Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC

The utility of Aspirin in dukes C and high risk dukes B colorectal cancer - The ASCOLT study: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>High quality evidence indicates that aspirin is effective in reducing colorectal polyps; and numerous epidemiological studies point towards an ability to prevent colorectal cancer. However the role of Aspirin as an adjuvant agent in patients with established cancers remains to be defined. Recently a nested case-control study within the Nurses Health cohort suggested that the initiation of Aspirin <it>after </it>the diagnosis of colon cancer reduced overall colorectal cancer specific mortality. Although this data is supportive of Aspirin's biological activity in this disease and possible role in adjuvant therapy, it needs to be confirmed in a randomized prospective trial.</p> <p>Methods/Design</p> <p>We hypothesize through this randomized, placebo-controlled adjuvant study, that Aspirin in patients with dukes C or high risk dukes B colorectal cancer (ASCOLT) can improve survival in this patient population over placebo control. The primary endpoint of this study is Disease Free Survival and the secondary Endpoint is 5 yr Overall Survival. This study will randomize eligible patients with Dukes C or high risk Dukes B colorectal cancer, after completion of surgery and standard adjuvant chemotherapy (+/- radiation therapy for rectal cancer patients) to 200 mg Aspirin or Placebo for 3 years. Stratification factors include study centre, rectal or colon cancer stage, and type of adjuvant chemotherapy (exposed/not exposed to oxaliplatin). After randomization, patient will be followed up with 3 monthly assessments whilst on study drug and for a total of 5 years. Patients with active peptic ulcer disease, bleeding diathesis or on treatment with aspirin or anti-platelet agents will be excluded from the study.</p> <p>Discussion</p> <p>This study aims to evaluate Aspirin's role as an adjuvant treatment in colorectal cancer. If indeed found to be beneficial, because aspirin is cheap, accessible and easy to administer, it will positively impact the lives of many individuals in Asia and globally.</p> <p>Trials Registration</p> <p>Clinicaltrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00565708">NCT00565708</a></p

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

Phase II trial of gemcitabine in combination with cisplatin in inoperable or advanced hepatocellular carcinoma

Introduction: Advanced hepatocellular carcinoma (HCC) has a dismal prognosis and is notoriously chemo-resistant. We conducted a Phase II prospective study to evaluate the activity and tolerability of gemcitabine and cisplatin in chemo-naïve advanced hepatocellular carcinoma. The trial considered a “no further interest” response rate of 10% and a target response rate of 30%. Utilising a Simon’s minimax two-stage design with a type I error of 0.05 and power of 80%, 25 subjects would be required. Fifteen patients would be needed in stage 1 and if fewer than 2 responses were observed, the trial would be stopped and lack of efficacy claimed. Materials and Methods: Patients with advanced HCC, diagnosed based on histology or by World Health Organization (WHO) criteria, were administered gemcitabine 1000 mg/m2 and cisplatin 25 mg/ m2 on day 1 and day 8 of a 21-day schedule. Assessment of response based on computer tomography was performed after every 2 cycles of chemotherapy. Results: The trial was stopped early due to a lack of efficacy. A total of 15 patients were accrued. Twelve patients were hepatitis B positive and the other 3 patients were negative for both hepatitis B and C. Only 1 patient had a history of prior heavy alcohol use. Two patients had Child C liver cirrhosis, 5 patients had Child B cirrhosis, and the remaining 8 patients had Child A cirrhosis. This regime was well tolerated and there was only 1 patient who experienced grade IV toxicities. Only 5 of 15 patients experienced grade III toxicities (nausea and emesis, 1 patient; anemia, 1 patient; thrombocytopenia, 1 patient; and neutropaenia, 2 patients). Only 1 patient experienced a partial response to the combination of gemcitabine and cisplatin. A further 3 patients experienced stable disease and 11 patients progressed on chemotherapy. The median time to progression was 6 weeks. The progression-free curve showed a sharp descent in the initial part of the study, suggesting that many patients had disease progression after enrolment. The median overall survival was 18 weeks. Conclusion: The progression-free survival and overall survival in our study were extremely short. Based on the results of our phase 2 study, we are unable to recommend further studies utilising gemcitabine and cisplatin combination in patients with advanced HC

Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

Purpose: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)–pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. Experimental Design: DCs were cultured from peripheral blood mononuclear cells (PBMC), pulsed with the allogeneic MCL, and matured using cytokines that achieved high CD83- and CCR7-expressing DCs. Each patient received up to 10 intradermal vaccinations (3-5 × 106 cells per dose) at biweekly intervals. Results: Twenty patients received a total of 161 vaccinations. Treatment was well tolerated and quality of life measurements did not vary much across time. One patient experienced partial response [5%; 95% confidence interval (CI), 1-24%] and seven achieved stable disease (35%; 95% CI, 18-57%), one of whom also achieved late tumor regression, yielding a clinical benefit response rate of 40% (95% CI, 22-61%). Although overall median progression-free survival was 2.4 months (95% CI, 1.9-4.1 months), five patients (25%) experienced prolonged progression-free survival (>6 months), two of whom (10%) remain progression-free for >27 and >37 months, respectively. This result is particularly meaningful as all patients had progressive disease before treatment. Overall, DC vaccination was associated with a serial decline in regulatory T cells. Using an antibody array, we characterized plasma protein profiles in responding patients that may correlate with vaccine activity and report a prevaccination protein signature distinguishing responders from nonresponders. Conclusion: This phase II vaccine study using mature, MCL-pulsed DCs has shown promising results and warrants further evaluation in a prospective randomized setting