Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group Journal Article
| Authors: | Scher, H. I.; Halabi, S.; Tannock, I.; Morris, M.; Sternberg, C. N.; Carducci, M. A.; Eisenberger, M. A.; Higano, C.; Bubley, G. J.; Dreicer, R.; Petrylak, D.; Kantoff, P.; Basch, E.; Kelly, W. K.; Figg, W. D.; Small, E. J.; Beer, T. M.; Wilding, G.; Martin, A.; Hussain, M. |
| Article Title: | Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group |
| Abstract: | Purpose: To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods: A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results: The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or "no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion: PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit. © 2008 by American Society of Clinical Oncology. |
| Keywords: | treatment outcome; clinical feature; clinical trial; disease course; review; cancer growth; patient selection; validation process; clinical trials as topic; research design; outcome assessment; methodology; adenocarcinoma; prostate specific antigen; cancer pain; practice guideline; pathology; outcome assessment (health care); prostate cancer; prostate-specific antigen; prostatic neoplasms; imaging system; standard; blood; disease progression; prostate tumor; bioassay; endpoint determination; pain assessment; testosterone; bone scintiscanning; drug exposure; guidelines as topic |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 26 |
| Issue: | 7 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2008-03-01 |
| Start Page: | 1148 |
| End Page: | 1159 |
| Language: | English |
| DOI: | 10.1200/jco.2007.12.4487 |
| PUBMED: | 18309951 |
| PROVIDER: | scopus |
| PMCID: | PMC4010133 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 189" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus" |
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