Zlecenie 8917326 - Rozwój kliniczny innowacyjnego kandydata na lek w terapii...

in tumor-bearing mice 1.1 Animals Female mice of preferably NSG immune-compromised strain, age-matched, provided by the Contractor. N=4 mice per group. 1.2 Cell line Animals will be inoculated either subcutaneously or orthotopically with HCC38 human cancer cells (cells will be provided by the Contractor). Contractor should provide information on the tumor growth kinetics. 1.3 Compound administration After the tumors reach the volume of around 200-250 mm3, mice will be administered with the compound or the vehicle. The compound will be provided by the Sponsor together with formulation instructions. Compound will be prepared freshly before dosing. Contractor must specify additional costs (if any) for dosing on Saturday and/or Sunday. 1.4 Evaluated parameters Individual body weights (BW) will be monitored daily. Tumor volume (TV) will be measured at randomization and at termination. Contractor should inform about the raw data availability during the study course and updates frequency. 1.5 Sample collection and shipment All groups will have blood collected for plasma, 4h after the last administration: survival sampling in groups 1-4, terminal sampling in group 5. Additionally, blood for plasma will be also terminally collected 24h after the last dose from groups 1-4. All groups will have terminal collection of the tumors: 1-4: 24h after the last dose, 5: 4h after the last dose. Tumors will be divided in half, both halves will be snap frozen and moved to -80oC. Samples should be stored at -80oC until shipment on dry ice to Sponsor. Shipment costs to Poland should be included in the quotation. It should be stressed, that the permission from Central Veterinary Inspectorate is obligatory to import biological samples from outside the European Union, which will be the responsibility of the Sponsor. 1.6 Report Non-GLP study and report. 2. Efficacy study in immunodeficient mice 2.1 Animals Female mice of immunodeficient strain, preferably NSG (the strain should be the same as for the PK/PD study), age-matched, provided by the Contractor. N=10 mice per group. 2.2 Cell line Animals will be inoculated either subcutaneously or orthotopically with HCC38 human cancer cells (cells will be provided by the Contractor). Contractor should provide information on the tumor volume kinetics and available reference compounds together with tumor growth inhibition. 2.3 Compound administration The compound will be provided by the Sponsor together with formulation instructions. Compound will be prepared freshly before dosing. Compound or formulation will be administered per os (PO), with once daily (QD) schedule, for about 28 days. Contractor must provide an appropriate reference compound to test alongside our Compound X. Contractor must specify additional costs (if any) for dosing on Saturday and/or Sunday. Each week of the additional dosing, BW and TV measurements should be also quoted. 2.4 Evaluated parameters Clinical signs will be monitored daily throughout the dosing period. Tumor volume (TV) will be measured 2-3 times a week; body weight (BW) will be measured daily. Contractor should inform about the raw data availability during the study course and updates frequency. 2.5 Sample collection Terminal blood and organ sampling: 4h after the last dose mice will have blood (for plasma) and tumors collection. Tumors will be divided in half, both halves will be snap frozen and moved to -80oC. Samples should be stored at -80oC until shipment on dry ice to Sponsor. Shipment costs to Poland should be included in the quotation. It should be stressed, that the permission from Central Veterinary Inspectorate is obligatory to import biological samples from outside the European Union, which will be the responsibility of the Sponsor. 2.6 Report Non-GLP study and report.