Assessment of Drug Efficacy in a Survival Study

• Evaluates drug efficacy in a three, four, or five arm study format. 
• Includes cryopreserved tissues and blood plasma. 
• Includes quantitative assessment of up to five informative biomarkers by immunohistochemistry. 
• Available in Kras/p53 pancreatic ductal adenocarcinoma or Kras/p53 non-small cell lung cancer mice.
• Includes sufficient basic consultation with a subject matter expert.

Process

• Induce breed 50 KPC animals with the intent of generating a cohort of 40 animals with confirmed tumor-load matching the following enrollment criteria: 
  • Female mice are considered eligible for enrollment when ultrasound examination within 24 hours reveals 1 or 2 tumors, with the largest size being 6–11 mm and a combined tumor volume of 100–350 mm3.
  • Animals with three or more tumors per organ; cystic tumors; signs of intestinal, pancreatic, or gall bladder duct occlusions; or otherwise moribund/showing signs of dilapidation will not be included in the study.
• Compare four treatments (vehicle and compound of interest at two different concentrations).
• Allow mice to progress to study end-points, defined as either 20 percent weight loss or displaying recognizable signs of morbidity, general lack of reflexes, abnormal posture, or visible respiratory distress.
• Monitor mice frequently once started on treatments, including:
  • Daily observations by trained personnel
  • Recording of daily weights for all mice enrolled in the study
  • Monitoring for signs of abdominal/ascitic fluid accumulation
  • Observations of tumor progression by size/volume measurement using ultrasound imaging (two weekly sessions or less frequently as directed by study design and/or drug administration regimen)
  • Weekly mandibular blood collection (up to 100µl of whole blood) and storage for subsequent biomarker assessment
• Process animals reaching study endpoints (or if found deceased) for necropsy and blood collection (if “warm” necropsy) to prepare multi-organ blocks/tissue slides for pathology evaluation and biomarker assessment. 
•  If requested, the Laboratory Animal Sciences Program will prepare flash-frozen samples of pancreatic tumor, adjacent non-pathologic pancreas, and other organs.
• The estimated completion time for this service is 10 months.

TBD* - Dosing concentrations will be provided prior to initiation of study by the requestor.