abstract: Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery - Variability of Poly (ADP-Ribose) Polymerase Activity.

Wiki:  Poly ADP ribose polymerase: Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death.

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 Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery - Variability of Poly (ADP-Ribose) Polymerase Activity.

Abstract

Purpose: 

The aim of this study was to evaluate the feasibility of phase 0 trials in the setting of a routine surgical procedure. Logistic considerations, tissue sampling and handling, and variability of a biomarker during surgery, in here activity of poly(ADP-ribose) polymerase, were evaluated. 

Experimental design: 

Patients with highly suspicious or proven diagnosis of advanced ovarian cancer, planned for debulking surgery were asked to allow sequential tumor biopsies during surgery. Biopsies were frozen immediately and poly (ADP-ribose) polymerase activity was measured subsequently. 

Results: 

Baseline biopsies were obtained from eight patients after a median time of 88 minutes (minimum of 50 to maximum of 123 minutes). Second and third biopsies were obtained after a median of 60 (32-96) and 101 (79-130) minutes, respectively. Mean tumor load was 44% (5%-100%), with a cellular viability of 98% (85%-100%). Median baseline PARP activity was 1035 pg/ml (range: 429-2663 pg/ml). The observed inter-patient variability at baseline was large: standard deviation was 769 before and 0.59 after natural log transformation. 

Conclusions: 

Conducting phase 0 trials during surgery seems to be feasible in terms of logistic considerations. In preparation of a phase 0 trial during surgery, a feasibility study like this should be conducted to rule out major interactions of the surgical intervention with respect to the targeted biomarker.