LASP-06: Drug Efficacy in a Three-Arm Survival Study in Kras/p53 Pancreatic Ductal Adenocarcinoma (PDAC) Mice

The Laboratory Animal Sciences Program will 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.

Four treatments will be compared (vehicle and compound of interest at two different concentrations). Mice will be allowed to progress to study end-points, defined as either 20% weight loss or displaying recognizable signs of morbidity, general lack of reflexes, abnormal posture, or visible respiratory distress. Once started on treatments, mice will be frequently monitored by the following:

  • 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

Animals reaching study endpoints (or if found deceased) will be processed 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. The Laboratory Animal Sciences Program will provide collected cryopreserved tissues and blood plasma, as well as a full study evaluation report. Sufficient basic consultation with a subject matter expert is included with the service.

Group

Treatment

Dose/Schedule

Collection at

1

Vehicle

TBD* IP, q4d x 8

Endpoint, X* hrs post-treatment

10 

2

AS1

TBD* IP, q4d x 8

Endpoint, X* hrs post-treatment

15 

3

AS2

TBD* IP, q4d x 8

Endpoint, X* hrs post-treatment

15 

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