Ethics of Mandatory Research Biopsy for Correlative End Points Within Clinical Trials in Oncology

Peppercorn, Jeffrey; Shapira, Iuliana; Collyar, Deborah; Deshields, Teresa L.; Lin, Nancy U.; Krop, Ian E.; Grünwald, Hans; Friedman, Paula N.; Partridge, Ann H.; Schilsky, Richard L.; Bertagnolli, Monica M.

doi:10.1200/jco.2009.27.2443

Cited by 75 publications

(70 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Safety concerns and ethical controversies surrounding research biopsies have been voiced [4]. In particular, there may be concerns regarding the risk of harm without a clearly defined prospect of benefit.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of Research Biopsies in Phase I Clinical Trials: The MD Anderson Cancer Center Experience

et al. 2011

View full text Add to dashboard Cite

Background. Research biopsies are crucial for exploring the impact of novel agents on putative targets. The current study assesses the safety and success rate associated with performing such biopsies.Methods. We reviewed the medical records of 155 consecutive patients who had one or more research biopsies as part of a phase I trial from September 2004 to October 2009.Results. Of 281 research biopsies performed, 118 were paired before and after treatment biopsies (total ‫؍‬ 236 biopsies). The most common sites of biopsy were superficial lymph node (19.9%), followed by liver (16.4%), and then soft tissue (15.7%). Ultrasound-guided biopsies were the most frequent type (53.7%). Among 142 patients who consented for mandatory biopsy, 86.6% had the biopsy performed, compared with 4.4% of 911 patients offered a

show abstract

Section: Introductionmentioning

confidence: 99%

Outcomes of Research Biopsies in Phase I Clinical Trials: The MD Anderson Cancer Center Experience

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Correlative biopsy data has the potential to ascertain target-specific, mechanistic activity of study interventions (2,27). This can provide clues as to how to troubleshoot agents that fail to recapitulate disease activities shown in animals (28) it can inform dosing decisions for phase II studies, eligibility criteria for trials using enrichment designs, or it can provide corroborating evidence that an agent should be advanced into later stages of development.…”

Section: Discussionmentioning

confidence: 99%

Publication and Reporting Conduct for Pharmacodynamic Analyses of Tumor Tissue in Early-Phase Oncology Trials

Freeman

Kimmelman

2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: In principle, nondiagnostic biopsies for pharmacodynamic (PD) studies are carried out to inform decision-making in drug development. Because such procedures have no therapeutic value, their ethical justification requires that results be published. We aimed to assess the frequency of nonpublication of PD data in early phase cancer trials and to identify factors that prevent full publication of data.Methods: We identified a sample of early-phase cancer trials containing invasive nondiagnostic tissue procurement for PD analysis from American Society of Clinical Oncologyand American Association for Cancer Research meeting abstracts published between 1995 and 2005. These trials were followed to publication to determine frequency of nonpublication of PD data. Corresponding authors on early-phase cancer trials using invasive nondiagnostic research procedures were also surveyed to identify factors preventing full publication of PD data.Results: In a sample of 90 trials, 22.2% (20 trials) resulted in no trial publication. Of published trials expected to contain PD reports, 16 (17.8%) did not include any PD data, and 21 (23.3%) reported incomplete PD data. We surveyed 92 authors; nonpublication was regarded as a frequent occurrence, and the most commonly cited barrier to full publication of PD data was strategic considerations in publication (58.8% of responding authors).Conclusions: Our results suggest ways that investigators, study planners, and reviewers can improve the burden/knowledge value balance in PD studies. Clin Cancer Res; 18(23); 6478-84. Ó2012 AACR.

show abstract

“…Taking into account some basic ethics principles, it is higly recomended to include such patients in prospective clinical trials and to perform consecutive molecular analyses of cancer tissue, at different time points, in our dramatic search to understand the biologic bases of response or resistance to novel interventions. The main goal is to develop prognostic and predictive biomarkers that will help clinical decision making process [25].…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of Molecular Markers during Natural History in Metastatic Melanoma: Ethical Issues and Lessons to Learn

Eugeniu¹,

Zaharie²,

Serban³

et al. 2016

J Integr Oncol

View full text Add to dashboard Cite

Objective: Malignant melanoma with brain metastases is associated with a higher risk of death. No specific treatments were demonstrated to be useful in a such situation. Drugs as temozolomide orally or new targeted treatments showed significant objective response rates, even complete regression. Such responses could be obtained using new strategies based on dynamic changes over time of some molecular markers. Elements of ethics should be taken into account in order to adapt treatment and avoid resistance. Methods:The case of a 59-year old male with a primary cutaneous melanoma of the trunk, treated at Cancer Institute "Ion Chiricuta" from August 2001 is presented. After multiple loco-regional relapses, the patient developed brain metastases and started temozolomide 150 mg once daily, five days, every 4 weeks, 6 cycles with concurrent whole brain external radiotherapy. Comparative immunostaining including proliferation and pro-apoptotic molecular markers between the initial diagnosis (2001), before (2005) and after (2008) temozolomide treatment was performed.Result: Nine months after the start of temozolomide treatment, complete response was confirmed by magnetic resonance imaging. Overall cancer specific survival was 41 months. Ki-67, cyclin E, HMB-45 expression and Bax/ Bcl-2 ratio increased during almost 10 years of treatment and follow-up. Bcl-2 staining was absent at the last analysis. Only p53 and Bax expression doesn't changed during treatment. Conclusion:It seems that metastatic melanoma cells lost some of pro-apoptotic markers and overexpressed markers of proliferation. Predictive markers of response and resistance were actively identified; their combination and dynamic over time could help the oncologist to select those metastatic patients with highest chances of response. Dynamic changes of these molecular markers would guide treatment and the overall core strategy. Serial biopsies and tissue analyses become a challenging ethical issue. Empiric treatments based on a unique tumor signature should be modified using an adaptive approach.

show abstract

Ethics of Mandatory Research Biopsy for Correlative End Points Within Clinical Trials in Oncology

Cited by 75 publications

References 43 publications

Outcomes of Research Biopsies in Phase I Clinical Trials: The MD Anderson Cancer Center Experience

Outcomes of Research Biopsies in Phase I Clinical Trials: The MD Anderson Cancer Center Experience

Publication and Reporting Conduct for Pharmacodynamic Analyses of Tumor Tissue in Early-Phase Oncology Trials

Dynamic Changes of Molecular Markers during Natural History in Metastatic Melanoma: Ethical Issues and Lessons to Learn

Contact Info

Product

Resources

About