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

January 1, 2008 Human Health and Nutrition Data 0 Comments

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

Year: 2008
Authors: Demark-Wahnefried, W. George, S.L. Switzer, B.R. Snyder, D.C. Madden, J.F. Polascik, T.J. Ruffin, M.T. Vollmer, R.T.
Publication Name: Clinical Trials
Publication Details: Vol 5; Pages 262-272.


The 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. We 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. This 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 bio-specimens, 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. While 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. (Author's Abstract)
Lifestyle factors are postulated to play a key role in the development and progression of prostate cancer (PC) as supported by one large-scale randomized controlled trial (RCT), such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT). However, these type of trials are both time- and resource-intensive. The presurgical or preoperative model has been proposed to evaluate a wide spectrum of interventions in various site-specific cancers. In this paper, the authors describe their research with flaxseed and its potential benefits to reduce PC and high grade prostatic intraepithelial neoplasia (HGPIN), in particular three studies: (1) an in vitro experiment that exposed three major PC cell lines (LNCaP, DU-145, and PC-3) to flaxseed-derived mammalian lignans; (2) an animal feeding experiment that tested a 5% flaxseed-supplemented diet against an isocaloric-controlled diet in transgenic mice genetically programmed to develop PC; and (3) a pilot feasibility study of a low-fat, flaxseed-supplemented diet in men found to have HGPIN or atypia. In all of these studies, flaxseed derived lignans, flaxseed itself or the flaxseed diet with concomitant dietary fat restriction were found to significantly hinder prostatic growth (via decreased proliferation and increased apoptosis in both malignant and benign tissue), and/or reduce tumour burden. A pilot study was conducted which supported these results. This evidence led support to undertake a phase II trial to test the comparative effects of flaxseed-supplementation and/or dietary fat restriction on PC. The paper describes strategies and methods used in PC research that may assist others who contemplate chemoprevention studies that utilize presurgical models for cancers of the breast, cervix, head and neck, bladder, and colon. (Editor's comments)

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