Clinical Research Directory

Partial Immune-boost TACE in unrEseCTable HCC Patients Under Systemic Treatment

Study Objectives： Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) combined with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) or Durvalumab (anti-programmed death-ligand 1; anti-PD-L1) combined with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4; anti-CTLA4) have recently been established as a standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). However, its objective response rate (ORR) is only less than 27% (1, 2), and the majority of patients died of HCC progression and liver failure. Therefore, there is an urgent need to develop a novel combination treatment strategy to overcome resistance to immunotherapy and improve patient outcomes. Transarterial chemoembolization (TACE) remains the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) (3, 4). However, in our previous retrospective study (5-7), the investigators consistently observed that this combination not only improves therapeutic responses but also significantly prolongs patient survival. The tumor necrosis caused by TACE may enhance the efficacy of systemic therapies by promoting the release of neoantigens, thereby stimulating immune responses (8-14). This concept has been substantiated in two recent trials involving intermediate-stage HCC (15, 16), where the addition of immune checkpoint inhibitors to TACE resulted in improved clinical outcomes. Nevertheless, this promising approach has yet to replace the decades-old standard treatment protocols, underscoring the need for further proof-of-concept studies. Both immunotherapy (atezolizumab/bevacizumab or durvalumab/tremelimumab) and transarterial chemoembolization (TACE) are approved treatment modalities for unresectable hepatocellular carcinoma (HCC) by the U.S. and Taiwan Food and Drug Administration (FDA). This phase II non-randomized trial is designed to prospectively evaluate the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with a combination of immunotherapy and TACE. A particular focus of this study is to explore the potential immune-boosting effects of TACE, including its ability to enhance antigen presentation and stimulate anti-tumor immune responses.

Adebrelimab ±Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Unresectable Locally Advanced ESCC

To evaluate the efficacy and safety of adebrelimab with or without induction chemotherapy followed by concurrent chemoradiotherapy for unresectable locally advanced esophageal squamous cell carcinoma

MRD-Guided Postoperative Surveillance and Adaptive Treatment for Resectable Lung Cancer

This study is a prospective single-arm clinical trial targeting patients with stage IB-IIIA non-small cell lung cancer (NSCLC) who have received neoadjuvant immunotherapy. The primary objective is to evaluate whether a personalized follow-up and adjuvant treatment strategy-based on the combination of ctDNA-based minimal residual disease (MRD) testing and pathological response-can effectively improve the 2-year postoperative recurrence-free survival (RFS). The study will enroll 100 patients scheduled for radical surgery who have undergone neoadjuvant immunotherapy (in combination with platinum-based chemotherapy). Patients will receive individualized follow-up and adjuvant therapy based on dynamic changes in ctDNA at various preoperative and postoperative timepoints, as well as pathological response. Adjuvant therapy will be recommended if patients do not achieve pathological complete response (pCR) after surgery, or if ctDNA testing is positive after neoadjuvant therapy or post-surgery. Only patients who achieve pCR and have negative ctDNA at both specified timepoints will forgo adjuvant therapy; these patients will undergo blood sampling at each routine follow-up, with adjuvant therapy initiated upon ctDNA seroconversion to positive. The primary endpoint is 2-year RFS after surgery; secondary endpoints include overall survival (OS) and the diagnostic rate of recurrence/metastasis based on ctDNA-MRD testing. This project aims to explore the refinement of adaptive treatment strategies in the neoadjuvant immunotherapy lung cancer population, with the ultimate goal of improving overall therapeutic efficacy and establishing a standardized, integrated postoperative management system suitable for lung cancer patients.

Antibody-Drug Conjugate Plus Immunotherapy Versus Immunotherapy Plus Chemotherapy for Extensive Transurethrally Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer

This randomized controlled trial aims to evaluate the efficacy and safety of antibody-drug conjugate (ADC) plus immunotherapy compared with immunotherapy plus chemotherapy in patients with extensive transurethrally unresectable very-high-risk non-muscle-invasive bladder cancer (NMIBC). Patients will be randomly assigned to receive either ADC plus immunotherapy or immunotherapy plus chemotherapy. The study will assess the effectiveness of these two treatment strategies in achieving complete response, maintaining disease control, and preserving the bladder, as well as their safety and tolerability. The findings may help identify an effective bladder-preserving treatment strategy for patients with extensive very-high-risk NMIBC who cannot undergo complete transurethral resection.

Effects of Supervised Aerobic Exercise on Biomarkers in Patients With nSCLC Receiving Immunotherapy

Exercise is increasingly recognized as a supportive intervention in oncology and may influence systemic inflammation, immune regulation, physical function, and the tumor microenvironment among patients with non-small cell lung cancer. The EXIMPACT trial will investigate the effects of a supervised aerobic exercise program on immune system- and tumor microenvironment-related biomarkers in patients with NSCLC receiving active immunotherapy. Although immunotherapy has improved outcomes for patients with NSCLC, factors influencing treatment response and strategies to enhance treatment efficacy remain under investigation.

PULSAR Radiotherapy Combined With Immunotherapy for High-Risk Advanced Liver Cancer

The goal of this clinical trial is to learn if adding PULSAR, a personalized adaptive stereotactic radiotherapy, to standard immunotherapy can control cancer longer in adults with high-risk advanced hepatocellular carcinoma (liver cancer). It will also learn about the safety of this combination. The main questions it aims to answer are: * What percentage of participants are alive without cancer progression 12 months after starting PULSAR? * What medical problems do participants have after PULSAR with immunotherapy? There is no comparison group. Results will be compared with published results of immunotherapy alone. Participants will: * Continue their usual immunotherapy * Receive 2 to 3 PULSAR sessions, 3 to 4 weeks apart, with the plan adjusted before each session * Give blood samples and fill out symptom questionnaires * Have checkups and scans for up to 3 years

Thymalfasin Combined With Chemotherapy and Immunotherapy in TNBC Neoadjuvant Treatment

This is a prospective, open-label, single-center, phase II, randomized controlled clinical trial involving patients with triple-negative breast cancer who meet the criteria for neoadjuvant chemotherapy (T \> 2 cm, N+). The study aims to further validate the sensitizing effect and safety of Thymalfasin in combination with neoadjuvant chemotherapy and immunotherapy by comparing the 3-year event-free survival (EFS) and IFNγ elevation rates between the group receiving Thymalfasin in combinatione with standard neoadjuvant chemotherapy and immunotherapy and the control group receiving standard neoadjuvant chemotherapy and immunotherapy alone.

A Clinical Study on Neoadjuvant Treatment of Resectable Head and Neck Squamous Carcinoma With Immune-targeted Therapy and Lysogenic HSV Virus

Evaluation of the safety and tolerability of immune-targeted therapy combined with neoadjuvant therapy with lysogenic HSV virus for patients with surgically resectable squamous carcinoma of the head and neck.

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.

Tumor Microenvironment in Gastric Cancer Patients Treated With Combined Immunotherapy and Chemotherapy

The goal of this study is to analyze the tumor microenvironment (TME) in gastric cancer patients treated with combined immunotherapy and chemotherapy. The main questions it aims to answer are: * Provide profiles of TME between pre-treatment and post-treatment to gain insights into the mechanisms of immunotherapy combined with chemotherapy in advanced gastric cancer * Investigate the crucial factors affecting treatment efficacy by comparing gastric cancer patients with varying treatment responses

FAPI-Guided Radiotherapy With Cadonilimab and Standard Chemotherapy for Colorectal Peritoneal Metastasis: A Phase III Randomized Controlled Trial (TORHC-PM02)

The goal of this clinical trial is to test whether adding targeted radiation plus cadonilimab immunotherapy to standard second-line chemo works better for adults with colorectal cancer only spread to the peritoneum, and check how safe this combined treatment is. Its main research questions are: Does the combined treatment slow cancer growth for a longer time than standard chemo alone? What side effects will participants get from the new combination therapy? Researchers will compare the chemo-radiation-immunotherapy combination against standard chemo alone to see if the new plan shrinks tumors and improves outcomes. Participants will: Receive either the new combined treatment or standard chemo chosen randomly by chance Visit the hospital regularly for drug infusions, scans and physical exams Complete questionnaires about daily quality of life and report any discomfort

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.

RADICAL-IO: thRee Cycles of immunotherApy Without raDical Therapy In mediCALly InOperable Stage I Non-small Cell Lung Cancer

Traditionally, chemotherapy and/or immunotherapy are combined with surgery or radiotherapy to cure patients with lung cancer. However, some patients treated with immunotherapy appear to be cured before surgery or radiotherapy. In this study, patients with a high chance to respond to immunotherapy will be selected. These patients will be treated with immunotherapy alone, thereby evaluating whether these patients can be cured without surgery or radiotherapy.

Jack Jumper Ant Venom Immunotherapy Long-term Effectiveness Investigation

Jack Jumper ant (JJA) venom allergy is a uniquely Australian medical condition. It is the leading cause of venom allergy and affects up to three per cent of the population. 70 percent of people with JJA allergy will have another reaction on a repeat sting and this sensitivity appears to persist for many years. Venom immunotherapy (VIT) has been shown to be a safe and effective treatment in the prevention of severe systemic allergic reactions (anaphylaxis) to future stings. It is currently offered to patients as standard care in Tasmania, South Australia and Victoria. However, whilst JJA VIT has been used for many years, there is a lack of evidence on the long-term benefit of the treatment and how it impacts patient quality of life. This trial will offer patients who have completed a JJA VIT program (between 3 and \< 6-years duration) and have been off-treatment for at least 18-months and \< 5 years, to have a supervised JJA sting challenge and blood test to assess their JJA venom tolerance level. It will also ask them to complete a set of questionnaires at different timepoints to obtain a history of their exposure and reactions to JJA stings outside of the hospital setting (field stings), and to measure the impact of the completed VIT and knowledge of their sting challenge outcome on their quality of life and their behaviours around auto-injectors. These measures will be used to explore the long-term effectiveness of JJA VIT and the impact of a sting challenge post VIT on a patient's quality of life.

The Efficacy and Safety of Narlumosbart in Combination With Stereotactic Body Radiation Therapy to Improve the Efficacy of First-line Chemotherapy Combined With Immunotherapy in Patients With Bone Metastases From Advanced Non-small Cell Lung Cancer

Introduction: Immunotherapy in combination with chemotherapy have been recommended as the first-line treatment of driver-negative advanced non-small cell lung cancer (NSCLC), but the efficacy is worse in NSCLC patients with bone metastases due to the immunosuppressive microenvironment. Studies have shown that not only the nuclear factor kappa-B ligand (RANKL) inhibitors but also Stereotactic Body Radiation Therapy (SBRT) play a significant role in improving the tumor immune microenvironment. Therefore, narlumosbart，a monoclonal antibody (mAb) targeting RANKL，in combination with SBRT may have synergistic effects and improve efficacy of immunotherapy and chemotherapy in driver-negative advanced NSCLC patients with bone metastases. Methods: This single-arm, single-center phase II clinical trial will enroll NSCLC patients with bone metastases who have not received any systemic therapy. Patients will receive narlumosbart and bone target lesion SBRT in combination with first-line treatment immunotherapy and chemotherapy after screening eligible subjects. Narlumosbart, 120mg/time, subcutaneous injection, will be administered every 4 weeks. For the treatment of SBRT for bone metastases, the dose of 24Gy/3F is used for spinal metastases, and 30Gy/5F or 35Gy/5F is used for non-spinal lesions. Chemotherapy combined with immune checkpoint inhibitor therapy will be used in accordance with the guidelines. The primary endpoint is to assess the objective response rate of NSCLC patients with bone metastases from narlumosbart combined with SBRT and first-line chemotherapy and immunotherapy. The secondary endpoints include safety and tolerability, progression-free survival, overall survival, bone-related events, pain score, and quality of life. Sample size was calculated using the Simon's Two-Stage method. 9 patients will be enrolled in the first stage. If ≥ 2 patients achieve CR/PR, the second stage of enrollment will be performed. If fewer than 2 patients achieve CR/PR, the trial will be terminated. In the second phase, 15 patients will be enrolled. 27 subjects will be enrolled in this project, considering the dropout rate of 10%. Wangjun Yan AND Zhengfei Zhu are the Co-Principal Investigators of this study.

Application of MRI Radiomics Features in Neoadjuvant Therapy of Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma is the sixth most common malignant tumor in the world. Neoadjuvant therapy, including neoadjuvant chemotherapy and immunotherapy, is recommended for patients with locally advanced head and neck cancer. The response to neoadjuvant therapy varies among the patients. It is reported that about 37% of the patients achieve pathological complete response after receiving neoadjuvant therapy, who would achieve a better prognosis compared with the patients with non-pathological complete response. It is significant to predict and assess response to neoadjuvant therapy for the patients with head and neck cancer accurately, which could assist in formulating individualized therapeutic regimens. MRI has good soft tissue resolution and is a common preoperative examination method. However, this method lacks the ability to accurately predict the probability of patients achieving pathological remission after neoadjuvant therapy. At present, it is a novel and effective method to construct a model to predict the efficacy of neoadjuvant therapy based on MRI image omics analysis, and certain achievements have been made in breast cancer and rectal cancer. In this study, multi-sequence MRI was combined with clinical risk factors to construct an imaging omics model to predict the probability of pathological complete remission of patients with head and neck squamous cell carcinoma after neoadjuvant therapy, and to accurately identify diagnostic imaging remission, so as to better assist clinical decision-making.

Improving Patient and Caregiver Understanding of Risks and Benefits of Immunotherapy for Advanced Cancer

The purpose of this study is to refine and pilot test educational material developed to educate and support patients receiving immunotherapy for advanced cancer. The intervention is an educational video and question prompt list (QPL) to promote communication between patients, caregivers, and the oncology team about the risks and benefits of immunotherapy.

Safety and Efficacy Study of Sorbitol With Neoadjuvant Chemotherapy Combined With Tirellizumab (PD-1 Inhibitor) in Patients With Locally Advanced Gastric Cancer

The goal of this clinical trial is to learn if sorbitol works to enhance the therapeutic effect of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. It will also learn about the safety of sorbitol. The main questions it aims to answer are: Does sorbitol enhance the therapeutic effect of immunotherapy and increase the major response rate in patients with locally advanced gastric cancer? Does sorbitol with neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) can improve the prognosis of patients with locally advanced gastric cancer? Researchers will compare sorbitol to a standard-of-care treatment (aPD-1 + SOX chemotherapy) to see if sorbitol works to enhance the therapeutic effect (Add-on Effect) of neoadjuvant chemotherapy combined with Tirellizumab (PD-1 inhibitor) in patients with locally advanced gastric cancer. Participants will: Take sorbitol every day for 3 months in 3 treatment cycles Visit the clinic once every 4 weeks for checkups and tests Keep a diary of their symptoms and the number of times they use a rescue inhaler Participants will follow up as planned until PD occurs, informed consent is withdrawn, or follow-up is lost (whichever occurs first). After the end of treatment and safety follow-up, all subjects will be followed up for survival (OS data collected every 3 months ±14 days).

Short-Course Radiotherapy Followed by CAPOX With or Without Iparomlimab and Tuvonralimab in pMMR/MSS Locally Advanced Rectal Cancer

This multicenter, randomized, controlled, phase III trial evaluates whether adding iparomlimab and tuvonralimab injection to CAPOX consolidation chemotherapy after short-course radiotherapy improves tumor response in patients with treatment-naive, proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced rectal adenocarcinoma. Eligible patients will be randomly assigned in a 1:1 ratio to receive short-course radiotherapy followed by CAPOX plus iparomlimab and tuvonralimab, or short-course radiotherapy followed by CAPOX alone. After total neoadjuvant therapy, patients with a clinical complete response may undergo a Watch-and-Wait strategy, whereas other patients will undergo total mesorectal excision according to standard clinical practice. The primary endpoint is complete response rate, defined as pathologic complete response after surgery or clinical complete response sustained for more than 1 year. Secondary endpoints include 3-year relapse-free survival, 3-year overall survival, sphincter preservation rate, and grade 3-4 acute adverse events. Exploratory analyses will assess tissue and blood biomarkers associated with treatment response.

Assessment of Adebelizumab Combined With Chemotherapy in Concurrent Radiotherapy Versus Sequential Radiotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer

Immunotherapy combined with chemotherapy has emerged as the standard of care for patients with extensive-stage small cell lung cancer (ES-SCLC). The incorporation of thoracic radiotherapy can enhance treatment efficacy. Currently, the main types of research investigating immunotherapy combined with thoracic radiotherapy for untreated ES-SCLC are concurrent radiotherapy and sequential radiotherapy. The aim of this study is to evaluate the efficacy of adebelizumab in combination with chemotherapy, when administered concurrently with radiotherapy versus sequentially with radiotherapy, as a first-line treatment for ES-SCLC.

Study of Neoadjuvant Cemiplimab and Dupilumab in Early-Stage Non-Small Cell Lung Cancer

This phase 1b/2a study evaluates the safety, feasibility, and efficacy of combining dupilumab (anti-IL-4Rα) and cemiplimab (anti-PD-1) in patients with early-stage, resectable NSCLC. Phase 1b focuses on safety and feasibility, using a 3+3 design to monitor dose-limiting toxicities (DLTs), while Phase 2a assesses the major pathological response (MPR) rate with a Simon's two-stage minimax design. Secondary endpoints include event-free survival, overall survival, and translational objectives such as deep immune monitoring from patient samples, with the trial expected to enroll 24 patients at CHUM over five years.

Surgery After Verifying Existing Disease in Locally Advanced Operable Lung Cancer: A Pilot Study

The SAVED LUNG study is a pilot Phase I trial evaluating safety and feasibility of observation versus standard-of-care surgery in operable Stage II-III (excluding N3) NSCLC patients (PD-L1 ≥50%) who achieve complete clinical response following neoadjuvant platinum-doublet chemotherapy and immunotherapy. Participants are randomized to observation or surgery after rigorous restaging, with primary endpoints focusing on safety and feasibility. Secondary objectives include rates of cross-over to surgery, event-free survival, and overall survival, while exploratory endpoints examine ctDNA clearance and its association with clinical response.

Investigating Real-Time Immunotherapy Symptoms Study

The goal of this study is to evaluate the feasibility of using information from wearable devices and self-reported symptoms to remotely monitor patients during immunotherapy. The main questions it aims to answer are: * Is the digital remote patient monitoring tool feasible and acceptable to patients? * Do the alerts and guidance improve symptom management, quality of life, and engagement with the care team during treatment? Participants will: * Complete a demographic questionnaire at the beginning of the study and quality-of-life and health questionnaires at the beginning, midpoint, and end of study. * As feasible: At the beginning and end of the study, complete an in-person physical function assessment measuring balance (Short Physical Performance Battery). If participant is randomly assigned to the intervention group, they will also: * Complete weekly symptom ratings via digital remote patient monitoring tool * Wear a Fitbit activity tracker as feasible for 90 days. * At the end of the study, complete a semi-structured interview to provide feedback on the study.

Developing and Testing the Effectiveness of Smart Healthcare Assisted Individualized Symptom Management Education and Home-based Exercise on Frailty, Treatment-related Adverse Events and Quality of Life in Advanced Gastric Cancer Patients Receiving Immunotherapy

The goal of this randomized controlled intervention is to develop and evaluate the effectiveness of the nurse-led with AI chatbot Individualized Symptom Management Education and Home-based Exercise (AI-ISME\&HE) based on The Theory of Symptom Self-Management (TSSM) on frailty, self-efficacy in cancer care, trAE, and quality of life in advanced gastric cancer patients receiving immunotherapy. The main questions it aims to answer are: * Can AI-ISME\&HE reduces frailty in advanced gastric cancer patients receiving immunotherapy? * Can AI-ISME\&HE increases quality of life in advanced gastric cancer patients receiving immunotherapy? * Can AI-ISME\&HE increases self-efficacy in advanced gastric cancer patients receiving immunotherapy? * Can AI-ISME\&HE reduces all-caused death in advanced gastric cancer patients receiving immunotherapy within two years? Researchers will compare usual routine care to see if AI-ISME\&HE can reduce frailty, all-caused death and increase quality of life and self-efficacy. Participants will not be blinded, but the outcome evaluator will be blinded. The participants will be asked to complete three tasks for 12 weeks: * Self-reporting treatment-related adverse events * Interacting with AI-ISME\&HE for seeking information related to self-management educational materials, including symptom management with the most reported trAEs and prevention from frailty * ViviFrail-based exercise