scholarly journals Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial

JAMA Oncology ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. e193332 ◽  
Author(s):  
Amylou C. Dueck ◽  
Howard I. Scher ◽  
Antonia V. Bennett ◽  
Gina L. Mazza ◽  
Gita Thanarajasingam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Patient Perspective ◽  
Cancer Clinical Trial ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Castration Resistant

scholarly journals A DREAM Challenge to Build Prediction Models for Short-Term Discontinuation of Docetaxel in Metastatic Castration-Resistant Prostate Cancer

2017 ◽  
pp. 1-15 ◽  
Author(s):  
Fatemeh Seyednasrollah ◽  
Devin C. Koestler ◽  
Tao Wang ◽  
Stephen R. Piccolo ◽  
Roberto Vega ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
High Risk ◽  
Adverse Events ◽  
Clinical Features ◽  
Prediction Models ◽  
Castration Resistant Prostate Cancer ◽  
Early Discontinuation ◽  
Castration Resistant

Purpose Docetaxel has a demonstrated survival benefit for patients with metastatic castration-resistant prostate cancer (mCRPC); however, 10% to 20% of patients discontinue docetaxel prematurely because of toxicity-induced adverse events, and the management of risk factors for toxicity remains a challenge. Patients and Methods The comparator arms of four phase III clinical trials in first-line mCRPC were collected, annotated, and compiled, with a total of 2,070 patients. Early discontinuation was defined as treatment stoppage within 3 months as a result of adverse treatment effects; 10% of patients discontinued treatment. We designed an open-data, crowd-sourced DREAM Challenge for developing models with which to predict early discontinuation of docetaxel treatment. Clinical features for all four trials and outcomes for three of the four trials were made publicly available, with the outcomes of the fourth trial held back for unbiased model evaluation. Challenge participants from around the world trained models and submitted their predictions. Area under the precision-recall curve was the primary metric used for performance assessment. Results In total, 34 separate teams submitted predictions. Seven models with statistically similar area under precision-recall curves (Bayes factor ≤ 3) outperformed all other models. A postchallenge analysis of risk prediction using these seven models revealed three patient subgroups: high risk, low risk, or discordant risk. Early discontinuation events were two times higher in the high-risk subgroup compared with the low-risk subgroup. Simulation studies demonstrated that use of patient discontinuation prediction models could reduce patient enrollment in clinical trials without the loss of statistical power. Conclusion This work represents a successful collaboration between 34 international teams that leveraged open clinical trial data. Our results demonstrate that routinely collected clinical features can be used to identify patients with mCRPC who are likely to discontinue treatment because of adverse events and establishes a robust benchmark with implications for clinical trial design.

scholarly journals Comparison of weekly and daily recall of pain as an endpoint in a randomized phase 3 trial of cabozantinib for metastatic castration-resistant prostate cancer

2021 ◽  
pp. 174077452110095
Author(s):  
Elisabeth M Schaffer ◽  
Ethan M Basch ◽  
Gisela M Schwab ◽  
Antonia V Bennett
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Treatment Response ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Drug Trial ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Castration Resistant ◽  
The Mean

Introduction Scant evidence reveals whether the use of weekly versus daily pain ratings leads to meaningful differences when measuring pain as a clinical trial outcome. We compared the ability of weekly ratings and descriptors of daily ratings to evaluate pain as an endpoint in a randomized phase 3 drug trial. Methods Participants ( n = 119) with metastatic castration-resistant prostate cancer were randomized to treatment arms and rated their pain on the average and at its worst during a baseline week and at weeks 3, 6, and 12 of study treatment. For each reporting period, participants rated their pain daily for 7 days. On day 7, participants rated their pain over the prior 7 days. We estimated mean differences and intraclass correlation coefficients of the weekly ratings and the mean and the maximum daily ratings. We compared the ability of the weekly ratings and the daily rating descriptors to detect change in pain and evaluated the agreement of the weekly rating and the mean daily rating of pain at its worst to detect treatment response. Results For both pain constructs, the weekly rating was consistently higher than the mean daily rating and lower than the maximum daily rating yet was moderately to highly correlated with both daily rating descriptors (intraclass correlation coefficient range = 0.55–0.94). The weekly rating and the daily rating descriptors consistently detected change in pain for the study sample and participant subgroups. Substantial agreement existed between the weekly rating and the mean daily rating of pain at its worst when used with trial protocol opioid criteria to detect treatment response (Cohen’s κ = 0.71). Conclusion Use of daily over weekly ratings delivered no added benefit in evaluating pain in this clinical trial. This study is the first to compare weekly and daily recall to measure pain as an endpoint in a randomized phase 3 drug trial, and the pattern of differences in ratings that we observed is consistent with other recent evaluations of weekly and daily symptom reporting.

scholarly journals Enzalutamide Versus Abiraterone as a First-Line Endocrine Therapy for Castration-Resistant Prostate Cancer: Protocol for a Multicenter Randomized Phase 3 Trial (Preprint)

2018 ◽  
Author(s):  
Isao Hara ◽  
Shimpei Yamashita ◽  
Satoshi Nishizawa ◽  
Kazuro Kikkawa ◽  
Toshio Shimokawa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Cancer Patients ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Antitumor Effects ◽  
Castration Resistant ◽  
To Receive

BACKGROUND Recent large-scale randomized studies have demonstrated that 2 new hormone preparations (abiraterone and enzalutamide) prolong survival in docetaxel-treated or -naïve castration-resistant prostate cancer patients. However, no studies have directly compared antitumor effects between these 2 agents, and no clear guidelines are available for choosing between them. OBJECTIVE The objective of this clinical study is to compare antitumor effects and adverse events between abiraterone and enzalutamide by allocating castration-resistant prostate cancer patients deemed not indicated for docetaxel treatment to receive either of the 2 agents. METHODS This study is an open-label, comparative study allocating castration-resistant prostate cancer patients to abiraterone or enzalutamide treatment arms (allocation factors: age <70 vs ≥70 years, and presence vs absence of metastases) and assessing the treatment results. Each arm will contain 25 patients. On confirmation of prostate-specific antigen failure or progression on imaging, patients undergo crossover to receive the alternative study drug. The primary end point is prostate-specific antigen response rate (percentage of patients with a decrease in prostate-specific antigen level by ≥50%) in the abiraterone and enzalutamide treatment arms. RESULTS Recruitment started in May 2016, and 13 patients have been recruited so far. We expect to complete enrollment by December 2020. CONCLUSIONS Recently, cross-resistance between abiraterone and enzalutamide has been an issue of focus. Urologists thus tend to prefer docetaxel rather than sequential therapies using 2 hormonal preparations after the progression of a first hormonal preparation. From that perspective, our clinical trial is rather out of fashion. Nevertheless, we assume that many patients receive hormonal sequential therapy in the actual clinical setting, since most such patients cannot receive chemotherapeutic agents due to old age or poor performance status. This is why we are attempting this randomized clinical trial comparing abiraterone versus enzalutamide. We will try to identify which drug is suitable for initial hormonal therapy among castration-resistant prostate cancer patients who do not meet the indications for docetaxel therapy in terms of not only antitumor effect, but also adverse events and quality of life. CLINICALTRIAL University Hospital Medical Information Network UMIN000022102; https://upload.umin.ac.jp /cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025463 (Archived by WebCite at http://www.webcitation.org/70xaQfGlJ)

The effect of low-dose GTx-758 on free testerone levels in men with metastatic castration resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 60-60 ◽  
Author(s):  
Evan Y. Yu ◽  
Robert H. Getzenberg ◽  
Jordan Smith ◽  
Michael L. Hancock ◽  
Ronald Tutrone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Side Effects ◽  
Adverse Events ◽  
Bone Turnover ◽  
Phase Ii ◽  
Low Dose ◽  
Hot Flashes ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

60 Background: Luteinizing hormone-releasing hormone (LHRH) agents used for androgen deprivation therapy (ADT) were designed to lower total testosterone (T) levels to those achieved by orchiectomy for palliative care of advanced prostate cancer. This castration equivalent level was based upon the lower limits of quantitation (50ng/dL) of outdated assays. Contemporary assays reveal that actual total T levels in men after orchiectomy are significantly lower (<20ng/dL), with 30 to 40% of men on LHRH agonists not achieving that level. There is growing literature showing that lower T levels correlate with improved outcomes. Additionally, the biologically active form of T is unbound, free T. GTx-758 (Capesaris) is an oral estrogen receptor α agonist that increases sex hormone binding globulin (SHBG), lowers free T levels, and ameliorates estrogen deficiency side effects associated with ADT. Methods: In a phase II open label study (G200712), 38 men with metastatic castration resistant prostate cancer (mCRPC) were continued on their current form of ADT along with a low dose of GTx-758, 125 mg, for at least 90 days. Exclusion criteria included men at increased risk for venous thrombolic events (VTE). Results: The initial 14 patients in this trial completed 90 days on study and are evaluable for select trial endpoints. All treated men had a greater than or equal to a 150% increase in SHBG levels. Eleven of the 14 men began the study with suboptimal castration (free T >0.7 pg/ml) and 91% (10 out of 11) of these men became optimally castrated by day 90. Four out of 14 patients had a more than 45% decrease in prostate-specific antigen. Stable or improved hot flashes and bone turnover markers were observed in 71% and 73% of treated men, respectively. While some patients experienced adverse events, none were vascular related and there were no serious adverse events or VTEs. Conclusions: The majority of patients on an LHRH agonist enrolled in this phase II study had suboptimal levels of free T that were further lowered by GTx-758 administration. GTx-758 treatment resulted in stabilization and/or improvement in reported hot flashes and bone turnover, two major side effects of ADT. While the phase II clinical trial is ongoing, and full results are forthcoming, these preliminary findings show that 125 mg of GTx-758 has clinical effectiveness and is well tolerated. Exploration of 250 mg a day is planned. Clinical trial information: NCT01615120.

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