Establishment of Patient Derived Cancer Cell Models to Interrogate Novel Molecular Targets in Metastatic...
Metastatic CancerWith rapid advances in molecular oncology, the availability of preclinical in vitro cell models and in vivo animal models with specific genomic aberrations is critical for improved prediction of clinical outcomes in cancer patients. One of the most widely used preclinical models is conventional cell lines, such as the NCI-60 panel of cell lines;these cell lines are widely used in preclinical testing for novel targeted drugs, partially owing to the low expense and reduced labor associated with cell culture compared with other preclinical models, such as animal xenografts. However, recent studies have shown that accumulation of genetic aberrations in cancer cell lines occurs with increasing passage number. These models also lack the heterogeneity of tumors and do not exhibit a proper microenvironment, highlighting the limitations of cell-based models. Consistent with this, Johnson et al. demonstrated that in vivo activities of the cell lines within the NCI-60 panel did not closely correlate with corresponding human cancers. Therefore, to better preserve the genomic integrity and tumor heterogeneity observed in patients, patient-derived xenograft (PDX) models are being used more frequently. PDX is generated by directly transplanting freshly resected patient tumors into immunocompromised murine hosts with or without an intermediate in vitro culture step. This PDX model is an improvement over cell lines because it can provide both an appropriate tumor microenvironment and heterogeneity of tumor cells. However, the engraftment success rates and growth rates of implanted tumors are highly variable depending on the tumor type, possibly due to insufficient numbers of hematopoietic cells and/or ineffective microenvironmental cues in the mouse stroma. The extent to which tumor cells from freshly resected tumors are able to withstand mechanical stresses and xenotransplantation barriers is also unclear. Furthermore, the use of PDX models for application in clinical oncology is limited owing to the time required for PDX establishment (> 4 months) since most patients with refractory cancer live less than 1 year. Recently, PDC line models have been suggested as an alternative preclinical model to be used as a prediction tool for preclinical drug sensitivity. Therefore, in this study, the investigators aimed to overcome these potential barriers of pre-existing models by examining the capacity of PDC line models to recapitulate the histological and genomic features of primary patient tumors. In selected cases, the investigators screened drug sensitivity in vitro using PDC lines and compared the results with real-life clinical treatment outcomes.
Femoral Bone Metastases
CancerMetastatic Malignant Neoplasm to Femur1 moreBone is a common site of metastasis for a range of malignancies. Bone metastases have the potential to cause significant morbidity including pain, impairment of ambulation and reduced functional independence. Previous research has shown that pathological fractures are observed in 9 to 29 percent of patients with long bone metastases, and a high proportion of these require surgical intervention to relieve pain and restore function. The goal of this study is to describe the clinical outcomes of patients with femoral metastases at high risk of pathological fracture. Patients referred for treatment of femoral metastases at high risk of fracture will be followed prospectively after undergoing with surgery (± post-operative radiotherapy), or radiotherapy alone. Patient and disease characteristics, ambulatory status and limb function will be documented before treatment. These Clinical outcomes of participants in each treatment group will be measured 6 weeks after treatment, and 3- and 6 months after enrolment, with particular reference to patient-reported outcomes relating to pain, ambulatory status, limb function and quality of life.
SBRT of Metastases Following Neo-adjuvant Treatment for Colorectal Cancer With Synchronous Liver...
Colorectal CancerLiver Metastasis Colon CancerThe purpose of this study is to prospectively evaluate the feasibility of SBRT for the management of synchronous oligo metastatic liver metastases from colorectal cancers.
Recombinant Human Adenovirus Type 5 Injection Combined With PD-1 Monoclonal Antibody and Nab-paclitaxel...
Malignant MelanomaLiver MetastasesThis study is the first to explore the efficacy and safety of recombinant human adenovirus type 5 injection combined with PD-1 monoclonal antibody and nab-paclitaxel in the treatment of patients with liver metastases of melanoma, in order to provide a new method for the clinical treatment of melanoma. The model also provides reference and basis for other tumor treatments.
A Study of Oral IRAK-4 Inhibitor CA-4948 in Combination With Pembrolizumab Following Stereotactic...
Melanoma Metastatic in the BrainThis phase I/II trial will investigate the use of the novel oral IRAK-4 inhibitor CA-4948 in combination with pembrolizumab therapy following stereotactic radiosurgery in patients with melanoma brain metastases (MBM). The investigators hypothesize that the addition of CA-4948 will reduce the rate of distant intracranial failure and reduce the need for subsequent radiation therapy. The investigators also propose that it will have a significant reduction in radiation necrosis and improve patient-reported symptoms and quality of life. This trial represents the first time an oral IRAK-4 inhibitor has been used in combination with aPD1 therapy in MBM and will yield valuable insight into its synergistic potential both in MBM and additional sites of metastases.
Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab...
HCC - Hepatocellular CarcinomaMetastatic Cancer1 moreTRIPLET HCC is a phase II-III trial that assess the effectivness of addition of ipilimumab to the combination atezolizumab-bevacizumab, on global survival and response to the treatment, for patients with advanced or metastatic hepatocellular carcinoma. The theoretical duration of the study is 5 years. In the scope of this study, each patient will have 2 years of treatment and 2 years of follow-up from their enrollment date.
Efficacy and Safety of Apalutamide in Combination With 89Sr as Neoadjuvant Therapy in Prostate Cancer...
Prostate Cancer With ≤10 Bone MetastasesThe aim of this study is to evaluate the efficacy and safety of apalutamide in combination with 89Sr as neoadjuvant therapy in prostate cancer with ≤10 bone metastases. The primary endpoint is PFS and the second endpoints are pCR, rPFS, PSA response, pain score, number and extent of bone metastases.
Neoadjuvant vs. Intraoperative vs. Adjuvant Resection Cavity Radiotherapy of Brain Metastases
Brain MetastasesRadiotherapyPatients suffering from malignancies in advanced stages often develop brain metastases, which limit both the life span and the quality of life. Combining surgery and radiotherapy for resectable brain metastases is standard of care but there is a lot of controversy on which kind of radiotherapy is best suitable. Recently, first volumetric in-silico analyses point to theoretical advantages of neoadjuvant stereotactic radiotherapy of brain metastases. Special about this trial is the direct comparison between the three currently discussed radiotherapy options for resectable brain metastases: Neoadjuvant stereotactic radiotherapy, intraoperative radiotherapy and adjuvant stereotactic radiotherapy.
Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy...
Lung MetastasesColorectal Cancer MetastaticCOPPER is an international, multicenter, parallel-arm, phase III randomized controlled trial comparing two local treatment strategies (SABR or metastasectomy) for patients with an indication for local treatment for limited (max. three) colorectal pulmonary metastases
HER3-DXd in Breast Cancer and NSCLC Brain Metastases and Solid Tumor Leptomeningeal Disease
Metastatic Breast CancerAdvanced Non-Small Cell Squamous Lung Cancer2 moreThe goal of this phase II clinical trial] is to analyze the efficacy of patritumab deruxtecan (HER3-DXd) in patients with metastatic breast cancer (MBC) or advanced non-small cell lung cancer (aNSCLC) with active brain metastases (BM) who have received at least one line of systemic therapy in the advanced setting, or patients with active leptomeningeal carcinomatosis/disease (LMD) after radiotherapy from an advanced solid tumor who do not need immediate local treatment, and have not received prior treatment with an anti-HER3 targeted drug]. The main questions it aims to answer are: The intracranial objective response rate (ORR-IC) per local investigator as judged by best central nervous system (CNS) response according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria of HER3-DXd in patients with active BM from MBC (Cohort 1) and aNSCLC (Cohort 2). The overall survival (OS) rate at 3 months of HER3-DXd in patients with advanced solid tumors with untreated LMD (Cohort 3). Participants will receive HER3-DXd on day (D1) of each 21-day cycle until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Researchers will compare historical groups to see if HER3-DXd positively impacts patient outcomes.