Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: A report from the New Agents Group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

Abstract Purpose: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain.Methods: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early-Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects.Results: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate).Conclusions: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.

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Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP)

Clinical & Translational Oncology ◽

10.1007/s12094-020-02399-3 ◽

2020 ◽

Cited By ~ 1

Author(s):

A. Rubio-San-Simón ◽

J. Verdú-Amorós ◽

R. Hladun ◽

A. Juan-Ribelles ◽

M. Molero ◽

...

Keyword(s):

Clinical Trials ◽

Childhood Cancer ◽

Early Phase ◽

New Agents ◽

Spanish Society ◽

Paediatric Haematology ◽

Early Phase Clinical Trials

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Molecular profiling of advanced solid tumours. The impact of experimental molecular-matched therapies on cancer patient outcomes in early-phase trials: the MAST study

British Journal of Cancer ◽

10.1038/s41416-021-01502-x ◽

2021 ◽

Author(s):

Valentina Gambardella ◽

Pasquale Lombardi ◽

Juan Antonio Carbonell-Asins ◽

Noelia Tarazona ◽

Juan Miguel Cejalvo ◽

...

Keyword(s):

Early Phase ◽

Progression Free Survival ◽

Tumor Board ◽

Prior Therapy ◽

Early Phase Trials ◽

Molecular Tumor Board ◽

Early Phase Clinical Trials ◽

The Impact ◽

To Receive

Abstract Introduction Molecular-matched therapies have revolutionized cancer treatment. We evaluated the improvement in clinical outcomes of applying an in-house customized Next Generation Sequencing panel in a single institution. Methods Patients with advanced solid tumors were molecularly selected to receive a molecular-matched treatment into early phase clinical trials versus best investigators choice, according to the evaluation of a multidisciplinary molecular tumor board. The primary endpoint was progression-free survival (PFS) assessed by the ratio of patients presenting 1.3-fold longer PFS on matched therapy (PFS2) than with prior therapy (PFS1). Results Of a total of 231 molecularly screened patients, 87 were eligible for analysis. Patients who received matched therapy had a higher median PFS2 (6.47 months; 95% CI, 2.24–14.43) compared to those who received standard therapy (2.76 months; 95% CI, 2.14–3.91, Log-rank p = 0.022). The proportion of patients with a PFS2/PFS1 ratio over 1.3 was significantly higher in the experimental arm (0.33 vs 0.08; p = 0.008). Discussion We demonstrate the pivotal role of the institutional molecular tumor board in evaluating the results of a customized NGS panel. This process optimizes the selection of available therapies, improving disease control. Prospective randomized trials are needed to confirm this approach and open the door to expanded drug access.

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Influence of early-phase clinical trial enrollment on patterns of end-of-life care for children with advanced cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.26_suppl.151 ◽

2016 ◽

Vol 34 (26_suppl) ◽

pp. 151-151 ◽

Cited By ~ 1

Author(s):

Prasanna Janaki Ananth ◽

Chalinee Monsereenusorn ◽

Clement Ma ◽

Hasan Al-Sayegh ◽

Joanne Wolfe ◽

...

Keyword(s):

Advanced Cancer ◽

Early Phase ◽

Hospital Admissions ◽

Medical Procedures ◽

Early Phase Clinical Trial ◽

Phase Clinical Trial ◽

Clinical Trial Enrollment ◽

Early Phase Clinical Trials ◽

Eol Care ◽

Clinic Visits

151 Background: Early phase clinical trials are critical to enhancing therapies for children with advanced cancer. However, trial enrollment may intensify end-of-life (EOL) care. We evaluated patterns of EOL care for patients at a large cancer center. Methods: Single-center, retrospective cohort study of pediatric oncology patients, ages 6 months-21 years, who died in 2010-2014. We queried electronic medical records to assess frequencies of medical procedures (e.g. intubations), clinic visits, and hospital admissions in the last 6 months of life. We assessed timing of pediatric palliative care (PPC) consultation, initial advance care planning (ACP) discussion, and entry of do-not-attempt resuscitation (DNAR) orders in the chart, in relation to date of death. Patients enrolled in early phase clinical trials for at least 1 cycle (EP) were compared with those not enrolled (NEP), using Wilcoxon rank sum and Fisher exact tests. Results: For N = 125 patients, median age at death was 11.6 years (IQR 5.8-16.3); 46% were female; 70% were White, non-Hispanic. 26% were trial enrollees. Diagnoses included 42% solid tumors, 41% brain tumors, and 18% hematologic malignancies. Most patients had PPC consultation (83%), ACP discussions (91%), and DNAR orders (86%). EP and NEP cohorts did not significantly differ in baseline demographic or clinical characteristics, frequencies of medical procedures, or hospital admissions. EP patients had a higher median number of clinic visits than NEP patients (18.5 [16.3-27.2] vs. 14.1 [6.5-20.7], p = 0.0003) and received PPC consultation significantly closer to death than NEP patients (median days before death = 58 [16-84] vs. 85 [32-173], p = 0.04). There was no difference between EP and NEP patients in timing of initial ACP discussion or of DNAR order entry. Conclusions: Near the EOL, EP patients had more frequent clinic visits and later PPC consultation, but trial enrollment did not appear to delay ACP discussions or increase hospital resource use. These results suggest that early phase clinical trial enrollment does not substantially alter EOL care patterns for children with advanced cancer.

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Psilocybin: From Serendipity to Credibility?

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.659044 ◽

2021 ◽

Vol 12 ◽

Author(s):

James J. Rucker ◽

Allan H. Young

Keyword(s):

Early Phase ◽

Clinical Trial Data ◽

Nuremberg Code ◽

Treatment Development ◽

Early Phase Clinical Trial ◽

Early Phase Trials ◽

History Of ◽

Phase Clinical Trial ◽

Early Phase Clinical Trials ◽

Do So

Psilocybin has a long history of non-medical use and some seem to infer from this that it has therapeutic utility. Early phase clinical trials with psilocybin are encouraging, but suggest only that larger, multicentre trials are required. These are ongoing but will take many years to complete. Meanwhile, retreat centers offering paid experiences with psilocybin truffles have opened in some countries, often using early phase clinical trial data as a basis for bold, public facing claims. This seems unwise. Early phase trials are not designed for their results to be generalized outside the setting they were undertaken in. To do so risks being misleading. Providing what may be seen as an unregulated drug intervention as a paid service is difficult to reconcile with long-held ethical principles underpinning human research and treatment development that were laid down by the 1947 Nuremberg Code and the 1962 Kefauver Harris Amendments. By using psilocybin before it has been properly tested, retreat centers may be undermining their own credibility and the credibility of the wider field.

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Economic growth of BRIC nations and access to early-phase oncology clinical trials: An overview.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e17554 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e17554-e17554

Author(s):

Heloisa Veasey Rodrigues ◽

Prasanth Ganesan ◽

Xiaochun Liu ◽

Vivek Subbiah

Keyword(s):

Economic Growth ◽

Clinical Trials ◽

Early Phase ◽

Kinase Inhibitors ◽

Current Status ◽

The Road ◽

Bric Countries ◽

Oncology Clinical Trials ◽

Early Phase Clinical Trials ◽

The Impact

e17554 Background: With increasing globalization we have witnessed exponential economic growth in the BRIC (Brazil, Russia, India and China) nations. Concurrently, clinical trials have been outsourced to these countries. We sought to investigate the current status of early phase oncology clinical trials in the BRIC countries, exemplifying the impact of these emerging economies and global markets in health care. Methods: We reviewed the clinicaltrials.gov database for registered early phase trials (Phase I/II) in the BRIC countries; 2. We looked at research from these countries collectively. 3. We reviewed specific challenges and prognosticated the road ahead through a literature review. Results: We identified374 active early phase clinical trials in BRIC countries as of October 2012. China had 68% (255/374) of the trials, Brazil 14% (51/374), Russia 12% (47/374) and India 6% (21/374). Twenty-three trials were registered in more than one BRIC; therefore we analyzed 348 different trials. Gastrointestinal (20%, 70/348), lung (19%, 67/348) and breast (17%, 57/348) cancers were the most studied. Most of the trials were sponsored by universities or hospitals (51%, 176/348) and most conducted in a single country (73%, 247/348) with 70% of therapy intended to be palliative (243/348). Combined agents were most commonly studied (57%, 199/348). Among the 217 targeted-agent trials, 23% targeted the EGFR pathway, 18% the VEGFR, 11% involved multi-tyrosine kinase inhibitors and 10% the PI3K-mTOR pathway. Funding mechanisms and sponsorship of studies were disparate. Industry-sponsored studies comprised 24% (62/255) in China, 96% (45/47) in Russia, 80% (41/51) in Brazil and 57% (12/21) in India. Conclusions: Despite theeconomic explosion and shift of non-oncology clinical trials to BRIC nations, USA and Europe still lead in conducting early phase clinical trials in oncology. China accounts for 19% of world’s population and has the majority (68%) of trials while India (17% of World’s population) has only 6%. A dominance of industry-sponsored studies in BRIC countries other than China was found. Significant challenges in infrastructure and trained personnel remain, but efforts to overcome them are underway.

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