Dataset Information

Study to investigate cetuximab plus irinotecan as rechallenge 3rd-line treatment of kras, nras and braf wild-type irinotecan-pretreated metastatic colorectal cancer patients progressing after an initial response to a 1st-line cetuximab-containing therapy and a standard 2nd-line.

ABSTRACT: Primary objectives: to evaluate, in terms of Overall Response Rate (ORR), the activity of cetuximab plus irinotecan as rechallenge third line treatment of RAS (K- and N-RAS, codons 12, 13, 59, 61, 117, 146) and BRAF (V600E) wild-type, irinotecan-resistant, mCRC patients progressing after an initial response to a first-line irinotecan- and cetuximab-containing therapy and a second-line with FOLFOXIRI/FOLFOX/XELOX plus bevacizumab. Primary endpoints: The primary endpoint of this study is overall response rate (ORR) ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria. The determination of clinical response will be based on investigator-reported measurements. Responses will be evaluated with a chest and abdominal computed tomography (CT) scan every 8 weeks. Patients who do not have an on-study assessment will be included in the analysis as non-responders.

DISEASE(S): Metastatic Colorectal Cancer,Carcinoma Colon Retto Metastatico Nras,kras E Braf Non Mutato.,Metastatic Colonrectal Cancer Kras, Nras And Braf Wild Type.

PROVIDER: 2533105 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies about complex mixtures effects. PHY906 is a long used four herb TCM formula employed as adjuvant to relieve side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when PHY906 was combined. Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of Irinotecan by PHY-906 in a well-characterized pre-clinical model; PHY-906 and Irinotecan were administered orally to female BDF-1 mice bearing subcutaneous Colon 38 tumors. We observed that 1) individually PHY-906 and Irinotecan induce distinct alterations in tumor, liver and spleen; 2) PHY-906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of Irinotecan, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection. Most importantly, PHY-906 together with Irinotecan triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response. Four groups of BDF-1 mice bearing colon 38 tumors were treated with Phosphate Buffered Saline (PBS) (n=10), PHY-906 (n=10), Irinotecan (CPT-11, Camptosar(TM)) (n=10) or the combination PHY-906 and Irinotecan (n=10). Tumor (38 samples), spleen (38 samples), and liver (35 samples) tissues were removed and frozen for total RNA isolation and subsequent microarray hybridization. There were a total of 111 samples representing 12 treated tissue groups with 8 to 10 biological replicates each. A reference sample was generated from a pool of mixed normal mouse tissue.

Dataset Information

Study to investigate cetuximab plus irinotecan as rechallenge 3rd-line treatment of kras, nras and braf wild-type irinotecan-pretreated metastatic colorectal cancer patients progressing after an initial response to a 1st-line cetuximab-containing therapy and a standard 2nd-line.

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