Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer

Abstract

BackgroundThe time between the diagnosis of cancer and a planned definitive surgical procedure offers a strong and direct approach for assessing the impact of interventions (including lifestyle interventions) on the biology of the target tissue and the tumor. Despite the many strengths of presurgical models, there are practical issues and challenges that arise when using this approach.Purpose/MethodsWe recently completed an NIH-funded phase II trial that utilized a presurgical model in testing the comparative effects of flaxseed supplementation and/or dietary fat restriction on the biology and biomarkers associated with prostatic carcinoma. Herein, we report the rationale for our original design, discuss modifications in strategy, and relay experiences in implementing this trial related to the following topics: (1) subject accrual; (2) subject retention; (3) intervention delivery; and (4) retrieval and completion rates regarding the collection of paraffin-embedded and fresh frozen prostate tissue, blood, urine, ejaculate, anthropometric measures and survey data.ResultsThis trial achieved its accrual target, i.e., a racially-representative (70% white, 30% minority) sample of 161 participants, low rates of attrition (7%); and collection rates that exceeded 90% for almost all biospecimens and survey data. While the experience gained from pilot studies was invaluable in designing this trial, the complexity introduced by the collection of several biospecimens, inclusion of a team of pathologists (to provide validated readings), and shifts in practice patterns related to prostatectomy, made it necessary to revise our protocol; lessons from our experiences are offered within this article.ConclusionsWhile our experience specifically relates to the implementation of a presurgical model-based trial in prostate cancer aimed at testing flaxseed-supplemented and fat-restricted diets, many of the lessons learned have broad application to trials that utilize a presurgical model or dietary modification within various cancer populations.

A Pilot Study Comparing the Effect of Flaxseed, Aromatase Inhibitor, and the Combination on Breast Tumor Biomarkers

“…Although the “Window of Opportunity” setting provides the chance to assess differences in tumor biology from biopsy to surgery, the narrow time window for recruitment is a concern. Our recruitment success was comparable to a similar study of flaxseed in prostate cancer patients between biopsy and surgery (46, 47). Future studies would require a multi-center approach, or alternatively, the development of intermediate biomarkers of prognosis.…”

Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery

“…A detailed description of the methods used in this trial are reported elsewhere (26). In brief, the trial employed a 2×2 factorial design, with the presence or absence of the two factors, flaxseed supplementation and dietary fat restriction, defining the following four treatment arms: 1) control (usual diet); 2) flaxseed-supplemented diet; 3) low-fat diet; and 4) flaxseed-supplemented, low-fat diet.…”

Predictors of Willingness to Participate in Window-of-Opportunity Breast Trials

“…However, our estimates are lower than the other measures presented in earlier research papers for accrual once eligibility was documented. 5,8,19,21 Our survey investigated numerous factors that may impact a woman's decision to participate in preoperative chemoprevention trials. Our aim was to identify variables that may limit recruitment to these preoperative breast cancer chemoprevention studies.…”