Comorbidities limiting recruitment of colorectal cancer (CRC) patients in early-phase trials.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 791-791
Author(s):  
Narjust Duma ◽  
Yucai Wang ◽  
Miguel Gonzalez Velez ◽  
Sejal Kothadia ◽  
Veronica Mariotti ◽  
...  
Keyword(s):  
Phase I ◽  
Early Phase ◽  
Nyha Class ◽  
Anticoagulation Therapy ◽  
The United States ◽  
Exclusion Criterion ◽  
Eligibility Criteria ◽  
Trial Protocols ◽  
Early Phase Clinical Trials ◽  
Therapy Location

791 Background: With the surge of drug development in the past decade, early phase clinical trials (EPCT) have gained value evaluating the potential benefits of new therapies. The inclusion/exclusion criteria in EPCT are usually rigorous and may exclude many patients (pts) commonly seen in clinical practice. Our objective was to identify the most common comorbidities excluded in EPCT for CRC. Methods: ClinicalTrials.gov was queried on December 1stof 2015. We reviewed the characteristics and eligibility criteria of 369 phase I/II interventional drug trials including: experimental arm therapy, location, and exclusion/inclusion criteria. Logistic regressions were completed and exclusion was studied as a binary variable. Results: Of the 369 trials, 68% were phase II and 32% phase I. 46% were conducted in the United States, 30% in Europe, 15% in Asia and 9% in other locations. 74 (20%) trials excluded pts > 70 years of age. 142 (39%) trials required creatinine levels < 1.5 mg/dl, liver enzymes (AST/ALT) < 2.5 and bilirubin < 1.5 of the upper limit of normal. Cytopenia was a significant exclusion factor: 147 (47%) trials required Hgb > 9 g/dl and 218 (59%) excluded pts with platelets < 100,000/dl. In terms of comorbidities, 98 (27%) trials excluded pts with heart failure (NYHA class 3/4), 74 (20%) with atrial fibrillation, 112 (31%) with any anticoagulation therapy and 155 (42%) with positive HIV. Trials located in the US were more likely to exclude pts with Hgb < 9g/dl (OR: 1.5, 95%CI: 1.1-2.3, p < 0.05), immunotherapy trials were more likely to exclude pts on any anticoagulation (OR:1.8, 95%CI: 1.2-2.8, p < 0.007) and targeted therapy trials were more likely to exclude pts with history of DVT/PE or cardiovascular diseases (OR: 3.4, 95%CI: 1.9-5.8, p < 0.0001; OR: 2.3, 95%CI: 1.3-3.8, p < 0.002, respectively). Conclusions: 20% of EPCTs on CRC excluded pts with advanced age, organ dysfunction and common comorbidities. Many of the EPCT reviewed were not inclusive of our aging oncology population who are more likely to have multiple comorbidities. Investigators should review whether sufficient justification exists for every exclusion criterion before their incorporation in future trial protocols.

scholarly journals Phase I prognostic online (PIPO): A web tool to improve patient selection for oncology early phase clinical trials

2021 ◽  
Vol 155 ◽  
pp. 168-178
Author(s):  
Ignacio Matos ◽  
Guillermo Villacampa ◽  
Cinta Hierro ◽  
Juan Martin-Liberal ◽  
Roger Berché ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Patient Selection ◽  
Early Phase ◽  
Web Tool ◽  
Improve Patient Selection ◽  
Selection For ◽  
Early Phase Clinical Trials ◽  
Improve Patient

Re-evaluating eligibility criteria: Analysis of factors leading to nonparticipation and outcomes of patients (pt) with advanced cancer who signed consent but were not treated in early-phase immunotherapy (IO) trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2552-2552
Author(s):  
Roberto Carmagnani Pestana ◽  
Ishwaria Mohan Subbiah ◽  
Kenneth R. Hess ◽  
Le Huang ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Phase I ◽  
Advanced Cancer ◽  
Early Phase ◽  
Detailed Examination ◽  
Median Number ◽  
Phase I Trials ◽  
Eligibility Criteria ◽  
Alternate Therapy ◽  
Modifiable Factors ◽  
Metastatic Sites

2552 Background: Eligibility criteria protect the safety of trial pt and delineate the study population. Excessively restrictive criteria, however, can negatively impact accrual and prevent access to beneficial investigational treatments. Recently, ASCO issued a statement on the need to broaden eligibility criteria and make trials more representative. We aim to characterize the factors leading to non-participation and the outcomes of pt who signed consent for phase I IO trials but ultimately did not receive any therapy on that trial. Methods: We identified 696 consecutive pt w/ advanced cancer who consented to participate on IO phase I trials from 10/2015-12/2017, and collected pt characteristics as well as clinical outcomes, and compared participants (P) to non-participants (NP). Results: Among the 696 pt who initially consented to participate on IO phase I trials, 178 (25.6%) were never treated. Median age was 60 in both groups, and there were no differences regarding median number of metastatic sites (n = 2 vs 2 ) or sex distribution (F 53% vs 54%); NP had received less lines of therapy (median = 3 vs 4, p = 0.016). Reasons for non-participation were: 48 (26%) alternate therapy (for 18, geography was the main reason), 29 (16%) clinical progression/ decline in PS, 14 (8%) did not have enough biopsy tissue, 13 (7%) new lab abnormality, 11 (6%) new brain mets, 63 (35%) had other reasons (death, concurrent medications, financial factors). Median time from signature of consent to final exclusion of trial was 19 days (0-82). 54 of NP eventually enrolled in other trial, including 29 in immunotherapy trial. Median overall survival (OS) was significantly lower for NP vs P (median 6.9 vs 18.0, HR 0.5; p < .0001). Conclusions: One quarter of patients who signed consent for early-phase immunotherapy trials were unable to start on study. NP had significantly decreased OS. Detailed examination of these reasons can lead to recognition of modifiable factors and streamline the pretrial period, to guarantee this vulnerable population has maximal access to start therapy on study.

scholarly journals Patient (pt) selection for immunotherapeutic early-phase clinical trials (ieCTs): A single phase I unit experience

2019 ◽  
Vol 30 ◽  
pp. v186
Author(s):  
M. Simonelli ◽  
E. Lorenzi ◽  
A. Dipasquale ◽  
P. Persico ◽  
G. Ninatti ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Early Phase ◽  
Single Phase ◽  
Selection For ◽  
Early Phase Clinical Trials

scholarly journals Access to early phase clinical trials for children with relapsed and refractory neuroblastoma. A multicentre international study.

2021 ◽  
Author(s):  
Marta Cortes ◽  
Fernando Carceller ◽  
Alba Rubio-San-Simon ◽  
Sucheta Vaidya ◽  
Francisco Bautista ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Performance Status ◽  
International Study ◽  
Eligibility Criteria ◽  
Early Phase Trials ◽  
Novel Drugs ◽  
Innovative Therapies ◽  
Early Phase Clinical Trials ◽  
Relapsed Disease

Objectives. Neuroblastoma is the most common extracranial tumour in children, and prognosis for refractory and relapsed disease is still poor. Early Phase clinical trials play a pivotal role in the development of novel drugs. Ensuring adequate recruitment is crucial. The primary aim was to determine the rate of participation trials for children with refractory/relapsed neuroblastoma in two of the largest Drug Development European institutions. Methods. Data from patients diagnosed with refractory/relapsed neuroblastoma between January 2012 and December 2018 at the two institutions were collected and analysed. Results. Overall, 48 patients were included. A total of 31 (65%) refractory/relapsed cases were enrolled in early Phase trials. The main reasons for not participating in clinical trials included: not fulfilling eligibility criteria prior to consent (12/17, 70%) and screening failure (2/17, 12%). Median time on trial was 4.3 months (range 0.6-13.4). Most common cause for trial discontinuation was disease progression (67.7%). Median overall survival was longer in refractory (28 months, 95% CI, 20.9-40.2) than in relapsed patients (14 months, 95% CI, 8.1-20.1)) [p=0,034]. Conclusions. Although two thirds of children with refractory/relapsed neuroblastoma were enrolled in early Phase trials, recruitment rates can still be improved. The main cause for not participating on trials was not fulfilling eligibility criteria prior to consent, mainly due to performance status and short life expectancy. This study highlights the hurdles to access to innovative therapies for children with relapsed/refractory neuroblastomas and identifies key areas of development to improve recruitment to early phase trials.

Distinct radiological patterns of drug-induced pneumonitis (R-DIP) in early-phase clinical trials and predictive factors affecting outcome: A 10-year systematic review from the Royal Marsden Hospital Phase I Drug Development Unit experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3088-3088
Author(s):  
Angelika Terbuch ◽  
Irene Moreno Candilejo ◽  
Mariana Scaranti ◽  
Daniel Bar ◽  
Miriam Estevez Timon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Predictive Factors ◽  
Early Phase ◽  
Clinical Symptoms ◽  
Phase I Clinical Trials ◽  
Factors Affecting ◽  
Experienced Radiologist ◽  
Radiological Patterns ◽  
Early Phase Clinical Trials

3088 Background: We studied clinical and radiological parameters influencing DIP in patients (pts) participating in phase I clinical trials, aiming to investigate predictive factors affecting DIP, in particular those affecting outcome. Methods: 2439 consecutive stage IV cancer pts on phase I clinical trials from 2007 to 2017 were identified. Pts with respiratory symptoms or abnormal lung imaging were reviewed in detail, with longitudinal analysis of imaging by an experienced radiologist. R-DIP was categorized according to internationally recognized criteria. Results: 60 pts developed R-DIP (overall incidence 2.5%); most frequent in pts receiving drug conjugates (31.1%) followed by targeted therapies (8.3%). Hypersensitivity pneumonitis was most common (33.3%) followed by non-specific interstitial pneumonitis (30%) and cryptogenic organising pneumonitis (26.7%). 45% pts who developed R-DIP were clinically asymptomatic. The number of affected lobes (OR 1.47, 95% CI: 1.19-1.81, p < 0.001) and the pattern of R-DIP (OR 5.83 for ARDS, 95% CI: 0.38-90.26, p = 0.002) were significantly associated with a higher CTCAE pneumonitis grading. 23% pts (14/60) had investigational medicinal product (IMP) temporarily discontinued or had a dose reduction while 42% pts (25/60) had IMP permanently discontinued. 48% pts were treated with steroids. The number of affected lobes, pattern of R-DIP and steroid therapy did not influence an improvement in R-DIP (p = 0.65, 0.27 and 0.23 respectively). Continuation of treatment resulted in worsening of DIP in 42.9% of cases. The only predictive factor for an improvement in DIP was an interruption of treatment (OR 0.05, 95% CI: 0.01-0.35, p = 0.01). 14 pts were retreated with a reoccurrence of R-DIP in 4 pts (28.6%). Conclusions: R-DIP from novel agents in early phase clinical trials presents in varied radiological patterns, with findings often preceding clinical symptoms. Treatment interruption leads to improvement of DIP and should be considered early. Close clinical and radiological surveillance is recommended should IMP be restarted.

scholarly journals P05.08 High-grade gliomas and immunotherapeutic early phase clinical trials: a single-center experience

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii35-iii36
Author(s):  
M Simonelli ◽  
P Persico ◽  
A Dipasquale ◽  
E Lorenzi ◽  
L Giordano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Early Phase ◽  
Univariate Analysis ◽  
Methylation Status ◽  
High Grade ◽  
Clinical Factors ◽  
Lymphocyte Ratio ◽  
High Grade Gliomas ◽  
Early Phase Clinical Trials

Abstract BACKGROUND Patients with high-grade gliomas (HGGs) have historically been excluded from immunotherapeutic early-phase clinical trials (ieCTs) due to unavailability of serial bioptic sampling, the frequent need of corticosteroids, concerns regarding activity of immunotherapy in central nervous system, and rapid clinical deterioration. MATERIAL AND METHODS We retrospectively reviewed data of all recurrent HGG patients enrolled in ieCTs at Humanitas Cancer Center Phase I Unit between 2014 and 2019. Disease control rate (DCR) according to RANO criteria, six-months progression-free and overall survival (PFS-6; OS-6), and treatment-related adverse events (TRAEs), were evaluated. A control-cohort (CC) of patients treated with standard treatments (temozolomide, fotemustine, lomustine and procarbazine, bevacizumab) matched (1:1) for sex, age, line of treatment, MGMT methylation status, and IDH mutational status, was selected for comparison. A series of clinical parameters with an established prognostic value for patients with solid tumors treated into ieCTs were correlated with survivals through an univariate analysis. These include: use of steroids, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, lactate dehydrogenase, albumin, total protein. RESULTS Five among the 23 ieCTs conducted at our Phase I Unit allowed inclusion of HGG patients. 25 patients were enrolled in the experimental cohort (EC): 22 (88%) glioblastoma, 3 (12%) anaplastic astrocytoma. Median age was 50 years (range 25–71); 16 patients (64%) were men, 9 (36%) women; 17 pts (68%) required steroid therapy, with a median baseline dexamethasone dose of 2 mg (range 1–6). The median number of prior systemic therapies was 1 (range 1–2). Twelve patients (48%) received monotherapies (anti PD-1, anti CSFR-1, anti TGF-ß, anti cereblon), 13 (52%) combination regimens (anti PD-L1 + anti CD38, anti PD-1 + anti CSFR-1). DCR was 40% (1 CR + 2 PR + 7 SD) and 37% (9 SD), in EC and CC, respectively. Four patients (16%) in EC had grade ≥3 TRAEs (1 neutropenia, 1 pneumonia, 2 hepatitis). With a median follow-up of 14 months PFS-6 were 35% and 16% (p=0.075), in EC and CC respectively, while OS-6 was significantly improved in the EC (82% vs 44%, p=0.004). In our small series, none of clinical factors resulted prognostic. CONCLUSION Survival outcomes of ourHGG patients treated into ieCTs compared very favorably with a matched CC. Inclusion of HGGs patients into ieCTs should be strongly encouraged. Identification of clinical factors to select who may benefit from ieCTs still remains crucial.

scholarly journals Therapeutic outcome of early-phase clinical trials in multiple myeloma: a meta-analysis

2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Niels van Nieuwenhuijzen ◽  
Rowan Frunt ◽  
Anne M. May ◽  
Monique C. Minnema
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Early Phase ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Phase I Trials ◽  
Phase Ii Trials ◽  
Early Phase Clinical Trials

AbstractGreat progress in the treatment of patients with multiple myeloma (MM) has been made due to the development of novel drugs. Patients with relapsed/refractory MM (RRMM) can be enrolled in early-phase clinical trials, but their performance across the last decade is unknown. We conducted a meta-analysis on the overall response rate (ORR) and toxicity. PubMed, Embase, and Cochrane Library were systematically searched for phase I and phase II trials investigating an experimental compound as a single agent or in combination with dexamethasone, published from January 1, 2010 to July 1, 2020. Eighty-eight articles were included, describing 61 phase I trials involving 1835 patients and 37 phase II trials involving 2644 patients. There was a high degree of heterogeneity. Using a random-effects model, the 95% CIs of the estimated ORR were 8–17% for phase I trials and 18–28% for phase II trials. There were significant subgroup differences in ORR between the years of publication in phase I trials and between drug classes in both phase I and phase II trials. The ORR in early-phase clinical trials in RRMM is substantial, especially in phase II trials, but due to high heterogeneity a general assessment of clinical benefit before participation is difficult to offer to patients.

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