Operational Challenges of an Asia-Pacific Academic Oncology Clinical Trial

PURPOSEThe Asia-Pacific (APAC) region is a major focus for multinational clinical trials, although its cultural, linguistic, economic, and regulatory diversity pose significant challenges for trial conduct, particularly for academic clinical trials.METHODSWe describe our experience running the investigator-initiated phase III randomized, fully accrued, Aspirin for Dukes C and high-risk Dukes B Colorectal cancer trial (ASCOLT, ClinicalTrials.gov identifier: NCT00565708, N = 1,587), studying the benefit of aspirin in resected high-risk colorectal cancer. ASCOLT opened in 2008 and is the first large academic adjuvant trial fully conducted in the APAC region. Centrally coordinated by the Trial Management Team at the National Cancer Centre Singapore, it has involved 74 sites across 12 APAC countries/regions, including five middle-income countries.RESULTSChallenges encountered included regulatory complexity, communication and logistical barriers, limited funding and resources, disparate experience and infrastructure across sites, recruitment holds because of changes in local laws, patient attrition, and disruptions caused by the COVID-19 pandemic. Over 100 contracts and 49 ethics board reviews were required, contributing to a lengthy prestudy preparation time of 2 years and start-up times of approximately 6 months per site. Some of the mitigating actions included engaging local cooperative groups (eg, the Australasian Gastro-Intestinal Trials Group in Australia and New Zealand) and seven contract research organizations to manage sites, regular communication with the central team, transition to electronic data management, and a centralized drug-dispensing system.CONCLUSIONTo ensure an efficient and patient-centered clinical trials environment in the APAC region and sustained growth, we suggest coordinated approaches to harmonize regulatory processes, APAC academic oncology trials consortia to streamline processes and provide governance, and ongoing commitment from governments, funding agents, and industry

Progression-free survival analysis.

<p>Abbreviation: HR, hazard ratio; CI, confidence interval; NE, not estimable.</p>a<p>P values for age at diagnosis, CA125 and HER2 amplification ratio were based on Wald test, and P values for all other variables were based on the log-rank test.</p>b<p>Based on Wald test.</p>c<p>To interpret with caution as there were <10 deaths in the fitted multivariable model.</p

Clinicopathologic features by HER2 status.

<p>Abbreviation: OGD, oesophagogastroduodenoscopy.</p

HER2 amplification, age, and frequency of cancers reported in family history of mEOC.

<p>(A) Previous genome-wide copy number alteration study on a small cohort of mEOC (n = 17) showed significant amplification of HER2. x-axis shows chromosomes 1-X, with alternating gray blocks. y-axis is the −log(q) where q is the false discovery rate. Positive values indicate amplification and negative values are deletion. (B) Age distribution was of normal distribution overall and for both HER2+ and HER2− cases. The median age was 48.3 (range: 15 to 89 years). (C) Frequency of reported cancers in family history. Majority of cancers were of breast and gastrointestinal (colon/stomach) origin. Note: some patients reported more than 1 case of cancer in family history.</p

Survival outcomes by HER2 status.

<p>No statistical significance was observed for HER2+ compared to HER2− cases in (A) overall survival (log-rank p = 0.249), and (B) progression free survival (log-rank p = 0.120).</p