neck cancer undergoing radiotherapy treatment. Throughout the treatment process, patients' body composition, handgrip strength, food intake, quality of life, and treatment-related side effects will be regularly assessed. Measurements will include physical parameters like body weight, height, and waist circumference, as well as blood test results and nutrition-related questionnaires. By closely tracking these changes, the study seeks to identify early signs of nutritional deterioration and support timely interventions. The goal is to better understand nutrition-related challenges during treatment and ultimately improve patients' quality of life.

Efficacy and Safety of Concurrent PD-1 Inhibitor and Radiotherapy With Immunonutrition for Esophageal Squamous Cell Carcinoma

At present, concurrent chemoradiotherapy (cCRT) with platin-based dual-drug regimen is the standard treatment for inoperable, locally advanced esophageal cancer in patients with a good performance status. However, cCRT has substantial toxic effects, and a large number of patients with older age, malnutrition and other morbidities, cannot tolerate cCRT. Several phase II trials showed combining PD-1 inhibitor with definitive cCRT provided encouraging activity and acceptable toxicity in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Therefore, this single-arm, multicenter, phase II trial aims to assess the efficacy and safety of immunotherapy plus radiotherapy with immunonutrition support in patients with LA-ESCC and positive PD-L1 expression who are intolerant to cCRT.

A Prospective, Biomarker-Stratified Phase 2 Study: β-Hydroxybutyrate as a Predictive Biomarker for Short-Course Radiotherapy Followed by Chemotherapy Plus PD-1 Inhibitor Versus Chemotherapy Alone in Locally Advanced Rectal Cancer

This is a prospective, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Patients are stratified into an β-HB-positive stratum (elevation significantly) and an β-HB-negative stratum (no elevation), then randomized 1:1 within each stratum to receive either perioperative chemotherapy plus PD-1 inhibitor or perioperative chemotherapy alone. The primary endpoint is the complete response (CR) rate, defined as the composite of pathological complete response (pCR) and clinical complete response (cCR). The study aims to evaluate the efficacy and safety of adding PD-1 inhibitor to perioperative chemotherapy in LARC, and to validate post-radiotherapy β-HB elevation as a predictive biomarker for immunotherapy benefit.

Intestinal Low-Dose Radiotherapy Plus Immunochemotherapy for Conversion of Borderline Resectable/Unresectable Esophageal Squamous Cell Carcinoma

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.

Photon Radiotherapy Plus Tremelimumab/Durvalumab for BCLC Stage B and C HCC

Tremelimumab plus durvalumab (the STRIDE regimen) is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC); however, it demonstrates limited efficacy, with an objective response rate (ORR) of only 20.1%. Radiation therapy (RT) is highly effective in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Preclinical studies have shown that combining RT with PD-L1/PD-1 blockade promotes immunogenic cell death and enhances antigen presentation by dendritic cells, thereby boosting systemic T cell-mediated antitumor responses in mouse models. The addition of CTLA-4 inhibition further enhances antigen cross-priming following RT. Recent retrospective data also indicate that combining RT with immune-oncology agents is associated with improved overall survival and prolonged time to progression compared to RT or immunotherapy alone. However, the clinical benefit and immunologic impact of combining RT with tremelimumab and durvalumab have not yet been evaluated in prospective clinical trials for unresectable HCC. This phase II, single-arm clinical trial aims to assess the safety, efficacy, and immunologic effects of combining proton RT with tremelimumab and durvalumab in patients with unresectable HCC.

Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer (MODIFI-RC-II)

Most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) and respond poorly to PD-1 inhibitors. Radiotherapy can enhance tumor antigen release and improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes (TDLNs) are critical sites for anti-tumor immune activation, but radiation-induced damage and fibrosis may impair lymphatic drainage and immune responses. Previous studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This study aims to evaluate whether node-sparing short-course radiotherapy followed by sequential chemotherapy and PD-1 blockade can improve complete response rate in the phase II part and event-free survival in phase III part, together with sphincter preservation, treatment tolerance, and prognosis in patients with mid-low pMMR/MSS rectal cancer.

Radiotherapy Combined With PD-1 Monoclonal Antibody and Capecitabine in the Treatment of Nasopharyngeal Carcinoma

This is a single-arm, multicenter, prospective, open-label phase II clinical trial of multi-target radiotherapy combined with PD-1 monoclonal antibody and capecitabine maintenance therapy treating oligometastatic nasopharyngeal carcinoma, the main purpose of which is to evaluate the efficacy of multi-target radiotherapy combined with PD-1 monoclonal antibody and capecitabine maintenance therapy regimen in treating oligometastatic nasopharyngeal carcinoma.

Risk Factors of Jaw Osteoradionecrosis in Oral Cavity Cancer Patients Post-Radiotherapy

Osteoradionecrosis (ORN) of the jaw is a serious complication that can occur after radiation therapy for head and neck cancers, including oral cavity cancer (OCC). ORN happens when jawbone tissue dies and fails to heal, often triggered by dental issues like tooth extractions or poorly fitting dentures. Symptoms can include exposed bone, pain, difficulty opening the mouth, trouble swallowing, and even jaw fractures-leading to major physical and emotional challenges. The likelihood of ORN varies widely, from less than 1% to over 50% in head and neck cancer patients. For OCC specifically, studies report rates from 4% up to 25%. Treatment depends on how much bone is affected and can range from medication to major surgery. Risk factors include radiation dose, tumor location, oral health, dental extractions, lifestyle habits (like alcohol use), and other health conditions. Poor oral hygiene, high radiation doses, and alcohol use are among the most common risks. However, current data on OCC patients is limited and often not broadly applicable. This study will retrospectively examine what increases the risk of ORN in OCC patients who received radiation therapy before or after surgery. Using data from multiple international centers, it aims to identify patterns and provide globally relevant insights. The results will help guide prevention strategies and create evidence-based guidelines to reduce ORN and improve long-term outcomes for these patients.

Low-dose Thoracic Radiotherapy Followed by Adebrelimab Plus Chemotherapy, and Then Sequential Maintenance Therapy With Adebrelimab for Extensive-stage Small Cell Lung Cancer

This study is a multicenter, prospective investigation aiming to evaluate the efficacy and safety of low-dose radiotherapy (15Gy/1.5 Gy bid × 10 fractions) combined with 4-6 cycles of systemic chemotherapy concurrently with Adebrelimab, followed by Adebrelimab maintenance therapy for up to two years, in subjects with extensive-stage small cell lung cancer (ES-SCLC). Additionally, immunohistochemical detection of the expression levels of four key transcriptional proteins-YAP1, NEUROD1, ASCL1, and POU2F3-will be performed to guide the molecular subtyping of SCLC. Based on these findings, we will explore the differential therapeutic outcomes of this regimen across distinct molecular subtypes (A/N/P/Y/I/AN/QN), with the goal of identifying the subject population most likely to benefit from this treatment modality, thereby optimizing clinical decision-making.

The Effect of Radiotherapy After Separation Surgery for Spinal Metastases

The aim of this clinical study is to explore the impact of whether radiotherapy is administered after spinal metastasis surgery on the prognosis and survival of patients, to describe the clinical outcomes, and to optimize future clinical decisions.

Contribution of Multicenter Expertise and Deformable Fusion Software for Re-irradiations With Curative Intent

We propose to evaluate the contribution of a standardized process combining, * a validation of re-irradiation indications by a group of multi-professional experts (radiotherapists and physicists) and, * a collective validation of the accumulation of doses on all the organs of the anatomical region concerned obtained using deformable fusion software (MiM) allowing the accumulation of doses in terms of Equivalent Dose 2 Grays (EQD2). The primary objective of this study is to determine the rate of patients for whom this process has changed the treatment plan.

Radiotherapy of Multiple Brain Metastases Using AGuIX®

This is a Prospective Randomized Open Blinded Endpoint phase II clinical trial. The study will be adaptive: an interim analysis is planned after enrolment of 20 patients in each arm of treatment (WBRT and AGuIX® + WBRT), to select and continue the study with group(s) that present the best response rate to the experimental treatment (AGuIX® + WBRT). The main endpoint will be evaluated by a blinded endpoint committee.

Nimotuzumab Plus Radiotherapy in Elderly Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

This is a prospective, single-center, open-label, single-arm phase II study. The purpose of this study is to evaluate the efficacy and safety of nimotuzumab combined with concurrent intensity-modulated radiotherapy (IMRT) in elderly patients (≥65 years old) with locally advanced unresectable head-and-neck squamous cell carcinoma (HNSCC) who are unfit for standard concurrent cisplatin-based chemoradiotherapy. Eligible patients will receive standard-dose intensity-modulated radiotherapy together with weekly nimotuzumab. The primary endpoint is 1-year overall survival rate. Secondary endpoints include progression-free survival, objective tumor response rate, locoregional control rate, distant metastasis rate, and treatment-related adverse events. Patients will be followed up for survival, tumor status and safety assessments after treatment completion.

A Randomized Trial of Five Fraction Partial Breast Irradiation (RAPID2)

The primary objective of this study is to determine in women with node negative BC ≤3cm in size, if PBI compared to WBI, both given once-a-day over 1 week following BCS, is non-inferior for LR and reduces adverse cosmesis. The primary outcomes are LR and patient-assessed cosmesis at 3 years post randomization.