Predictors of dose limiting toxicities in phase I clinical trials: The impact of age, comorbidity, and other clinical and non-clinical factors

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 9525-9525 ◽  
Author(s):  
N. K. LoConte ◽  
J. F. Cleary ◽  
J. Bozeman ◽  
G. Wilding ◽  
D. Alberti ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Clinical Factors ◽  
Phase I Clinical Trials ◽  
The Impact

A randomized controlled trial to evaluate the impact of an educational DVD on cancer patients considering participation in a phase I clinical trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6011-6011
Author(s):  
E. L. Strevel ◽  
C. Newman ◽  
G. R. Pond ◽  
M. Maclean ◽  
L. L. Siu
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Controlled Trial ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Randomized Controlled ◽  
Clinic Appointment ◽  
The Mean ◽  
The Impact ◽  
Self Administered Questionnaire

6011 Background: Informed consent for phase I trials is controversial; gaps in patient (pt) knowledge regarding the purpose of these studies are central to this debate. This study assessed the impact of viewing an educational DVD on pt knowledge and satisfaction in cancer pts newly referred to a phase I trials clinic. Methods: Prior to physician (MD) appointment, 49 pts were randomly assigned to view either an educational DVD (n = 22) which provided information about phase I trials, or a placebo DVD (n = 27) which described research achievements by local scientists. Upon completion of DVD viewing, pts completed a self-administered questionnaire addressing their understanding of phase I trials (knowledge) and their satisfaction with the DVD (perception). The interviewing MD (n = 8), who was blinded to the intervention, also rated the pt’s understanding of phase I trials upon completion of the clinic appointment. Results: The mean pt age was 56 and 61% were male. Prior to attending the phase I clinic, most pts (86%) had previously heard of clinical trials, but only 49% were aware of phase I trials. Pts who viewed the educational DVD were less likely to believe that the goal of phase I trials is to determine the efficacy of a new drug (p = 0.019), more likely to correctly assess that drugs undergoing phase I evaluations have not been thoroughly studied in humans (p = 0.003), and less likely to believe that phase I drugs have proven activity against human cancers (p = 0.008). More pts who viewed the educational DVD than the placebo DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), believed that they had a good knowledge of phase I trials (p = 0.031), felt that the DVD helped them decide whether to enter a phase I trial (p = 0.011), and perceived that they would have more questions for their physicians as a result of watching the DVD (p = 0.017). No statistically significant differences in MD satisfaction was observed. Conclusions: Exposure to an educational DVD increased both objective measures of pt knowledge as well as pt satisfaction regarding participation in phase I clinical trials. The educational DVD did not significantly impact MD perception of pt understanding. No significant financial relationships to disclose.

Impact of Quality of Life on Patient Expectations Regarding Phase I Clinical Trials

2000 ◽  
Vol 18 (2) ◽  
pp. 421-421 ◽  
Author(s):  
Jonathan D. Cheng ◽  
James Hitt ◽  
Bogda Koczwara ◽  
Kevin A. Schulman ◽  
Caroline B. Burnett ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Phase I ◽  
Patient Expectations ◽  
Experimental Therapy ◽  
Phase I Clinical Trials ◽  
Potential Benefits ◽  
Research Nurses ◽  
The Impact

PURPOSE: Quality of life (QOL) is increasingly recognized as a critical cancer-treatment outcome measure, but little is known about the impact of QOL on the patient decision-making process. A pilot study was conducted in an effort to (1) measure the expectations of patients, physicians, and research nurses regarding the potential benefits and toxicities from experimental and standard therapies, and (2) determine the relationship of QOL to patient perceptions regarding treatment options. METHODS: Thirty cancer patients enrolling in phase I clinical trials, their physicians, and their research nurses were administered questionnaires that assessed demographics, QOL, and treatment expectations. RESULTS: Compared with their physicians, patients overestimated potential benefits and toxicities from experimental therapy (mean expected benefit, 59.8% v 23.8%, P < .01; mean expected toxicity, 29.8% v 16.0%, P < .01). Patients estimated a greater potential for benefit (59.8% v 36.8%, P < .01) and less potential for toxicity (29.8% v 45.6%, P = .01) for experimental therapy, compared with standard therapy. Short Form- 36 general health perception correlated with patient perception of potential benefit from experimental therapy (r = .48, P = .01). CONCLUSION: Participants in phase I clinical trial have high expectations regarding the success of experimental therapy and discount potential toxicity. Patient QOL may affect the expectation of benefit from experimental therapy and, ultimately, treatment choice. Understanding the interactions between QOL and patient expectations may guide the development of improved strategies to present appropriate information to patients considering early-phase clinical trials.

scholarly journals Isotonic Design for Phase I Clinical Trials: Can We Improve Further?

2019 ◽  
Vol 48 (5) ◽  
pp. 34-44
Author(s):  
M. Iftakhar Alam ◽  
Jafrin Sultana
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Appreciable Effect ◽  
Cohort Size ◽  
Phase I Clinical Trials ◽  
Toxic Dose ◽  
Number Of Patients ◽  
Monotonicity Assumption ◽  
Toxicity Relationship ◽  
The Impact

One of the most challenging tasks in clinical trials is finding the maximum tolerated dose (MTD) to be tested in the next phase. An assurance for the safety of the patients and recommendation of a suitable dose for phase II are the main objectives of a phase I trial. The MTD can be identified through various approaches. A non-parametric approach, known as the isotonic design, has been explored in our study. The design relies on the monotonicity assumption of the dose-toxicity relationship. Usually the number of patients in a trial have an impact on the adequacy of dose recommendation. This paper is a humble attempt to see the impact of cohort size and total cohorts on the isotonic design. It investigates the possibility of improving the current algorithm of the isotonic design for escalation and de-escalation. Also, the paper proposes a stopping rule to avoid any severely toxic dose as the MTD. The simulation study shows that along with total cohort, cohort size also has an appreciable effect on the MTD selection. The proposed modification of the algorithm has also been found to work satisfactorily in majority of the cases.

Integration of palliative care for patients with solid tumors on phase I clinical trials.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 138-138 ◽  
Author(s):  
Betty R. Ferrell ◽  
Vincent M. Chung ◽  
Marianna Koczywas ◽  
Anna Cathy Williams ◽  
Arti Hurria ◽  
...  
Keyword(s):  
Palliative Care ◽  
Clinical Trials ◽  
Phase I ◽  
Symptom Burden ◽  
Care Planning ◽  
Phase I Clinical Trials ◽  
Advanced Directives ◽  
Care Services ◽  
Advance Care ◽  
The Impact

138 Background: Cancer patients receiving Phase I clinical trials are a population with advanced disease, high symptom burden, and with multiple QOL concerns including use of advance directives. Methods: An NCI funded R01 is currently in progress (2014-2019) as a randomized clinical trial to test a palliative care intervention (PCI) in this population. The PCI includes comprehensive patient assessment, goals of care communication, interdisciplinary care planning and patient teaching. Aims and hypotheses test the impact of the PCI on symptoms, QOL, resource use, spirituality and distress. Outcomes for the study (N = 400) will be conducted at the conclusion of the RCT. This paper reports preliminary baseline data of the first 100 subjects accrued. Results: Subjects mean age was 59 years and 59% were female, similar to prior trials. Forty eight percent (48%) were ethnic minorities, higher than prior trials (3% non-white, Finlay E, 2014; 9%, Parsons JA, et al. PLoS One 2012) with colon (22%) and lung (21%) cancers as dominant. Patients had a mean of 2 comorbidities (range 0-8) and 40% of the patients are > 65 years of age. The most common symptoms reported by PRO-CTCAE (1 = least to 5 = most concern) were sexuality (4.2), fatigue (2.9), pain (2.6) and anxiety (2.5). Psychological Distress Thermometer, (0 - least to 10 = most distress) mean score was 4. FACIT spiritual concerns (1 = least to 5 = most concerning) identified greatest concerns of illness strengthening faith (2.0), strength from faith (2.0) and sense of harmony (2.6). There was limited use of supportive care services, PC consultation, or advanced directives. Conclusions: The population of Phase I trial patients is an important group for palliative care integration with major unmet needs in symptom management and advance care planning.

scholarly journals Cancer-Related Internet Use and Online Social Networking Among Patients in an Early-Phase Clinical Trials Clinic at a Comprehensive Cancer Center

2018 ◽  
pp. 1-14 ◽  
Author(s):  
Goldy C. George ◽  
Adrianna Buford ◽  
Kenneth Hess ◽  
Sarina A. Piha-Paul ◽  
Ralph Zinner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Internet Use ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Cancer Information ◽  
The Internet ◽  
Phase I Clinical Trials ◽  
Experimental Drugs ◽  
The Impact

Purpose We examined patterns, correlates, and the impact of cancer-related Internet use among patients with advanced cancer in a phase I clinical trials clinic for molecularly targeted oncologic agents. Methods An anonymous questionnaire on Internet use for cancer-related purposes that incorporated input from phase I clinical trial oncologists and patients was self-administered by patients age ≥ 18 years in a phase I clinic. Multivariable modeling was used. Data were analyzed for the overall sample and by generation, which was defined by year of birth. Results Of 291 patients (52% women, 82% non-Hispanic white, 50% age ≤ 60 years), 62% were cancer-related Internet users (CIUs). Cancer-related Internet use was associated with an income of ≥ $60,000 (odds ratio, 2.42; P = .004). CIUs used the Internet to learn about their cancer (85%), treatment adverse effects (65%), clinical trials (52%), new alternative treatments (42%), and symptom management (41%). CIUs most frequently used the hospital Web site (70%) to learn about clinical trials, followed by ClinicalTrials.gov (42%) and search engines (41%). The emotional impact of Internet-derived cancer information on CIUs varied—56% felt empowered, 34% anxious, 29% relieved, and 17% confused. Cancer-related Internet information made 51% of patients from the Millennial (born after 1990) and Generation X/Y (born 1965 to 1990) CIU populations anxious compared with < 29% of CIUs from older generations (born 1964 and before). Most CIUs desired more online information about new experimental drugs (91%) and US Food and Drug Administration–approved drugs for cancer (72%). Conclusion As most phase I patients use the Internet for cancer-related purposes, the Internet overall and hospital Web sites should provide more extensive, pertinent, and helpful information on clinical trials and cancer treatment to phase I patients.

Validation of toxicity burden score for use in phase I clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2514-2514
Author(s):  
S. M. Lee ◽  
D. Hershman ◽  
P. Martin ◽  
J. Leonard ◽  
K. Cheung
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Regression Model ◽  
Mixed Effects ◽  
Training Data ◽  
Phase I Clinical Trials ◽  
Validation Data ◽  
Severity Scores ◽  
Grade 3 ◽  
The Impact

2514 Background: In phase I clinical trials, dose limiting toxicity (DLT) is defined as a binary outcome (DLT Yes/No). Concerns have been raised since this does not account for multiple non-DLTs that have a cumulative effect on drug tolerability and do not differentiate the severity of DLTs. Having a continuous toxicity burden score (TBS) as an outcome may provide more information regarding toxicity. We propose a new method for obtaining TBS. Methods: We illustrate the method using a phase I trial in lymphoma. The two main toxicities related to the experimental drug were low platelets and neuropathy with DLT defined as platelet count < 10,000/mm3 or grade 3 neuropathy. Three oncologists were asked to assign severity scores for the two main toxicities by assigning scores based on their impression of the impact of the toxicity on the patient and keeping in mind that DLT should be assigned a score of 1 and no toxicity should be assigned a score of 0. They were then given data from 25 patients along with their observed toxicities and the respective NCI toxicity grades and were asked to assign TBS to each patient. A mixed effects regression model was fit to the data. To validate the model, two of the oncologists assigned TBS to an additional list of 17 patients. Assuming the estimated TBS to be a rating, the three ratings (two oncologists and the estimated TBS) were compared using a mixed effects regression model. Results: The significant predictors of TBS are listed in the Table . Since no patient in the training data experienced grade 3 low- platelet and grade 4 neuropathy, model coefficients for these were not obtained. In the validation data, the TBS among the oncologists and the estimated TBS obtained using the fitted model were not different (P=0.18). Conclusions: A fitted model can be used to obtain TBS from maximal NCI toxicity grades suggesting the feasibility of using a continuous outcome such as TBS in dose finding studies. [Table: see text] No significant financial relationships to disclose.

scholarly journals Analysis of Impact of Post-Treatment Biopsies in Phase I Clinical Trials

2016 ◽  
Vol 34 (4) ◽  
pp. 369-374 ◽  
Author(s):  
Randy F. Sweis ◽  
Michael W. Drazer ◽  
Mark J. Ratain
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Phase I ◽  
Maximum Tolerated Dose ◽  
Phase I Clinical Trials ◽  
Early Phase Clinical Trials ◽  
Pharmacodynamic Biomarkers ◽  
Tumor Biopsies ◽  
Phase Ii And Iii ◽  
The Impact

Purpose The use of biopsy-derived pharmacodynamic biomarkers is increasing in early-phase clinical trials. It remains unknown whether drug development is accelerated or enhanced by their use. We examined the impact of biopsy-derived pharmacodynamic biomarkers on subsequent drug development through a comprehensive analysis of phase I oncology studies from 2003 to 2010 and subsequent publications citing the original trials. Methods We conducted a search to identify and examine publications of phase I oncology studies including the use of biopsy-derived pharmacodynamic biomarkers between 2003 and 2010. Characteristics of those studies were extracted and analyzed, along with outcomes from the biomarker data. We then compiled and reviewed publications of subsequent phase II and III trials citing the original phase I biomarker studies to determine the impact on drug development. Results We identified 4,840 phase I oncology publications between 2003 and 2010. Seventy-two studies included a biopsy-derived pharmacodynamic biomarker. The proportion of biomarker studies including nondiagnostic biopsies increased over time (P = .002). A minimum of 1,873 tumor biopsies were documented in the 72 studies, 12 of which reported a statistically significant biomarker result. Thirty-three percent of studies (n = 24) were referenced by subsequent publications specifically with regard to the biomarkers. Only five positive biomarker studies were cited subsequently, and maximum tolerated dose was used for subsequent drug development in all cases. Conclusion Despite their increased use, the impact of biopsy-derived pharmacodynamic biomarkers in phase I oncology studies on subsequent drug development remains uncertain. No impact on subsequent dose or schedule was demonstrated. This issue requires further evaluation, given the risk and cost of such studies.

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