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]

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 Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials

2018 ◽  
Vol 14 (6) ◽  
pp. e357-e367 ◽  
Author(s):  
Fay J. Hlubocky ◽  
Nancy E. Kass ◽  
Debra Roter ◽  
Susan Larson ◽  
Kristen E. Wroblewski ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Informed Consent ◽  
Phase I ◽  
Advanced Cancer ◽  
Interaction Analysis ◽  
Trial Participation ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Advanced Cancer Patients ◽  
Medical Benefits

Purpose: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. Methods: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. Results: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). Conclusion: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.

Comprehension and recall from the informed consent process by phase I healthy volunteers before dose administration

2019 ◽  
Vol 16 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Rami Tadros ◽  
Gillian E Caughey ◽  
Sally Johns ◽  
Sepehr Shakib
Keyword(s):  
Clinical Trials ◽  
Informed Consent ◽  
Phase I ◽  
Healthy Volunteers ◽  
Drug Administration ◽  
Study Drug ◽  
Informed Consent Process ◽  
Consent Process ◽  
Phase I Clinical Trials ◽  
Study Drug Administration

Aims/Background A fundamental part of all clinical trials is informed consent, reflecting the respect for the volunteer’s autonomy. Research participation is voluntary; therefore, certain aspects of the proposed study must be disclosed so that volunteers can make an informed decision. In this study, we aimed to examine the level of comprehension and recall of healthy volunteers from the informed consent process. Methods The study was carried out at a single phase I clinical trials unit. A questionnaire was administered to each volunteer to assess recall of important aspects of the study at the day-1 visit following the informed consent process. The questionnaire contained seven questions regarding study objectives, route, frequency and type of drug administration, adverse effects, number of subjects previously exposed and remuneration. One point was awarded for each correct answer. Results A total of 266 volunteers were administered the questionnaire. The mean total score (±standard deviation) for all volunteers was 4.5 ± 1.1 points out of 7, with a range of 0.8–6.7. For all 10 studies, 91% of volunteers responded correctly when answering about the route of administration, and 90% were able to accurately state the correct payment amount. Only 7% were able to repeat the aims of the study correctly. Conclusion The poor performance of our study volunteers raises concerns about recall of information prior to study drug administration. This has implications for the volunteer’s safety and ability to provide true informed consent. Interventions to improve recall prior to dosing should be undertaken.

scholarly journals Do Patients With Advanced Cancer Have the Ability to Make Informed Decisions for Participation in Phase I Clinical Trials?

2018 ◽  
Vol 36 (24) ◽  
pp. 2483-2491 ◽  
Author(s):  
Fay J. Hlubocky ◽  
Greg A. Sachs ◽  
Eric R. Larson ◽  
Halla S. Nimeiri ◽  
David Cella ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Executive Function ◽  
Phase I ◽  
Advanced Cancer ◽  
Phase I Trials ◽  
Trail Making Test ◽  
Phase I Clinical Trials ◽  
Trail Making

Purpose Patients with advanced cancer (ACPs) participating in phase I clinical trials inadequately understand many elements of informed consent (IC); however, the prevalence and impact of cognitive impairment has not been described. Patients and Methods ACPs enrolled onto phase I trials underwent neuropsychological assessment to evaluate cognitive functioning (CF) covering the following domains: memory (Hopkins Verbal Learning Test), executive functioning (Trail Making Test B), language (Boston Naming Test-Short Version and Controlled Oral Word Association Test), attention (Trail Making Test A and Wechsler Adult Intelligenence Scale-IV Digit Span), comprehension (Wechsler Adult Intelligence Scale-IV), and quality of life (Functional Assessment of Cancer Therapy–Cognitive Function). Structured interviews evaluated IC and decisional capacity. Psychological measures included distress (Hospital Anxiety Depression Scale) and depression (Beck Depression Inventory-II). Results One hundred eighteen ACPs on phase I trials were evaluated, with CF ranging from mild impairment to superior performance. Only 45% of ACPs recalled physician disclosure of the phase I trial purpose. The 50% of ACPs who correctly identified the phase I research purpose had greater CF compared with ACPs who did not, as revealed by the mean T scores for memory (37.2 ± 5.6 v 32.5 ± 5.1, respectively; P = .001), attention (29 ± 2.7 v 26.9 ± 2.4, respectively; P < .001), visual attention (35.2 ± 6.6 v 31.5 ± 6.2, respectively; P = .001), and executive function (38.9 ± 7.5 v 34 ± 7.1, respectively; P < .001). Older ACPs (≥ 60 years) were less likely to recall physician disclosure of phase I purpose than younger ACPs (30% v 70%, respectively; P = .02) and had measurable deficits in total memory (34.2 ± 5.0 v 37.3 ± 5.6, respectively; P = .002), attention (24.5 ± 2.6 v 28 ± 2.8, respectively; P < .001), and executive function (32.8 ± 7.3 v 36.4 ± 7.6, respectively; P = .01). Older ACPs, compared with younger ACPs, also had greater depression scores (10.6 ± 9.2 v 8.1 ± 5.2, respectively; P = .03) and lower quality-of-life scores (152 ± 29.6 v 167 ± 20, respectively; P = .03). After adjustment by age, no psychological or neuropsychological variable was further significantly associated with likelihood of purpose identification. Conclusion CF seems to play a role in ACP recall and comprehension of IC for early-phase clinical trials, especially among older ACPs.

Integration of specialty palliative care in a phase I ovarian cancer population.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 75-75
Author(s):  
Marisa R Moroney ◽  
Breana Hill ◽  
Jeanelle Sheeder ◽  
Jennifer Robinson Diamond ◽  
Melony Avella-Howell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Palliative Care ◽  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Disease Stage ◽  
Phase I Clinical Trials ◽  
Care Services ◽  
Palliative Care Services

75 Background: ASCO guidelines recommend patients with advanced cancer receive early integrated specialty palliative care based on evidence of multiple clinical benefits. To our knowledge, there is no literature evaluating utilization of specialty palliative care in Phase I clinical trial patients, but there is limited data demonstrating underutilization of palliative care services in patients with life-threatening diseases including advanced cancer. Methods: A retrospective review of ovarian cancer patients enrolled in Phase I clinical trials at one institution from 2008 to 2018. Charts were reviewed for patient and disease characteristics including age, disease stage, number of chemotherapy regimens and date of death. Charts were also reviewed to determine if and when patients received specialty palliative care services. Results: A total of 121 patients with ovarian cancer were enrolled in Phase I clinical trials. Median age at time of Phase I enrollment was 59 years (range 33-88). 87% of patients had advanced stage disease: 60% Stage III and 27% Stage IV. Median number of chemotherapy regimens received prior to Phase I enrollment was 5 (range 1-13). Median survival was 311 days (95%CI 225.9-396.1). Of the 121 patients, 4 (3.3%) received specialty palliative care prior to Phase I enrollment, 7 (5.8%) within 30 days after enrollment, and 53 (43.8%) more than 30 days after enrollment. 57 patients (47.1%) never received specialty palliative care. Conclusions: Ovarian cancer patients enrolled in Phase I clinical trials have advanced cancer – defined by ASCO as disease that is late-stage and life limiting with a prognosis less than 24 months – and should therefore receive early integrated specialty palliative care. This study demonstrates that a significant portion of Phase I ovarian cancer patients are either receiving no or late integration of specialty palliative care. Further work needs to focus on increasing early integration of specialty palliative care in this population.

Do Symptoms Matter When Considering Patients for Phase I Clinical Trials? A Pilot Study of Older Adults With Advanced Cancer

2011 ◽  
Vol 28 (7) ◽  
pp. 463-466 ◽  
Author(s):  
Jennifer M. Healy ◽  
Taral Patel ◽  
Shuko Lee ◽  
Sandra Sanchez-Reilly
Keyword(s):  
Older Adults ◽  
Clinical Trials ◽  
Phase I ◽  
Advanced Cancer ◽  
Poor Prognosis ◽  
Chart Review ◽  
Retrospective Chart Review ◽  
Experimental Treatment ◽  
Pain Scale ◽  
Phase I Clinical Trials

Background: Older adults (OA) with advanced cancer (AC) undergoing phase I clinical trials (PICT) have poor prognosis. There are no studies which describe symptoms experienced by OA. Methods: Retrospective chart review of PICT participants >60 years. OA were compared by age (>65 vs 60-65) and by number of symptoms (>3 vs ≤3). Results: N = 56. Mean age = 67.09; 48.21% female. Median life-expectancy = 5 months (interquartile range = 2-9 months); 80.36% had pain; of those 64% without pain scale. Most did not have interdisciplinary professionals or hospice referrals. Older adults with >3 symptoms had more admissions (37.5% vs 14.29%; P = .0335), complications (46.43% vs 16.07%; P = .0026), and greater decline in functional status (24 participants >3 symptoms vs 8; P = .0173). There were no significant differences comparing OA by age. Conclusions: Older adults enrolled in PICT with more symptoms may sacrifice QOL for experimental treatment.

scholarly journals Outcomes of patients with advanced cancer and KRAS mutations in phase I clinical trials

Oncotarget ◽  
2014 ◽  
Vol 5 (19) ◽  
pp. 8937-8946 ◽  
Author(s):  
Rabih Said ◽  
Yang Ye ◽  
Gerald Steven Falchook ◽  
Filip Janku ◽  
Aung Naing ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Advanced Cancer ◽  
Phase I Clinical Trials ◽  
Kras Mutations

Prospective study of oncogenic mutations in circulating cell-free DNA (cfDNA) using a multiplex sequencing platform for patient (pt) allocation to phase I clinical trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10525-10525 ◽  
Author(s):  
Michael Ong ◽  
Joaquin Mateo ◽  
Lorna Pope ◽  
Amy Mulick Cassidy ◽  
Timothy Anthony Yap ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Prospective Study ◽  
Phase I ◽  
Advanced Cancer ◽  
Dna Analysis ◽  
Clinical Decision Making ◽  
Locally Advanced ◽  
Phase I Clinical Trials ◽  
Oncogenic Mutations ◽  
Mutation Data

10525 Background: Studies suggest that tumoral cfDNA can be isolated from plasma and used as a biomarker. Methods: We conducted a prospective study in adult pts with advanced cancer referred for phase I clinical trials Sep09-Dec10 (A: Pilot Phase n=104) and Jan11-Sep11 (B: Expansion Phase n=176). cfDNA and tumor DNA from formalin-fixed paraffin-embedded (FFPE) tissue were isolated, quantified, and analyzed for 238 mutations in 19 oncogenes by the Sequenom OncoCarta Panel 1.0. Mutation data were used for trial allocation when available. Pt data and outcomes were collected. Statistical inferences used Wilcoxon rank-sum and Pearson’s Chi-squared. Results: 280 pts enrolled including breast (60), colorectal (42), ovarian (37), lung (31), and prostate (20); median age 60yrs [23-81]; 93% ECOG PS 0-1. cfDNA in 95% and FFPE in 60% were analyzed. Median time to cfDNA result, trial allocation and consent were 7 [5-14], 6 and 23 d. Median cancer pt cfDNA concentration (ng/ml) (A: 18 [1-1600]; B: 34 [16-1657]) was higher than 20 healthy volunteers (6 [5-13] A: p=0.0001) and higher in metastatic vs locally advanced cancer (A: 21 vs 4 p=0.0006; B: 42 vs 24 p=0.066). Pts with higher than median [cfDNA] had shorter median survival (MST) than below (A: 217 vs 274 d, HR 1.72 95% CI 1.07-2.65, p=0.025; B: MST not reached yet). Mutations were found in 89 pts (32%), including KRAS (11%), PIK3CA (5%), MET (5%), BRAF (4%), and AKT (2%). cfDNA mutations (57 pts, 21.5%) were mainly found above the median [cfDNA] (A: 41 vs 17% χ2=6.9, p=0.009; B: 24 vs 11% χ2=5.0, p=0.025). Of 155 pts with both cfDNA and FFPE available, 68 had mutations detected: 30 identical in cfDNA and FFPE; 28 in FFPE alone and 10 in cfDNA alone. Overall, 153 pts were treated on a phase I trial; 23 pts had relevant mutation data and received a trial targeting the PI3-Akt-mTOR axis. Conclusions: Higher cfDNA is associated with greater disease burden, worse prognosis, and higher mutation detection rate, suggesting cfDNA is tumorally derived. Moreover, cfDNA can be analyzed for oncogenic mutations in a time-frame suitable for clinical decision making, making it a potentially useful non-invasive adjunct to tumour DNA analysis.

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