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Capecitabine and 131I-huA33 in Patients With Metastatic Colorectal Cancer

ABSTRACT: The purpose of this clinical trial is to determine whether it is safe to treat patients with advanced colorectal cancer, with humanised A33 antibody tagged with radioactive iodine (131I-huA33) in combination with chemotherapy (capecitabine).

DISEASE(S): Colorectal Neoplasms

PROVIDER: 2026348 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Single-cell sequencing of tumor ecosystems in papillary thyroid carcinoma

Project description:The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profiled transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC.Our study illuminates a comprehensive landscape of PTC ecosystem that suggests potential prognostic and therapeutic implications. Our work not only adds dimensions to the biological underpinnings of PTC heterogeneity, but also provides a benchmark dataset for this malignancy.

2021-09-19 | GSE184362 | GEO

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 trametinib and dabrafenib associated with radioactive iodine for the treatment of refractory metastatic differentiated thyroid cancer

Project description:Efficacy of a selective MEK (trametinib) and BRAFV600E (dabrafenib) inhibitors associated with radioactive iodine (RAI) for the treatment of refractory metastatic differentiated thyroid cancer with RAS or BRAFV600E mutation. To evaluate the objective response rate according to RECIST criteria in thyroid cancer patients with metastatic radioactive iodine (RAI) refractory disease, 6 months after a treatment combining in each arm of the phase II trial (patients with RAS mutation or patients with BRAFV600E mutation): - Arm A: 6 weeks of trametinib followed by RAI treatment (5.5 GBq following rhTSH) in patients with RAS mutation - Arm B: 6 weeks of trametinib plus dabrafenib followed by RAI treatment (5.5 GBq following rhTSH) in patients with BRAFV600E mutation

2023-09-01 | E-MTAB-12837 | biostudies-arrayexpress

Efficacy of trametinib and dabrafenib associated with radioactive iodine for the treatment of refractory metastatic differentiated thyroid cancer (KRAS cohort)

Project description:Efficacy of a selective MEK (trametinib) and BRAFV600E (dabrafenib) inhibitors associated with radioactive iodine (RAI) for the treatment of refractory metastatic differentiated thyroid cancer with RAS (current cohort) or BRAFV600E mutation. To evaluate the objective response rate according to RECIST criteria in thyroid cancer patients with metastatic radioactive iodine (RAI) refractory disease, 6 months after a treatment combining in each arm of the phase II trial (patients with RAS mutation or patients with BRAFV600E mutation): - Arm A: 6 weeks of trametinib followed by RAI treatment (5.5 GBq following rhTSH) in patients with RAS mutation - Arm B: 6 weeks of trametinib plus dabrafenib followed by RAI treatment (5.5 GBq following rhTSH) in patients with BRAFV600E mutation

2023-09-01 | E-MTAB-12900 | biostudies-arrayexpress

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.

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Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Colorectal Cancer

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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

Project description:Gut microbiota for radioactive iodine therapy

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Integrating transcriptomics and proteomics to reveal the role of 125I in hepatocellular carcinoma

Project description:Our main research focuses on the intervention of iodine-125 radioactive particles on liver cancer cells, inducing changes in gene expression, which may affect changes in biological characteristics. This provides clues for the potential mechanisms of iodine-125 radioactive particle therapy in liver cancer and offers new targets for disease treatment.

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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

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