View clinical trials related to Metastatic Colorectal Cancer.
Filter by:Colorectal cancer (CRC) is the 3rd most common cancer worldwide and accounts for ~14,000 new diagnoses and ~5,000 deaths in the Netherlands yearly (1.9 million and 935 thousand on a global level). Large scale transcriptional profiling of primary CRC tumors has revealed the presence of four distinct consensus molecular subtypes (CMSs). The CMS4 subtype is associated with a poor prognosis, especially in early CRC, and may benefit less from several standard systemic treatments (e.g. oxaliplatin, 5-fluorouracil, cetuximab), while being relatively sensitive to irinotecan. This is relevant as in the metastatic setting often the first choice first-line systemic therapy regimen is oxaliplatin and not irinotecan-based. Furthermore, tumor cells can acquire a CMS4 phenotype following exposure to chemotherapy, which may contribute to therapy resistance. CMS4 accounts for ~25% of all early-stage CRC patients and is more prevalent in advanced disease stages (~40% in stage IV CRC). Currently available CMS4 diagnostic tests require tumor tissue samples. The interpretation of biopsy-based CMS4 diagnosis is however complicated by large intra- and inter-lesion heterogeneity of CMS4 status. Extensive biopsy protocols could address the problem of CMS4 heterogeneity but are challenging in routine clinical practice. The development of CMS4-targeted therapy strategies therefore requires a more robust and clinically applicable diagnostic test for comprehensive quantitative assessment of CMS4 status of all lesions - primary and metastatic - in individual cancer patients. A promising solution for such a diagnostic test is to use a radiotracer that enables the quantitative assessment of CMS4 in vivo by whole body molecular imaging. This technique is particularly suited to assess biomarkers with heterogeneous expression: for diagnostic purposes, as a companion diagnostic for (targeted) therapies, or as part of a 'theranostic' strategy where patient selection using the diagnostic radiotracer is followed by treatment with the same tracer labeled to a therapeutic compound. Radiolabeled fibroblast activating protein inhibitor (FAPI) is an emerging diagnostic radiotracer that allows the comprehensive whole-body, whole-tumor assessment of fibroblast activation protein (FAP) expression in humans with a very low background uptake also at frequent CRC metastatic sites including the liver. FAP is an excellent candidate molecular imaging target for CMS4, as it is highly expressed on cancer-associated fibroblasts (CAF) that are abundantly present in this CRC subtype. Indeed, the investigators found that FAP gene-expression measured in tumor biopsies - as a single marker - accurately discriminates CMS4 from other CRC subtypes (area under the receiver operating characteristic curve (AUROC): 0.91; 95% confidence interval (CI): 0.90-0.93). The FoCus study will aim to take a next step by relating in vivo assessed FAP protein-expression by [18F]-ALF-FAPI-74 positron emission tomography (PET) / computed tomography (CT) to CMS4 status in patients eligible for colorectal liver metastatectomy as a first proof of concept. Ultimately this will contribute to the development of a diagnostic tool for the comprehensive assessment of CMS4 load in patients with (metastatic) CRC by using [18F]-ALF-FAPI-74 PET/CT molecular imaging, to guide CMS4 subtype-directed therapy decisions.
This Phase Ib trial studies the side effects and best dose of LB-100 and azenosertib for the treatment of patients with metastatic colorectal cancer. Azenosertib blocks a protein that is involved in the repair of damaged DNA, this protein is called WEE1. Inhibiting WEE1 drives cancer cells into a state of cell division without repair of the damaged DNA, resulting in cell death. LB-100 has been shown to make anticancer drugs work better at killing cancer. LB-100 blocks a protein called PP2A. Blocking this protein increases the stress signals for the tumor cells that express PP2A. Research has shown that azenosertib and LB-100 may enhance each others effect when treating metastatic colorectal cancer.
HS-CA102N-103 is a Phase 2, randomized, open label study to evaluate efficacy, safety, and tolerability of CA102N combined with trifluridine/tipiracil (TAS-102) compared to bevacizumab combined with TAS-102 in subjects with metastatic colorectal cancer (mCRC) who failed the standard treatment (for eg, cancer that has relapsed after or is refractory to fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy).
This is an open-label, non-randomized trial with OB-002 monotherapy dose escalation followed by a dose expansion in patients with metastatic colorectal, pancreatic, gastric, breast, or urothelial cancer who have progressed on two or more treatment regimens.
The study is a phase II clinical study. The purpose of the study is to evaluate the efficacy and safety of SBRT combined with Fruquintinib Plus PD-1/CTLA-4 Antibody for Third-line Treatment in mCRC.
This is an open-label phase II study, with the aim of investigating the efficacy and safety of Tislelizumab + Fruquintinib combination therapy in ARID1A-mutated pMMR/MSS metastatic colorectal cancer who have been treated with standard chemotherapy that includes fluoropyrimidine, oxaliplatin, and irinotecan. Patients with hypermutated CRC that carries POLE/POLD1 mutations cannot be included.
The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS), achieved by HX008 or Investigator's Choice Chemotherapy in participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer (mCRC).
RAS mutations are found in nearly half of colorectal cancer patients. However, there is no targeted driver gene drugs have been approved for RAS-mutated patients. For RAS mutant metastatic colorectal cancer, the commonly used treatment regimen is bevacizumab combined with chemotherapy.
The metastatic colo-rectal cancer (especially with hepatic metastatic lesions, but also peritoneal or pulmonary lesions) is a major public health issue, because of its frequency, the heavy treatments and the cost of new therapeutic molecules involved, in particular targeted therapies that can result in specific adverse events. The first-line treatment often consists of a polychemotherapy, which can be associated to a targeted therapy. According to the therapeutic response, patient condition and disease extent, some patients may benefit from prognosis-changing treatments such as surgery of metastases. However, the best morphological response is most of time evidenced after only 6 or 8 cycles of treatment, corresponding to 3 to 4 months. Therapeutic evaluation with FDG PET/CT is validated in several neoplasia (lymphoma, breast cancer). Data on FDG PET evaluation of colic cancer chemotherapy are currently insufficient to propose its use in the usual clinical setting. We thus are going to study the performance of early FDG PET therapeutic evaluation to predict response to first-line chemotherapy in patients with potentially resectable metastases. If early PET diagnostic performances prove satisfying, this approach could become of paramount importance to tailor therapeutic strategy for these patients, with the possibility of early modification of chemotherapy protocol, which is now possible thanks to the existence of therapeutic alternatives (chemotherapy intensification, replacement of oxaliptaine by irinotecan or conversely, replacement of an anti-EGFR by an anti-angiogenic or conversely).
This is a prospective, open, multicenter, randomized controlled phase II study designed to observe the difference of efficacy, adverse events and quality of life between second-line and third-line application of Fruquintinib in patients with metastatic colorectal cancer. The study will evaluate PFS, ORR, OS and safety.