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Study of Andrographolides With or Without Capecitabine to Treat Colorectal Cancer

ABSTRACT: The purpose of this study is to determine the efficacy and safety of Andrographolides combined with Capecitabine in treatment of elderly patients with locally advanced or recurrent or metastasis inoperable colorectal cancer

DISEASE(S): Colorectal Neoplasms

PROVIDER: 2155506 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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RNA data of MKN45 tumours treated with ERY974 and/or capecitabine in huNOG mice

Project description:We found that ERY974 shows only moderate antitumor efficacy in MKN45 non-inflamed tumor in huNOG mice. We also observed that ERY974 + capecitabine increases antitumour efficacy in non-inflamed MKN45 tumours. To identify a mechanism of combination effect, we compared RNA expression of MKN45 tumors treated with ERY974, capecitabine, or combination.

2022-08-21 | GSE211373 | GEO

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomized, phase 3 trial.

Project description:The TeloVac study indicated that GV1001 did not to improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC) patients. However, the cytokine examinations of the study suggested that high serum eotaxin levels may predict responses to GV1001. This phase III trial aimed to assess the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated locally advanced and metastatic PDAC. In addition, we proposed potential blood markers to predict response to GV1001 treatment based on correlative studies.

2022-09-03 | GSE212575 | GEO

Pure Estrogen Receptor Antagonists Potentiate Capecitabine Activity in ESR1-mutant Breast Cancer

Project description:The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.

2024-06-01 | GSE266932 | GEO

A phase Ib trial evaluating the safety, efficacy, and immunologic effects of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer

Project description:Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200mg IV every 3 weeks) with either weekly paclitaxel (80mg/m2 weekly) or flat-dose capecitabine (2000mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n=4/13, 95% CI: 10-61%) and 43% for pembrolizumab/capecitabine (n=6/14, 95% CI: 18-71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted.

2023-02-17 | GSE225078 | GEO

Barcode Sequencing Data of Capecitabine Resistant Caco-2 and Irinotecan Resistant HT-29 Cell Lines

Project description:Caco-2 and HT-29 cells were barcoded using the CloneTracker lentiviral barcode library and then irinotecan and capecitabine resistant derivatives of these cell lines were established. Four million barcoded Caco-2 and HT-29 cell were seeded into 15 cm cell culture dishes. When the cells reached confluency, two million cells per dish were seeded into four different 15 cm dishes with 25 mL medium (DMSO Control, Replica A, B, C) and two million cell pellets were stocked as initial cell population.For Caco-2 cell line, mediums in the dishes were changed twice a week with fresh mediums containing IC50 dose (4 months) and subsequently 2x IC50 dose (2 months) of capecitabine, for HT-29 cell line IC50 dose (6 months) of irinotecan. Caco-2 and HT-29 cell lines treated with DMSO were given the same amount of DMSO used in dissolving compounds as fresh medium. Following the end points of six months for each cell line, DNA isolation from harvested cell lines and collected medium of resistant B cell lines were carried out and barcodes were sequenced.

2023-07-11 | E-MTAB-12818 | biostudies-arrayexpress

Correlative studies in Protocol BACCI, which studied Capecitabine, B

Project description:Correlative studies in Protocol BACCI, which studied Capecitabine, B

| PRJNA1066028 | ENA

Correlative studies in Protocol BACCI, which studied Capecitabine, B

Project description:Correlative studies in Protocol BACCI, which studied Capecitabine, B

| PRJNA1066027 | ENA

Radiotherapy Combined With Tislelizumab and Irinotecan in MSS/pMMR Recurrence and Metastatic Colorectal Cancer

Project description:Explore the efficacy of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer patients; To evaluate the safety and tolerability of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer; To evaluate the radiosensitization effects of Tslelizumab and irinotecan;

| 2398597 | ecrin-mdr-crc

Recurrent breakpoint genes in colorectal cancer

Project description:In this study our aim was to document recurrent DNA copy number aberration associated breakpoints in primary tumors of colorectal cancer patients that ultimately received systemic treatment in the context of metastatic disease. Such data can be used to catalogue copy number aberration associated breakpoints and thereby affected genes. To this end, high quality arrayCGH data set of clinically well annotated colorectal cancer specimens was generated using FFPE tumor samples from patients from two phase III clinical trials, namely CAIRO and CAIRO2. arrayCGH data of colorectal cancers of patients from 2 clinical trials. 108 patients were treated with capecitabine first line, 110 patients were treated with capecitabine and irinotecan first line and 134 patients were treated with capecitabine, oxaliplatin and bevacizumab.

2014-11-14 | E-GEOD-63216 | biostudies-arrayexpress

Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

Project description:PURPOSE: Phase II trial to study the effectiveness of combining capecitabine and irinotecan in treating patients who have locally advanced, recurrent, or metastatic colorectal cancer.

| 2006602 | ecrin-mdr-crc

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