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.

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.

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

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.

Outcomes of patients ≥ 65 yrs with advanced cancer treated on phase I clinical trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9544-9544
Author(s):  
Ishwaria Mohan Subbiah ◽  
Jennifer J. Wheler ◽  
Kenneth R. Hess ◽  
David S. Hong ◽  
Siqing Fu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Advanced Cancer ◽  
Therapeutic Option ◽  
Study Drug ◽  
Clinic Visit ◽  
Phase I Clinical Trials ◽  
Disease Biology ◽  
Grade 3 ◽  
Ecog Ps

9544 Background: Older patients with cancer are underrepresented in clinical trials; their disease biology and comorbidities may impact the decision to consider a clinical trial. Here we systematically analyze outcomes of elderly pts treated on phase I clinical trials. Methods: The characteristics, toxicity, survival, and response of pts with advanced cancer treated on phase I clinical trials from 1/04 – 12/09 were studied. Results: Overall,347 of 1,182 pts (29%) were >65 yrs old. The Table lists pt characteristics by treatment regimen. 251 pts received a targeted agent, of which 241 (96%) received an investigational, non-FDA approved drug. Of 347 pts, 3 (1%) had a CR, 15 (4%) a PR, 127 (37%) SD, of which 43 (12%) had SD ≥ 6mos. Of 347 pts, 194 (56%) had >1 drug-related toxicity, of which 89 (26%) had a Grade 3-4 toxicity, most often hematologic; 72% of toxicities on targeted therapies were Grade 1-2. Six pts had a DLT; there was one death (<0.01%) “possibly” attributed to the study drug. Median OS from 1st phase I Clinic visit was 8.8mos (95% CI, 7.8-10.6). Median TTF on 1st phase I trial was 1.9mos (95% CI, 1.8-2.1). Multivariate analyses demonstrated that ECOG PS 2-3 (vs. 01) (p <0.001) and liver mets (vs. no liver mets) (p <0.01) were independent factors predicting shorter TTF and OS. Conclusions: Our results suggest that phase I clinical trials are well tolerated and offer a reasonable therapeutic option for pts > 65 yrs. [Table: see text]

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.

Prognostic and predictive factors associated with ipilimumab related adverse events: A retrospective analysis of 11 NCI sponsored ipilimumab phase I clinical trials.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 86-86
Author(s):  
Aman Chauhan ◽  
Tanvir Kabir ◽  
Jianrong Wu ◽  
Jing Wei ◽  
Charles Kunos
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Lymphocyte Count ◽  
Response To Therapy ◽  
High Grade ◽  
Phase I Clinical Trials ◽  
Duration Of Treatment ◽  
Radiological Response ◽  
Grade 3 ◽  
Ecog Ps

86 Background: We review factors affecting ipilimumab (ipi) associated toxicity in various NCI sponsored phase I clinical trials. Methods: NCI database for NCI sponsored phase I clinical trials evaluating ipilimumab was queried for adverse effects, radiological response data, lymphocyte counts, LDH, albumin, ECOG performance status, duration of treatment and diagnosis. Only treatment related AEs were analyzed. Events repeating across consecutive cycles were treated as a single event. Duration of treatment was calculated starting from cycle 1 day 1 of the treatment. IRB approval from NCI was obtained prior to the study. Results: Data from 373 patients from 11 phase I ipilimumab clinical trials were available for analysis. Median age of the study cohort was 55 years. 68%(n = 235) were males. Number of grade 3 and 4 AEs were associated with better radiological response. Mean grade 3 and 4 AEs in CR+PR cohort was 1.167 vs 0.645 in non-responder cohort (p = 0.001). No significant differences in low or high grade AEs were noticed in study cohorts differentiated based on ECOG PS (0 vs 1/2). ECOG PS 3/4 were not included in clinical trials. Pretreatment lymphocyte count, LDH or albumin was not predictive of increased ipilimumab associated toxicity. Ipilumumab associated grade 3 and 4 toxicity was directly associated with the number of concurrently used study agents. Mean grade 3 and 4 AEs were as follows in following cohorts: ipi alone; 0.631 vs ipi+ 1 drug; 0.877 vs ipi+ 2 drugs; 1.408 (p < 0.0136). Number of low grade (grade 1 and 2) toxicity was associated with duration of treatment. r = 0.456 (p < 0.0001). Number of high grade (grade 3 and 4) toxicity was not associated with duration of treatment with ipilimumab. r = 0.032 (p = 0.546). Conclusions: Ipilimumab associated grade 3 and 4 toxicity predicts response to therapy and is associated with higher CR/PR. ECOG PS, pretreatment lymphocyte count, LDH and albumin levels are not associated with ipilimumab toxicity. Lastly, addition of antitumor agents to ipilimumab has potential to cause a significant increase in serious AE’s.

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.

Do elderly patients benefit from enrollment in phase I clinical trials?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Wai Meng David Tai ◽  
Cindy Lim ◽  
Aziah Ahmad ◽  
Whee Sze Ong ◽  
SuPin Choo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Clinical Characteristics ◽  
Phase 1 ◽  
Prognostic Score ◽  
Progression Free Survival ◽  
Phase I Clinical Trials ◽  
Lung Cancers ◽  
Significant Difference ◽  
Grade 3

9509 Background: Despite the significant burden of cancer in the older population, their outcomes in the context of phase I studies have been poorly studied. We evaluated the clinical characteristics and outcomes of elderly pts enrolled in phase 1 clinical trials in our centre and evaluate the performance of Royal Marsden Hospital (RMH) prognostic score (albumin, LDH, no of met sites) in this pt population. Methods: 296 consecutive pts who were treated in 20 phase 1 trials from 2005-2012 in our unit were analysed. Clinical characteristics and outcomes between young pts (<65, n=202) and older pts (≥65, n=94) were compared. Results: The median age of the older pts was 69 (65-84), 71% were males. 51% of the pts received chemotherapy based treatment with or w/out biological agents. 61% of the pts had lung cancers and 32% had gastrointestinal cancers. 52% of pts had ≥2 co-morbidities. After median follow up of 7.5 mths (0.36-50.6 mths), the median progression free survival (PFS) and overall survival (OS) were 5.8 and 8.8 mths respectively. Although elderly pts had more co-morbidities and lower albumin levels at baseline, there was no significant difference in survival (8.8 vs 9.9 mths), p=0.68) compared to younger pts. The prognostic factors for OS identified in multivariate analysis were prior lines of chemotherapy (0-2 vs ≥3), baseline sodium levels (≥135 vs <135mmol/L) and platelet levels (≤400 vs >400×10⁹). We developed a risk nomogram based on the factors identified prognostic of OS with concordance(c)-index of 0.65. RMH score (2-3 vs 0-1) predicted for OS with hazard ratio of 2.1, p=0.03 and c- index of 0.63. 26% of elderly pts experienced grade 3/4 toxicities in the first cycle of treatment. Common grade 3/4 toxicities were dermatological (25%), haematological (17%) and gastrointestinal (13%). Both age of pts (p=0.70) and dose levels (p=0.18) did not have any bearing on occurrence of grade 3/4 toxicities. Conclusions: Elderly pts (≥65) enrolled into phase 1 clinical trials had similar survival outcomes and toxicity profiles compared to younger pts. Risk scoring models to aid patient selection need further clarification in this population.

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