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NCT ID: NCT05131698 Active, not recruiting - Lenvatinib Clinical Trials

Clinical Study of the Efficacy and Safety of Transhepatic Arterial Chemoembolization Combined With Tislelizumab and Lenvatinib in Patients With Advanced Unresectable Hepatocellular Carcinoma

Start date: March 1, 2021
Phase: Early Phase 1
Study type: Interventional

ICIs combined with AATDs have gradually become the mainstream treatment modality for advanced hepatocellular carcinoma, and more related clinical trials are underway. This is undoubtedly a breakthrough and the main direction for improving the overall 5-year survival rate of the liver cancer population in the next decade, and a touchstone for exploring the development and value of liver surgery in the era of comprehensive treatment for advanced hepatocellular carcinoma. Overall, there are relatively few reports on various types of translational therapy for advanced HCC, probably for the following two reasons: (1) advanced hepatocellular carcinoma is complex, rapidly progressing, difficult to treat, and has low translational efficiency; (2) the existing translational therapy strategies are highly selective in terms of applicable population, complex treatment process, and institutional dependence, and cannot achieve efficient and successful translation. At present, there are few studies reported on the application of TACE+ICIs+AATDs to carry out translational therapy. In the absence of relevant guidelines for reference, advanced hepatocellular carcinoma may be the best entrance to carry out translational therapy with ICIs combined with AATDs, and after satisfactory results are achieved in the treatment of this group of patients, a point-to-point effect can be generated, facilitating the transformation of TACE+ICIs+AATDs The target population of TACE+ICIs+AATDs translational therapy can be further expanded. To promote the development of hepatocellular carcinoma treatment and improve the long-term survival rate of the overall hepatocellular carcinoma population. In this study, we enrolled patients with advanced HCC and used TACE+ICIs+AATDs for conversion therapy to improve the conversion rate, so that unresectable HCC patients could be converted to a chronic disease state and achieve long-term survival on the one hand, and provide potential for sequential surgical treatment on the other. The drug of choice is lenvatinib. This study provides a basis for the clinical application of translational therapy for advanced hepatocellular carcinoma.

NCT ID: NCT05127590 Active, not recruiting - Clinical trials for Advanced Squamous Non-Small Cell Lung Carcinoma

RBN-2397 in Combination With Pembrolizumab in Patients With SCCL

Start date: March 15, 2022
Phase: Phase 1/Phase 2
Study type: Interventional

RBN-2397 inhibits PARP7, an enzyme that is switched on by cancer stresses, such as the toxins in cigarette smoke. Cancer cells use PARP7 to hide from the immune system by stopping the cell from sending a signal (Type 1 interferon) that tells the immune system that something is wrong and to kill the cell. RBN-2397 has been shown in animal and human studies to inhibit tumor growth and also shuts down the "don't kill me" signal the tumor is sending to evade the immune system. The purpose of this study is to determine if RBN-2397 in combination with pembrolizumab (a PD-1 inhibitor) has the ability to restore the response to treatment in patients with SCCL that have been previously treated with a PD-1/PD-1 ligand (PD-L1) inhibitor and have had a response followed by disease progression. The Phase 1b portion of the study will assess the safety of RBN-2397 in combination with pembrolizumab (a PD-1 inhibitor) and define the dose of RBN-2397 to be used in combination with pembrolizumab for the Phase 2. The Phase 2 portion of the study will assess the anti-tumor activity of RBN-2397 in combination with pembrolizumab.

NCT ID: NCT05122546 Active, not recruiting - Clinical trials for Metastatic Renal Cell Carcinoma

CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer

Start date: November 1, 2021
Phase: Phase 1
Study type: Interventional

This phase I trial evaluates the effects of CBM588 in combination with standard therapies, nivolumab and cabozantinib, in treating patients with kidney cancer that has spread to other places in the body (advanced/metastatic). The digestive microbiome may have an effect on how patients respond to treatment, and previous research shows that a specific bacteria found in the gut (Bifidobacterium) may predispose participants to a better response to standard therapies. CBM588 is a strain of bacteria that can restore species of Bifidobacterium to the microbiome. The primary aim of this study is to determine how CBM588 changes the microbiome of patients with metastatic renal cell carcinoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving CBM588, nivolumab, and cabozantinib may kill more tumor cells.

NCT ID: NCT05113290 Active, not recruiting - Clinical trials for Hepatocellular Carcinoma

Effect and Safety of Recombinant Human Adenovirus Type 5 in Advanced HCC With Stable Disease After Sorafenib Treatment

Start date: December 28, 2021
Phase: Phase 4
Study type: Interventional

Sorafenib, as a first-line treatment for patients with advanced HCC, can significantly prolong the overall survival rate of patients. However, about 53-71% of patients showed stable disease (SD) after sorafenib treatment, and further studies to explore optimal therapy for these patients are still needed. Oncolytic viruses are a type of virus that can selectively replicate in tumor cells and then destroy tumor cells, of which recombinant human adenovirus type 5 (H101) is the first oncolytic virus drug which was approved in the world. Recent studies indicate that H101 shows anti-tumor effects on liver cancer and there may be a synergistic effect between recombinant human adenovirus type 5 and sorafenib in the inhabitation of hepatoma cells in vitro. This study aims to further verify the effect and safety of recombinant human adenovirus type 5 combined with sorafenib in the treatment of advanced hepatocellular carcinoma.

NCT ID: NCT05113186 Active, not recruiting - Clinical trials for Hepatocellular Carcinoma

Neoadjuvant and Adjuvant Lenvatinib in HCC Patients Treated by Percutaneous Ablative

LENVABLA
Start date: February 2, 2022
Phase: Phase 2
Study type: Interventional

Percutaneous ablation (PA) is the only non-surgical curative treatment of hepatocellular carcinoma (HCC). Due to its excellent tolerance, particularly in patients with portal hypertension or bearing comorbidities, it now represents in France nearly 70% of the first-line curative treatment of "in Milan" tumours. For HCC less than 3 cm, ideal indication for percutaneous ablations, results of monopolar radiofrequency ablation (mRFA), are excellent with only 5% of reported non-tumoral control after a first procedure. In addition to mRFA the arsenal of ablations has grown considerably with the emergence of new techniques which allow the expansion of indications for PA, especially in patients with poor prognostic tumors or relatively advanced beyond the Milan criteria. In this setting, multibipolar mode using no touch technique (mbpRFAnt) increases the tumour volume than can be ablated, allowing the removal of large tumors> 5 cm. Inadequate tumour control is then de facto greater in these situations, around 20%. Difficult-to-access tumors can furthermore be treated by percutaneous irreversible electrotroporation (IRE). Despite a tumor burden accessible for curative ablation, a phenotype of "aggressive" HCC characterized by high rates of local recurrences is yet to be defined. Up to now, several characteristics might define this subtype with a poor-prognosis and include 1) high serum alpha-foetoprotein (AFP) levels, 2) radiological infiltrative form, and 3) histological macrotrabecular subtype. Based on these characteristics, median recurrence-free survival of these patients is usually below 10 months. High serum AFP level is a well-known predictor of HCC recurrence following curative procedure. In patients treated by percutaneous ablation, regardless of the technique used and irrespective of tumor burden, high baseline serum AFP level has tenaciously been reported as an independent predictor or recurrence.. More recently, the radiological description of infiltrative HCC (as opposed to mass-forming) has been identified as an aggressive from of HCC with a poor prognosis even when eligible for ablation. This aspect is often associated with infra-clinical invasion of the portal veins (PV), leading to poor prognosis. Finally, a "massive macrotrabecular" (MTM) histological subtype of HCC associated with specific molecular features has recently been described. This MTM-HCC subtype, reliably observed in 12% of patients eligible for curative treatment, represents an aggressive form of HCC is an independent predictor of early and overall recurrence following PA, which is retained even after patient stratification according to common clinical, biological, and pathological features of aggressiveness. The idea of optimizing HCC curative treatments using adjuvant biotherapy, particularly in patients with poor-prognosis tumors in curative intent, is particularly attractive. One trial in adjuvant setting was conducted, the STORM trial, that tested the benefit of sorafenib in curative intent of in Milan HCC. This negative trial included patients within Milan HCC, with an expected low rate of recurrence with only few patients treated by PA. Lenvatinib is a multikinase inhibitor which has been recently approved as firs-line therapy for advanced HCC. The investigators assume that lenvatinib could have also a synergistic local action with PA in two ways. First, given as neoadjuvant regimen, lenvatinib by reducing tumor and liver perfusion could decrease the global heat sink effect associated with loco-regional blood microcirculation during PA. Second, by carrying on in adjuvant treatment, lenvatinib could decrease the magnitude of non-specific inflammatory angiogenesis around the treatment zone, therefore reducing the risk of locoregional (intrasegmental) cells tumor spreading or promotion. Given the dismall prognosis of the aforementioned poor-prognosis HCC eligible for PA with an overall median recurrence-free survival below 10 months, the investigators hypothesis is that addition of Lenvatinib as neo- and adjuvant therapy might increase tumour control in these difficult-to-treat patients. Patients combining either high serum AFP levels, infiltrative form or MTM-HCC histological subtype represent 30% of BCLC A stage HCC patients in expert centers, and are the ideal candidates for such trials. Therefore, the first aim of this proposal is to assess the benefit of lenvatinib in neo- and adjuvant setting combined with curative percutaneous ablation for BCLC A HCC patients considered at high risk of local recurrence (high AFP or infiltrative form or macrotrabecular massive subtype).

NCT ID: NCT05112510 Active, not recruiting - Clinical trials for Patients With Nasopharyngeal Carcinoma

Prognostic Prediction of NPC Based on MR Diffusion-weighted Imaging

Start date: June 1, 2021
Phase:
Study type: Observational

The purpose of this study is to explore whether the imaging model based on RESOLVE-DWI sequence can exploiting the heterogeneity of nasopharyngeal carcinoma and indicate the prognosis, so as to provide intervention information for clinical decision-making. All patients were randomly divided into the training group and the validation group. Radiomics features extracted from T2-weighted, DWI, apparent diffusion coefficient (ADC), and contrast- enhanced T1-weighted were used to build a radiomics model. Patients'clinical variables were also obtained to build a clinical model. Model of training cohort was established using cross-validation for nasopharyngeal carcinoma prognosis by machine learning, including Logistics Regression, SVM, KNN, Decision Tree, Random Forest, XGBoost, and then, the model will be verified in the validation cohort. Area under the curve (AUC) of the Machine learning model was used as the main evaluation metric.

NCT ID: NCT05104567 Active, not recruiting - Colorectal Cancer Clinical Trials

A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)

Start date: December 9, 2021
Phase: Phase 2
Study type: Interventional

The study is a phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with other anticancer therapies for the treatment of participants aged 18 years and older with advanced and metastatic gastrointestinal cancer. This study is structured as a master protocol for the investigation of SAR444245 with other anticancer therapies. Sub study 01 - Cohort A aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC). Sub study 02 - Cohort B1, B2 and B3 would focus on non MSI-H tumors with a large unmet need to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), especially with low PD-L1 expression or after progression on prior PD1/PD-L1-based regimens. Sub study 03 - Cohort C aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in participants with advanced unresectable or metastatic HCC who relapsed on prior PD1/PD-L1-based regimens. Sub study 04 - Cohort D1 and D2 aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with either the anti-PD1 antibody pembrolizumab or with the anti-EGFR IgG1 antibody cetuximab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic colorectal cancer (mCRC).

NCT ID: NCT05101629 Active, not recruiting - Clinical trials for Hepatocellular Carcinoma

Pembrolizumab and Lenvatinib in Patients With Advanced HCC Who Are Refractory to Atezolizumab and Bevacizumab/ IO-based Therapy

Start date: May 11, 2022
Phase: Phase 2
Study type: Interventional

Patients with advanced HCC, refractory to atezolizumab and bevacizumab /IO-based therapy will be treated with pembrolizumab and lenvatinib. Efficacy of the combination therapy will be assessed by objective reponse rate, progression free survival, overal survival, safety/tolerability.

NCT ID: NCT05099848 Active, not recruiting - Clinical trials for Hepatocellular Carcinoma

A Trial of Conversion Treatment of HAIC Combined With Camrelizumab and Apatinib for Unresected Hepatocellular Carcinoma

Start date: March 17, 2021
Phase: Phase 2
Study type: Interventional

The study is being conducted to evaluate the efficacy and safety of conversion treatment of Hepatic Arterial Infusion Chemotherapy combined with Camrelizumab and Apatinib for unresected hepatocellular carcinoma.

NCT ID: NCT05096663 Active, not recruiting - Clinical trials for Stage IV Lung Cancer AJCC v8

Testing the Use of Combination Immunotherapy Treatment (N-803 [ALT-803] Plus Pembrolizumab) Against the Usual Treatment for Advanced Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)

Start date: March 15, 2022
Phase: Phase 2/Phase 3
Study type: Interventional

This phase II/III Lung-MAP trial studies how well immunotherapy treatment with N-803 (ALT-803) and pembrolizumab working in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). Natural killer cells, part of our immune system, are always on alert and ready to defend our bodies from many kinds of infection or rogue cells, such as those that cause cancer. N-803 (ALT-803) may activate natural killer cells so that they can stimulate an immune response to help fight cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving N-803 (ALT-803) and pembrolizumab may help shrink and stabilize lung cancer or prevent it from returning.