Ineligibility of prostate cancer patients in the VA Connecticut Healthcare System (VACHS) to participate in clinical trials due to comorbidities

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5169-5169
Author(s):  
T. M. Mayer ◽  
W. K. Kelly ◽  
J. Concato ◽  
H. Chao
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Healthcare System ◽  
Patient Population ◽  
Performance Status ◽  
Phase Iii ◽  
Medical Conditions ◽  
Eligibility Criteria ◽  
Major Phase

5169 Background: A large proportion of prostate cancer patients receive their care within the VA Healthcare System. As this is a population affected by complex comorbidities, they may be underrepresented in oncology clinical trials. Our objective was to quantify the frequency with which castrate resistant prostate cancer (CRPC) patients in VACHS would be excluded from major phase III randomized controlled trials. Methods: We reviewed records of all prostate cancer patients at the VACHS between 2004–2007 and identified patients with CRPC. We reviewed eligibility criteria of 24 major phase III clinical trials, from 2006 onwards, studying investigational drugs for CRPC and created a “master list” (ML) of the most pertinent criteria. We analyzed our patient population according to both the ML criteria and to the TAX327 study criteria. Results: We identified 106 patients with CRPC, excluded 7 patients with insufficient medical records, and analyzed 99 patients. Performance status and life expectancy could not be accurately assessed from most charts and were excluded as specific criteria (though reflected in other serious medical condition). Major reasons for exclusion according to ML/TAX327 criteria include: 10/10 other malignancy within 5 years; 11/14 abnormal laboratory parameters; 27/30 other serious medical conditions; 3/4 abnormal cardiac function. ML list only exclusions: 5 active angina; 1 unstable DM; 1 major GI surgery; 1 contraindication to steroids. Serious medical conditions included: active cardiac disease, dementia, serious neurologic, psychiatric, vascular, pulmonary or hematologic disease, and poor performance status or compliance. Overall, 45% (45/99) of patients were excluded when using both the ML and TAX327 criteria. Conclusions: Approximately half of CRPC patients in the VACHS between 2004–2007 did not meet eligibility criteria for major therapeutic trials for CRPC. This retrospective review demonstrates that VA patients are underrepresented in randomized clinical trials for CRPC and are a special population due to their complex comorbidities. These findings underscore the importance of designing better clinical trials for CRPC with less barriers for this underrepresented but common patient population. No significant financial relationships to disclose.

Clinical fracture associated with androgen deprivation therapy: A retrospective study of early phase clinical trial cohorts.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 234-234
Author(s):  
Zin Myint ◽  
Charles Kunos
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Radiation Therapy ◽  
Adverse Events ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Early Phase ◽  
Performance Status ◽  
Risk Of Fracture ◽  
Common Grade

234 Background: Androgen deprivation therapy (ADT) is the mainstay treatment in both locally advanced and metastatic prostate cancer. Unfortunately, ADT is associated with rapid loss of bone mineral density (a surrogate for fracture risk) within the first 12 months of initial therapy. Methods: A retrospective review of early phase NCI clinical trials from 2006 to 2013 was conducted to assess the risk of fracture for prostate cancer patients treated with ADT. Results: Seven clinical trials of prostate cancer patients who received ADT between 2006 and 2013 were identified. A total of 464 patients were enrolled in the trials. Patient median age was 64 years, the majority were white (90%), and had good performance status. The median baseline prostate specific antigen level was 29.3 ng/ml and the majority of patients had a Gleason score pattern of >7 (71%). Disease was characterized as involving bone only in 43% of patients and multiple sites (bone, node and/or visceral) in 35%. Of 381 patients for which data were available, 36% received prior hormonal therapy, 37% underwent surgical castration, and 16% received radiation therapy. The most common grade 1-2 adverse events reported in the 7 trials were fatigue (36%), followed by hot flashes (27%), anemia (17%) and hyperglycemia (15%). The most common grade >3 adverse events reported were hypertension and hyperglycemia (3% each). Of the total 464 patients, 7 (0.4%) reported having a fracture (5 were baseline and 2 developed while on treatment). Conclusions: Our study reconfirms the association between clinical fracture and ADT exposure; however, the incidence of fracture rate was less than 1%, which was lower than the published population-based cohorts. The difference could be attributed to short-term ADT exposure, and short-duration of follow up. Clinicians should educate patients about risk of fracture with ADT and offer bone health agent earlier in patients at high risk for fracture and also with underlying co-morbidities such as diabetes, poor performance status, chronic steroid use, or undergo radiation therapy.

scholarly journals Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Erlend Skaga ◽  
Marthe Andrea Skretteberg ◽  
Tom Børge Johannesen ◽  
Petter Brandal ◽  
Einar O Vik-Mo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Performance Status ◽  
Geographical Area ◽  
Eastern Cooperative Oncology Group ◽  
University Hospital ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Eligibility Criteria ◽  
Phase Iii Trials

Abstract Background The survival rates in population-based series of glioblastoma (GBM) differ substantially from those reported in clinical trials. This discrepancy may be attributed to that patients recruited to trials tend to be younger with better performance status. However, the proportion and characteristics of the patients in a population considered either eligible or ineligible for trials is unknown. The generalizability of trial results is therefore also uncertain. Methods Using the Cancer Registry of Norway and the Brain Tumor Database at Oslo University Hospital, we tracked all patients within a well-defined geographical area with newly diagnosed GBM during the years 2012–2017. Based on data from these registries and the medical records, the patients were evaluated for trial eligibility according to criteria employed in recent phase III trials for GBM. Results We identified 512 patients. The median survival was 11.7 months. When we selected a potential trial population at the start of concurrent chemoradiotherapy (radiotherapy [RT]/ temozolomide [TMZ]) by the parameters age (18–70 y), passed surgery for a supratentorial GBM, Eastern Cooperative Oncology Group (ECOG) ≤2, normal hematologic, hepatic and renal function, and lack of severe comorbidity, 57% of the patients were excluded. Further filtering the patients who progressed during RT/TMZ and never completed RT/TMZ resulted in exclusion of 59% and 63% of the patients, respectively. The survival of patients potentially eligible for trials was significantly higher than of the patients not fulfilling trial eligibility criteria (P < .0001). Conclusions Patients considered eligible for phase III clinical trials represent a highly selected minority of patients in a real-world GBM population.

scholarly journals Performance Status Restriction in Phase III Cancer Clinical Trials

2020 ◽  
Vol 18 (10) ◽  
pp. 1322-1326 ◽  
Author(s):  
Joseph Abi Jaoude ◽  
Ramez Kouzy ◽  
Walker Mainwaring ◽  
Timothy A. Lin ◽  
Austin B. Miller ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Related Factors ◽  
Factors Associated ◽  
Toxicity Monitoring ◽  
Fda Approval ◽  
Ecog Ps

Background: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS. Methods: Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time. Results: In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS. Conclusions: Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.

Phase II trial of paclitaxel in front-line therapy of hormone refractory metastatic prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15628-15628
Author(s):  
T. Kolevska ◽  
D. Goldstein ◽  
C. Davis ◽  
L. Fehrenbacher
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Metastatic Prostate Cancer ◽  
Performance Status ◽  
Disease Assessment ◽  
Hormone Refractory Prostate Cancer ◽  
Elderly Men ◽  
Eligibility Criteria ◽  
Psa Progression ◽  
Hormone Refractory

15628 Hormone refractory prostate cancer patients have poor prognosis with median survival of only 16 months. They are frequently elderly men with many co-morbid conditions unable to tolerate treatments with substantial toxicity. Docetaxel, the only drug shown to prolong survival causes significant toxicities, requires steroids administration, may cause poorly reversible neuropathy and requires long infusion times, all limiting its use in elderly men that are mostly affected by hormone refractory prostate cancer. Abraxane is a novel agent delivering paclitaxel without steroids, requires only 30 minutes infusion times and low toxicity potential that may be effective and more tolerable in patients with prostate cancer. The goal of our study is to evaluate the effectiveness and toxicity of Abraxane in first line chemotherapy of men with hormone refractory prostate cancer. Considering the favorable toxicity profile of Abraxane and in an effort to make our results applicable to the majority of prostate cancer patients we are including men with performance status of 2. Main eligibility criteria are: hormone refractory metastatic prostate cancer documented by PSA progression, no prior chemotherapy, PSA >5 and performance status 0–2. Primary endpoint is efficacy based on PSA response. Secondary endpoints are time to PSA progression, overall survival, and toxicities. The clinical trial has been opened at Kaiser Permanente Northern California since September 2005. There are 15 patients enrolled. All have been evaluable for toxicity and the drug is very well tolerated so far by this population of patients. Out of 15 patients 12 are evaluable for response. Two patients have recently started the protocol therapy and have not met the time point for disease assessment. One patient discontinued the treatment after one infusion due to toxicity (elevated LFTs). One patient completed 11 cycles of Abraxane, while maintaining stable disease on bone scan and achieved a PR by PSA. Ten patients have come off study due to progressive disease based on clinical presentation, rising PSA or signs of radiological progression. There are currently 4 patients actively receiving therapy. Updated results will be presented at the time of ASCO 2007 meeting. No significant financial relationships to disclose.

Eligibility criteria requirements and adherence in advanced prostate cancer trials.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 245-245
Author(s):  
Sarah Wong ◽  
Christopher Sweeney ◽  
Srikala S. Sridhar
Keyword(s):  
Prostate Cancer ◽  
General Population ◽  
Advanced Prostate Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Phase Iii ◽  
Failure Rates ◽  
Eligibility Criteria ◽  
Screen Failure ◽  
Cancer Trials

245 Background: Eligibility criteria for advanced (metastatic and locally advanced) prostate cancer trials vary between trials and are specific to the therapy evaluated, and may not represent the general population. This reduces comparability between studies, generalizability of results, and may contribute to high screen failure rates (~25%). In this study, we aimed to better understand the eligibility criteria across trials and adherence to eligibility criteria. Methods: We compared eligibility criteria between trials and collected baseline demographics to assess for adherence to criteria for 13 phase III advanced prostate cancer trials published from 1999-2016. Results: Disease characteristics, age, performance status, tumor markers, and most hepatic, renal, and hematological criteria were consistent across trials. However, discrepancies in hemoglobin, absolute neutrophil count, glomerular filtration rate (GFR) and bilirubin criteria were observed (Table). Overall, 8/13 trials included patients that did not meet criteria but were analyzed by intent-to-treat. Criteria that were not followed included: hemoglobin and albumin (lower than permitted); while testosterone, serum creatinine, pain scores, and ECOG performance status were higher (more unwell) than permitted. Conclusions: Specific eligibility criteria vary across the trials, and a number of trials accrued ineligible patients. After accounting for drug-specific criteria, greater standardization of and consideration of general population for eligibility criteria is needed to improve homogeneity of trial populations across studies, generalizability of results, and possibly reduce screen failure rates in prostate cancer trials. [Table: see text]

Performance status restriction in phase III cancer clinical trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2059-2059
Author(s):  
Ramez Kouzy ◽  
Joseph Abi Jaoude ◽  
Walker Mainwaring ◽  
Timothy Lin ◽  
Austin B. Miller ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Factors Associated ◽  
Fda Approval ◽  
Ecog Ps ◽  
Patient Accrual

2059 Background: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We sought to characterize trial-related factors associated with the use of eligibility criteria that restrict patients by PS, and analyze patient accrual breakdown by PS. Methods: We searched ClinicalTrials.gov for phase III RCTs between 2003-2018. Randomized multi-arm trials assessing a therapeutic intervention in cancer patients were included. PS data were extracted from corresponding manuscripts. Trials with PS restriction Eastern Cooperative Oncology Group (ECOG) ≤1 were identified. Factors associated with PS restriction were determined, and trial patient accrual was analyzed. Results: Six-hundred trials were included with PS data for 238,213 patients. In total, 527 studies (87.8%) specified an upper PS restriction cutoff as part of their exclusion criteria, and 237 studies (39.5%) had a strict inclusion criterion of patients with ECOG PS ≤1. Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P< 0.001) and lung cancer trials (P < 0.001). Nearly half of trials that led to subsequent FDA approval included strict PS restrictions. Binary logistic regression revealed stable use of restrictive PS eligibility criteria between 2007-2018 (P= 0.789). The vast majority of patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of enrolled patients had a poor PS (ECOG 2 or higher).Trials of hematologic cancers had the largest proportion of patients with ECOG PS ≥2 (8.7%), while lung, breast, gastrointestinal and genitourinary trials all included less than 5% of patients with poor PS (P< 0.001). Only 4.8% of patients enrolled in trials that led to subsequent FDA approval had a poor PS. Conclusions: The use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring, to ensure generalizability of results, while maintaining patient safety.

scholarly journals Recent advances in de-intensification of radiotherapy in elderly cancer patients

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 447
Author(s):  
Isacco Desideri ◽  
Viola Salvestrini ◽  
Lorenzo Livi
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Older Patients ◽  
The Elderly ◽  
Phase Iii ◽  
Elderly Cancer Patients ◽  
Individualized Care ◽  
Whole Breast Radiotherapy

Cancer in the elderly remains an evolving issue and a health challenge. Several improvements in the radiotherapy field allow the delivery of higher doses/fractions with a safe toxicity profile, permitting the reduction of radiation treatment protocols in the elderly. Regarding breast, prostate, and lung cancer, the under-representation of older patients in clinical trials limits the extension of treatment recommendations to elderly patients in routine clinical practice. Among the feasible alternatives to standard whole breast radiotherapy (WBRT) in older patients are shorter courses using higher hypofractionation (HF) and accelerated partial breast irradiation (APBI). The boost continues to be used in women at high risk of local recurrence but is less widely accepted for women at lower risk and patients over 70 years of age. Regarding prostate cancer, there are no published studies with a focus on the elderly. Current management decisions are based on life expectancy and geriatric assessment. Regimens of HF and ultra-HF protocols are feasible strategies for older patients. Several prospective non-randomized studies have documented the safe delivery of ultra-HF for patients with localized prostate cancer, and multiple phase III trials and meta-analyses have confirmed that the HF regimen should be offered with similar acute toxicity regardless of patient age and comorbidity. A recent pooled analysis from two randomized trials comparing surgery to stereotactic body radiation therapy (SBRT) in older adult patients with early stage non-small cell lung cancer did show comparable outcomes between surgery and SBRT. Elderly cancer patients are significantly under-represented in all clinical trials. Thus, the inclusion of older patients in clinical studies should be strongly encouraged to strengthen the evidence base for this age group. We suggest that the creation of oncogeriatric coordination units may promote individualized care protocols, avoid overtreatment with aggressive and unrecommended therapies, and support de-escalating treatment in elderly cancer patients.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

scholarly journals Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1388
Author(s):  
Manlio Mencoboni ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
Paola Taveggia ◽  
Alessia Cavo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria

Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs. We performed a systematic review and a meta-analysis to evaluate the effectiveness and safety of these drugs, and more generally of ICIs, as second-line therapy in NSCLC patients in real world practice. MEDLINE, PubMed, Scopus and Web of Science were searched to include original studies published between January 2015 and April 2020. A total of 32 studies was included in the meta-analysis. The overall radiological response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were 21%, 52%, 3.35 months and 9.98 months, respectively. The results did not change when analysis was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) and age. A unitary increase in the percent of patients with liver and CNS metastases reduced the occurrence of DCR by 7% (p < 0.001) and the median PFS by 2% (p = 0.010), respectively. The meta-analysis showed that the efficacy and safety of immunotherapy in everyday practice is comparable to that in clinical trials.

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