Approach and Feasibility of Patient-Reported Outcomes (PROs) in a Phase III Clinical Trial for Advanced Stage Classical Hodgkin Lymphoma (cHL) in Children and Adolescents

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3583-3583 ◽  
Author(s):  
Tara O Henderson ◽  
Sharon M Castellino ◽  
Frank G Keller ◽  
Kara M. Kelly ◽  
Rachael Curtis ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Healthcare Utilization ◽  
Patient Reported Outcomes ◽  
Parent Report ◽  
Phase Iii ◽  
Classical Hodgkin Lymphoma ◽  
Patient Reported

Abstract Introduction: Given the high cure rates in classical Hodgkin lymphoma (cHL) with conventional therapy, careful consideration of the economics of newer agents should be considered. We describe the feasibility of embedding Patient-Reported Outcomes (PROs) for chemotherapy-induced peripheral neuropathy (CIPN) and cost effectiveness (CEA) in a randomized, multi-institutional Phase III study [NCT02166463; Children's Oncology Group (COG) AHOD1331], evaluating the efficacy of the novel agent, Brentuximab vedotin, for advanced cHL in children and adolescents. Methods: Recruitment for PROs of interest is targeted for 250 of the planned 600 trial participants. Participation in the trial includes prospective collection of patient- and parent proxy-reported outcomes. CIPN is evaluated with the 11-item FACT-GOG-NTX and paired with the 9-item CHRIs-Global to serially evaluate health-related quality of life (HRQL) consequences of CIPN from initial diagnosis to 12 months off therapy. For CEA, US-based participants are queried from diagnosis through 36 months off therapy with the 4-item Stanford Healthcare Utilization Questionnaire (parent-report), the Health Utilities Index (HUI) 2/3, and the 23-item Caregiver Work Limitations Questionnaire (parent-report) as a measure of productivity loss. A study-designated research assistant is charged with contacting site personnel at study entry and at each scheduled assessment. All data are uploaded into a web-based relational database for future analysis. Units of healthcare utilization from the Stanford Healthcare Utilization measure and adverse events (AE) requiring hospitalization will be monetized with unit costs from US-based administrative databases, including the US National Inpatient Sample (NIS) and Kids' Inpatient Database (KID), Massachusetts All-Payer Claims Database (APCD) and Medicare, based on site of care and diagnostic and/or procedure codes. Data on severe AE from the two predecessor trials (COG AHOD 0031 and AHOD 0831) will be monetized as a training exercise. Total costs will be calculated by study arm and will include monetization of significant adverse events and health care utilization and will be expressed as cost per quality-adjusted life year derived from the HUI. Results: The clinical trial, activated in March 2015, has enrolled 161 participants; accrual is ongoing at 172 participating institutions. 156 participants (>95%) have completed the baseline CIPN and CEA measures. Among participants who have completed the baseline CIPN and CEA assessments, 90% have completed subsequent measures. Monetization of significant adverse events and utilization is in progress. Conclusion: We demonstrate a feasible approach evidenced by high completion rates of assessments for prospective evaluation of CIPN, HRQL, and healthcare utilization in a multi-institutional trial of children with advanced HL. Our experience serves as a proof of principle to cooperative groups regarding the resources and the feasibility of incorporating necessary PRO and health utilization outcomes into Phase III clinical trials as a component of cancer care delivery research. Disclosures Henderson: Seattle Genetics: Research Funding.

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma

2019 ◽  
Vol 60 (11) ◽  
pp. 2705-2711 ◽  
Author(s):  
Bastian von Tresckow ◽  
Michelle Fanale ◽  
Kirit M. Ardeshna ◽  
Robert Chen ◽  
Julia Meissner ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Patient Reported Outcomes ◽  
Phase 2 ◽  
Classical Hodgkin Lymphoma ◽  
Phase 2 Study ◽  
Patient Reported

A pilot study of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in a phase I clinical trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6587-6587 ◽  
Author(s):  
Rui Qin ◽  
Amylou C. Dueck ◽  
Daniel Satele ◽  
Julian R. Molina ◽  
Charles Erlichman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Pilot Study ◽  
Adverse Events ◽  
Phase I ◽  
Patient Reported Outcomes ◽  
Point Of View ◽  
Phase I Clinical Trial ◽  
Phase I Clinical Trials ◽  
Patient Reported

6587 Background: Recently the Patient-Reported Outcomes version of the CTCAE was developed to augment clinically graded adverse events with information reported directly by patients on clinical trials (Basch, 2009). The validation and potential application of PRO-CTCAE in phase I clinical trials are of great interest as toxicity is the primary endpoint. Methods: Selected PRO-CTCAE items (21 items measuring 12 symptomatic adverse events) corresponding to the major adverse events required to be graded clinically were collected in an ongoing phase I clinical trial of weekly cilengitide and paclitaxel in patients with advanced solid malignancies (NCT01276496). PRO-CTCAE was administered in a paper booklet by a clinical research associate prior to treatment on days 1, 8 and 15 of their regular visits. These PRO-CTCAE items were summarized descriptively in comparison to clinician-assessed CTCAE ver 4.0 (NCI, 2009) during the first cycle. As a pilot study to assess feasibility of PRO-CTCAE in phase I trials, PRO-CTCAE was not intended for determination of dose-limiting toxicity. Results: Twelve patients were accrued to two separate doses of cilengitide and paclitaxel. The median age was 56 (range 36—67) and half of patients were female. All patients had an ECOG performance score <= 1. Over 90% of patients had received prior surgery and chemotherapy. All but one patient completed weekly PRO-CTCAE during the first cycle, the only patient refused to complete weeks 2 and 3 did not give a reason. PRO-CTCAE captured most of the symptomatic adverse events reflected in clinician-assessed CTCAE. Some symptomatic adverse events were not reported clinically by CTCAE but were reported by patients by PRO-CTCAE. Overall, PRO-CTCAE items indicated slightly more severe degree of symptoms experienced by patients than those reported in CTCAE. Conclusions: This is the first study that PRO-CTCAE items were integrated within regular study visits in a phase I trial. The administration of PRO-CTCAE has been proved feasible and fruitful, providing consistent and enhanced symptomatic toxicity from the patient point of view. The addition of PRO-CTCAE did not significantly increase patient burden. Clinical trial information: NCT01276496.

Gls-010, a novel anti-PD-1 mAb in Chinese patients with relapsed or refractory classical Hodgkin lymphoma: Preliminary impressive result of a phase II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8033-8033
Author(s):  
Yuqin Song ◽  
Jun Zhu ◽  
Ningjing Lin ◽  
Mingzhi Zhang ◽  
Hai Bai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Genetic Alterations ◽  
Phase Ii Clinical Trial ◽  
Chinese Patients ◽  
Favorable Result ◽  
Classical Hodgkin Lymphoma ◽  
Impressive Result

8033 Background: classical Hodgkin lymphoma (cHL) are characterized by genetic alterations at the 9p24·1 locus and PD-L1 ligand overexpression. GLS-010 is a novel fully human anti-PD-1 mAb and exhibited favorable result in previous Phase I study. This multi-center, single-arm Phase II clinical trial is aimed to further evaluate the safety and efficacy profile of GLS-010 in Chinese patients (pts) with relapsed or refractory cHL. Methods: All pts enrolled received GLS-010 240mg every 2 weeks until disease progression, death, unacceptable toxicity or withdraw from the study. The primary endpoint was objective response rate (ORR) by independent review committee (IRC) per Lugona 2014. Adverse events (AEs) were graded by NCI CTCAE v4.03. Results: 85 pts with relapsed or refractory cHL who had received at least 2 lines of prior systemic chemotherapies were enrolled and treated. As of August 2 2019, data cutoff, pts received a median of 8 treatment cycles (1 cycle include 2 injections), with 12 pts discontinued and 73 pts were still in treatment. At a median follow-up of 6.57 months, an ORR was reported in 78 of 85 patients (91.76%, 95%CI, 83.77-96.62), by an IRC assessment, including 30(35.3%) pts with a complete response (CR) and 48 pts (56.5%) with a partial response (PR). Median duration of response (DoR) and progression free survival (PFS) were not reached yet. Treatment-related adverse events (TRAEs) of any grade occurred in 77 (90.6%) of 85 patients, most of which were Grade 1-2.The most common TRAEs were fever (26/85, 30.6%), neutrophil count decreased (16/85, 18.82%), white blood cell count decreased (15/85, 17.65%). ≥ Grade 3 TRAEs occurred in 23 (27.06%) pts, most commonly, hepatic function abnormal (5/85, 5.88%), hyperuricaemia (4/85, 4.71%). Conclusions: GLS-010 showed impressive anti-tumor activity (ORR = 91.96%) and manageable safety profile in Chinese patients with relapsed or refractory cHL, which could be a new safe and effective treatment option in this setting. Clinical trial information: NCT03655483 .

Randomized double-blind, placebo-controlled study of topical diclofenac in prevention of hand-foot syndrome in patients receiving capecitabine.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS12135-TPS12135
Author(s):  
Atul Batra ◽  
Akhil P. Santosh ◽  
Raja Pramanik ◽  
Ajay Gogia ◽  
R. M. Pandey ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Patient Reported ◽  
Hand Foot Syndrome ◽  
Cox 2 ◽  
Topical Diclofenac

TPS12135 Background: The pathophysiology of capecitabine induced hand-foot syndrome (HFS) includes activation of cyclooxygenase (COX)-2, leading to an upregulation of the inflammatory cascade. Prophylaxis with oral celecoxib was previously reported to be associated with a significantly lower frequency of HFS (grade 1 [29.0% vs. 72.0%, p < 0.001] and grade 2 [11.8% vs. 30.0%, p=0.024]) (1). The findings were confirmed in a phase III trial (2). However, the associated systemic adverse events limit routine prophylactic use. Till date, no clinical trials have assessed the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in preventing HFS. Methods: In this investigator-initiated randomised phase III double-blind, placebo controlled, parallel group trial, a total of 264 patients with any stage breast or gastrointestinal cancer planned to receive capecitabine as a single agent or in combination with other chemotherapy will be randomised (1:1) to 1% topical diclofenac or placebo (base for 1% topical diclofenac) arm at a single tertiary care cancer centre in India. Randomization will be done by stratified (male vs female, and capecitabine mono therapy vs combination) permuted block method using a computer generated random sequence and allocation concealment will be done by using sealed opaque envelopes. In both the arms, patients will be asked to apply 1 fingertip unit (FTU) of topical medication on both surfaces of bilateral hands twice daily for a total duration of 12 weeks or till development of grade 2 or higher HFS, whichever is earlier. The primary objective is to compare the effect of topical diclofenac with placebo in preventing clinically significant HFS (incidence of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 2 or higher HFS). The secondary objectives include comparison of topical diclofenac with placebo on (i) incidence of NCI CTCv5.0 all grade HFS, (ii) time to develop grade ≥2 HFS from start of capecitabine, (iii) patient-reported outcomes using HFS-14 questionnaire (iv) adherence with topical application using self-reported adherence diary, (v) capecitabine dose reductions, delays and cessation due to HFS and (vi) safety profile (NCICTCv5.0). The tertiary correlative endpoint is to correlate the occurrence and severity of HFS with serum COX-2 levels and polymorphism of dihydropyrimidine dehydrogenase (DPPD) enzyme. The trial is registered at the Clinical Trial Registry of India (CTRI/2021/01/030592). Till date, we have enrolled 12/264 patients. (1) Zhang RX et al. J Cancer Res Clin Oncol. 2011;137(6):953-957. (2) Zhang RX et al. Annals of oncology. 2012;23(5):1348-1353. Clinical trial information: CTRI/2021/01/030592.

Feasibility, Reliability, and Value of Remote Video-Based Trial Visits in Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1779-1786
Author(s):  
Christopher G. Tarolli ◽  
Kelly Andrzejewski ◽  
Grace A. Zimmerman ◽  
Michael Bull ◽  
Steven Goldenthal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Patient Reported Outcomes ◽  
Phase Iii ◽  
Moderate Correlation ◽  
Excellent Correlation ◽  
Phase Iii Clinical Trial ◽  
Patient Reported ◽  
One Year

Background: There is rising interest in remote clinical trial assessments, particularly in the setting of the COVID-19 pandemic. Objective: To demonstrate the feasibility, reliability, and value of remote visits in a phase III clinical trial of individuals with Parkinson’s disease. Methods: We invited individuals with Parkinson’s disease enrolled in a phase III clinical trial (STEADY-PD III) to enroll in a sub-study of remote video-based visits. Participants completed three remote visits over one year within four weeks of an in-person visit and completed assessments performed during the remote visit. We evaluated the ability to complete scheduled assessments remotely; agreement between remote and in-person outcome measures; and opinions of remote visits. Results: We enrolled 40 participants (mean (SD) age 64.3 (10.4), 29% women), and 38 (95%) completed all remote visits. There was excellent correlation (ICC 0.81–0.87) between remote and in-person patient-reported outcomes, and moderate correlation (ICC 0.43–0.51) between remote and in-person motor assessments. On average, remote visits took around one quarter of the time of in-person visits (54 vs 190 minutes). Nearly all participants liked remote visits, and three-quarters said they would be more likely to participate in future trials if some visits could be conducted remotely. Conclusion: Remote visits are feasible and reliable in a phase III clinical trial of individuals with early, untreated Parkinson’s disease. These visits are shorter, reduce participant burden, and enable safe conduct of research visits, which is especially important in the COVID-19 pandemic.

scholarly journals Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 103
Author(s):  
Heather S. L. Jim ◽  
Sarah L. Eisel ◽  
Aasha I. Hoogland ◽  
Sandra Shaw ◽  
Jennifer C. King ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Cancer Registry ◽  
Patient Reported Outcomes ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Reported

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have reported on patient-reported outcomes (PROs) outside the context of a clinical trial. The goal of the current study was to assess PROs in participants of a lung cancer registry who had been treated with an ICI. Patients participating in the GO2 Foundation’s Lung Cancer Registry who reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited to participate in a survey about their experiences during treatment. Quality of life was evaluated using the Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverse events were evaluated using an item bank generated for ICIs. Internationally, 226 patients (mean age 61, 75% female) participated. Patients reported worse quality of life at the time of assessment than U.S. population and cancer normative samples. The most common moderate to severe adverse events during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Due to toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization. This study is among the first to our knowledge to report on PROs of ICIs outside the context of a clinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials.

scholarly journals The Effect of Collaborative Reviews of Electronic Patient-Reported Outcomes on the Congruence of Patient- and Clinician-Reported Toxicity in Cancer Patients Receiving Systemic Therapy: Prospective, Multicenter, Observational Clinical Trial (Preprint)

2021 ◽  
Author(s):  
Andreas Trojan ◽  
Nicolas Leuthold ◽  
Christoph Thomssen ◽  
Achim Rody ◽  
Thomas Winder ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Adverse Events ◽  
Cancer Patients ◽  
Systemic Therapy ◽  
Patient Reported Outcomes ◽  
Patient Reported Outcome ◽  
Primary Objective ◽  
Patient Reported ◽  
Level Of Agreement

BACKGROUND Electronic patient-reported outcomes (ePRO) are a relatively novel form of data and have the potential to improve clinical practice for cancer patients. In this prospective, multicenter, observational clinical trial, efforts were made to demonstrate the reliability of patient-reported symptoms. OBJECTIVE The primary objective of this study was to assess the level of agreement κ between symptom ratings by physicians and patients via a shared review process in order to determine the future reliability and utility of self-reported electronic symptom monitoring. METHODS Patients receiving systemic therapy in a (neo-)adjuvant or noncurative intention setting captured ePRO for 52 symptoms over an observational period of 90 days. At 3-week intervals, randomly selected symptoms were reviewed between the patient and physician for congruency on severity of the grading of adverse events according to the Common Terminology Criteria of Adverse Events (CTCAE). The patient-physician agreement for the symptom review was assessed via Cohen kappa (κ), through which the interrater reliability was calculated. Chi-square tests were used to determine whether the patient-reported outcome was different among symptoms, types of cancer, demographics, and physicians’ experience. RESULTS Among the 181 patients (158 women and 23 men; median age 54.4 years), there was a fair scoring agreement (κ=0.24; 95% CI 0.16-0.33) for symptoms that were entered 2 to 4 weeks before the intended review (first rating) and a moderate agreement (κ=0.41; 95% CI 0.34-0.48) for symptoms that were entered within 1 week of the intended review (second rating). However, the level of agreement increased from moderate (first rating, κ=0.43) to substantial (second rating, κ=0.68) for common symptoms of pain, fever, diarrhea, obstipation, nausea, vomiting, and stomatitis. Similar congruency levels of ratings were found for the most frequently entered symptoms (first rating: κ=0.42; second rating: κ=0.65). The symptom with the lowest agreement was hair loss (κ=–0.05). With regard to the latency of symptom entry into the review, hardly any difference was demonstrated between symptoms that were entered from days 1 to 3 and from days 4 to 7 before the intended review (κ=0.40 vs κ=0.39, respectively). In contrast, for symptoms that were entered 15 to 21 days before the intended review, no congruency was demonstrated (κ=–0.15). Congruency levels seemed to be unrelated to the type of cancer, demographics, and physicians’ review experience. CONCLUSIONS The shared monitoring and review of symptoms between patients and clinicians has the potential to improve the understanding of patient self-reporting. Our data indicate that the integration of ePRO into oncological clinical research and continuous clinical practice provides reliable information for self-empowerment and the timely intervention of symptoms. CLINICALTRIAL ClinicalTrials.gov NCT03578731; https://clinicaltrials.gov/ct2/show/NCT03578731

Evaluation of immune-related adverse events (irAE): Utilizing the patient-reported outcomes of the common terminology criteria for adverse events (PRO-CTCAE) in a phase II study of ipilimumab (ipi) in men with castration-sensitive prostate cancer (CSPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24174-e24174
Author(s):  
Daniel Vargas Pivato de Almeida ◽  
Justine Anderson ◽  
Daniel Costin Danila ◽  
Michael J. Morris ◽  
Susan F. Slovin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Patient Reported Outcomes ◽  
Potential Role ◽  
De Novo ◽  
Limited Data ◽  
Patient Reported ◽  
The Common ◽  
Clinical Trial Information

e24174 Background: Incorporation of the PRO-CTCAE during chemotherapy is associated with fewer ER visits and improved survival. Limited data exist using this tool to capture irAE in immunotherapy trials. We collected select PRO-CTCAEs in a clinical trial evaluating an immune checkpoint inhibitor (ICI) in patients (pts) with CSPC. Methods: Cohort A (Coh A) enrolled de novo metastatic CSPC; Cohort B (Coh B) enrolled recurrent CSPC after radical prostatectomy (RP). Treatment consisted of 4 doses of ipi and 8 months of androgen deprivation therapy (ADT) in Coh A & B, and RP in Coh A. PRO-CTCAEs were collected at each ipi or ADT administration, and during follow-up. PRO-CTCAE items included abdominal pain, diarrhea, fatigue, anorexia, nausea, vomiting, rash and pruritus, with the correspondent attributes of frequency (freq), severity (sev), interference (int), and presence. Results: 16 pts were treated (Coh A: 7; Coh B: 9) with 181 matched pairs of PRO-CTCAE and CTCAE. The study was terminated early for an unfavorable risk:benefit ratio. PRO-CTCAE completion at required visits was 85.4% in Coh A and 98.1% in Coh B. Cohen’s kappa coefficients was lowest for pruritus (k = 0.10, slight agreement) and highest for rash (k = 0.64, moderate agreement). CTCAE captured diarrhea in 10 pts, 4 of whom received steroids. 75% (3/4) of pts receiving steroids graded diarrhea as ‘frequently’ or ‘almost constantly’ on the PRO-CTCAE while 66.7% (4/6) of those who did not receive steroids reported the same frequency. Conclusions: IrAE were more commonly reported and of higher grade by patients using the PRO-CTCAE as compared to clinician reporting, consistent with existing literature in non-ICI studies. Diarrhea as reported by the PRO-CTCAE did not associate with steroid use in this small trial. Further studies are needed to evaluate irAE using PRO-CTCAEs and the potential role in management of these toxicities. Clinical trial information: NCT02020070 . [Table: see text]

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