Clinical trials

Hepatocellular carcinoma (HCC) is the 7th most common cancer worldwide but is the 4th deadliest, because diagnosis tend to be late and current systemic therapies are poorly efficacious. Within the same tumour, different parts of the HCC can belong to separate molecular sub-groups. In addition, there is currently no validated predictive biomarkers to help clinicians select the best therapy for an individual patient. This challenge poses an urgent, unmet clinical need. To address this, the multi-disciplinary research program Precision Medicine in Liver Cancer across an Asia-Pacific Network (PLANet 1.0) was conceptualized and successfully conducted from 2016-22. The program uncovered novel insights into the highly heterogeneous molecular landscape of HCC and novel mechanisms, including how HCC reverts to fetal forms to escape the body's immunological defence. These investigations will be continued in PLANet 2.0 and in this new phase, the research team will investigate patients receiving best-in-class therapeutics in 2 investigator-initiated clinical studies (AHCC12 and AHCC13), including Atezolizumab plus Bevacizumab (Atezo+Bev) and Yttrium-90, which allows the research team to collect longitudinal, before and after treatment biosamples and clinical data. These clinical studies will serve as proof-of-concept to the study team's translational findings and allow it to uncover predictive biomarkers which will help clinicians to institute more efficacious and personalized treatment in the future. The research team comprises of experts in different complementary fields (epigenomics, genomics, immunomics, metabolomics, proteomics, clinical science and data science) and across different institutions. This allows the team to adopt an integrative approach in understanding the landscape of the HCC tumour micro-environment and biomarkers co-localisation, and their role in tumour evolution and therapeutic response. By adopting a wide spectrum of converging investigations, PLANet 2.0 will identify and validate biomarkers that correlate with clinical outcomes (response, resistance and recurrence).

This is a single-centre, non-randomized, open label phase II trial to be conducted at the National Cancer Centre, Singapore (NCCS). Patients diagnosed with metastatic PDAC will be eligible to enrol. The investigators hypothesize the anticancer activity of low dose OXIRI (LD-OXIRI) regimen comprising of metronomic oxaliplatin (O) and metronomic capecitabine (xeloda; X) in combination with UGT1A1-directed dosing of irinotecan (IRI) to be a tolerable regimen in patients with advanced PDAC and will lead to a favourable response rate. Patients will be prospectively enrolled in two stages - In stage 1, patients will be recruited and evaluated for response and toxicity. In stage 2, more patients will be recruited for further evaluation of response and toxicity.

The purpose of this research study is to investigate the acceptability, feasibility, and effectiveness of exercise therapy and cognitive behavioral therapy (CBT) in improving fatigue levels and breast cancer treatment adherence in breast cancer patients.

This is a prospective, single-arm, non-randomized interventional study nested within the existing ELEGANCE cohort. Patients eligible for the RE-BALANCE study will be selected from the ELEGANCE cohort based on predefined high-risk criteria, specifically a low 12-non-hydroxy/12-hydroxy bile acid ratio indicative of elevated hepatocarcinogenic risk. The study comprises Baseline Assessments (Visit 1), Intervention Visits (Visit 2-8), and Follow-up Assessments (Visit 9-11).

ASTER is a multi-part study that aims to prospectively establish evidence for the implementation of aromatherapy as complementary therapy within cancer care in the Singapore context. ASTER 2 study evaluates how extracts from Asian aromatic plants with familiar aromas introduced as inhalation therapy can alleviate distress in breast cancer patients scheduled to undergo radiotherapy (RT).

This is a single arm screening study. All eligible participants will be subjected to low dose CT (LDCT) screening and biomarker testing. The primary aim of the study is to determine the feasibility of conducting LDCT screening in at-risk populations for lung cancer in Singapore: * For the smoker population, LDCT screening for lung cancer will be implemented in accordance to Academy of Medicine, Singapore screening test guidelines with the aim of investigating the feasibility of instituting lung cancer screening clinical service in Singapore. * For the non-smoker population, LDCT screening for lung cancer will be introduced to systematically collect baseline data to better understand and provide evidence for lung adenocarcinoma in never-smoker phenotype that is unique to East Asia/Singapore. This will help address unmet needs in local population research as reported by Academy of Medicine, Singapore, to validate risk factors and inform future screening guidelines for the at-risk population. Screening results will be reported based on Lung CT Screening Reporting \& Data System (Lung-RADS).

This observational study aims to assess the outcomes in patients with advanced treatment refractory cancers with matched molecular/precision therapy as per their molecular profiling results after discussion at molecular tumour board. 1. To standardize response assessment and data collection for patients that are receiving off-label or non-standard therapies based on MTB recommendations. \- Establish a standardized response assessment process and data collection patients that are receiving off-label or non-standard therapies based on MTB recommendations. 2. To demonstrate that it is feasible to standardize investigations and endpoints in this proof-of-concept study. * Through standard safety laboratory investigations (FBC, U/E/Cr, LFT) * Through standard radiological imaging at 6-12 weeks with the key endpoint being best response during that imaging window, and disease control rate at 6 months. Hypothesis: Our proposed IMPACT-INSPIRE study hypothesis is that standardised response assessment and data collection in patients with no available therapies receiving off-label systemic therapies, can provide a novel mechanism to assess oncological outcomes in this unique cohort of patients, generate hypothesis, and provide insights to future biomarker-driven drug development

This study aims to screen tumor molecular profile for better selection of anticancer treatment, in particular, allocation to clinical trials if available.

The goal of this clinical trial is to evaluate the clinical effectiveness and understand the biological mechanisms of electroacupuncture (EA) in reducing cognitive toxicity among cancer survivors. The study aims are: * To evaluate the clinical effectiveness of a 10-week EA regimen targeting neuropsychiatric-related acupoints in reducing cognitive toxicity among cancer survivors in Singapore. * To explore the biological mechanisms underlying EA's effects on cognitive function. * To assess the early implementation of EA for managing cognitive toxicity in cancer survivors. Researchers will compare results from the true EA arm, sham EA arm and waitlist control arm, to see if electroacupuncture can help improve cognitive issues related to cancer and its treatment, how it may work, and what factors may affect how it is delivered in cancer care. Participants will: * Be assigned to either of the 3 arms (true EA, sham EA, waitlist control) * Received 10 EA sessions (if assigned to true or sham EA arm) * Complete 3 study assessment visits at baseline, Week 13, and Week 17 * Be invited to a one-time interview to share their study experience (optional, if selected)

The current interdisciplinary specialist palliative care model focuses on supporting patients with advanced cancer who have complex problems in the last weeks of life. Consequently, palliative care is often provided late and in response to uncontrolled symptoms during crises. Palliative care models should shift from this reactionary illness-stress paradigm to a proactive health-wellness approach that is integrated early in the patient's disease trajectory. A proactive early palliative care telehealth model, ENABLE (Educate, Nurture, Advise, Before Life Ends), was developed in the U.S. to coach patients with advanced cancers and their family caregivers on how to cope effectively with serious illness. By empowering individuals early before acute distress and symptoms occur, patients and families can better mitigate and avoid crises. Building on positive health outcomes demonstrated by the ENABLE model in the U.S., the study team has successfully pilot-tested a culturally adapted ENABLE-SG model in Singapore. This study seeks to test the effectiveness of this ENABLE-SG model among patients with recently diagnosed advanced cancer and their caregivers while simultaneously collecting data on real-world implementation.

This study aims to compare clinical outcomes (informed choice and genetic counselling outcomes) and cost (provider and patient time, travel, and telehealth platform) between telegenetics and in-person genetic counselling.

Patients with "high-risk" locoregionally-advanced nasopharyngeal carcinoma (LA-NPC), defined as AJCC/UICC 8th edition TNM-stage III-IVA and high Epstein-Barr virus (EBV) DNA viral load (≥4,000 copies/mL) will require induction chemotherapy (IC) prior to chemo-radiation (CCRT) as per standard treatment. Patients who persist to manifest DETECTABLE EBV DNA following 3 cycles of IC have a higher risk of relapse, and are typically recommended for a year of low-dose oral chemotherapy after CCRT. RIBBON-LA-01 is a single-arm, open-label, phase 2 clinical trial of maintenance tislelizumab and metronomic capecitabine (metroCap) for 52 weeks after IC and CCRT, targeting this specific group of patients who have persistent detectable EBV DNA after IC. The main objective is to evaluate the efficacy of maintenance tislelizumab and metroCap in patients with DETECTABLE EBV DNA levels after 3 cycles of IC.

This is an open-label, investigator-initiated phase II clinical trial designed to evaluate the efficacy and safety of Sacituzumab Tirumotecan (sac-TMT) monotherapy in patients with recurrent or metastatic adenoid cystic carcinoma (ACC) of salivary gland origin and papillary thyroid carcinoma (PTC). A total of 68 patients will be enrolled over in 18-month period, with 34 patients in Cohort A (ACC) and 34 in Cohort B (PTC). All participants will receive sac-TMT at a dose of 4 mg/kg administered intravenously on Days 1 and 15 of each 28-day cycle. The primary endpoint is the objective response rate (ORR), defined as the proportion of patients achieving a complete or partial response as assessed by the site investigators. Secondary endpoints include progression-free survival, overall survival, disease control rate, safety and tolerability, dose intensity, and relative dose intensity.

This is a phase II study testing the combination of Pembrolizumab with Lenvatinib, a multi-kinase inhibitor that has activity against vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR1-4), ret protooncogene (RET), platelet-derived growth factor receptor-alpha (PDGFR-alpha) and KIT (a stem cell factor receptor), and letrozole, a non-steroidal aromatase inhibitor, in advanced hormone receptor (HR) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) that has progressed on/after standard endocrine therapy.

The HALT study aims to evaluate histotripsy in an Asian population for both primary (HCC, CCA) and secondary liver malignancies with liver-limited or oligoprogressive disease. In addition to safety and local control, the study incorporates translational endpoints including immune profiling (PBMCs, cytokines), microbiome shifts, and optional tumour biopsies. This trial will provide critical data on the feasibility, tolerability, and biological impact of histotripsy in a region with the highest burden of liver cancer.

To determine if diffusion aromatherapy exposure to an essential oil blend can potentially improve mild cognitive impairment/mild dementia symptoms and relieve caregiver stress. This study also allows us to gauge the willingness of elderly patients in complying with long-term aromatherapy treatments.

This is a multi-national, phase II, parallel-arm, double-blind, placebo-controlled, two-arm study designed to assess the efficacy and safety of SIRT-Y90 followed by atezolizumab plus bevacizumab \[study arm\], versus SIRT-Y90 followed by placebo \[control arm\] in patients with locally advanced Hepatocellular Carcinoma (HCC).

This is a single arm phase II study of adjuvant intra-dermal NA DC vaccine combined with intravenous nivolumab in patients with resectable HCC (group A) or CRLM (group B) planned for curative surgery (with/without local ablation).

The overall aim of the study is to evaluate the feasibility, acceptability and preliminary effects of the next iteration of iCareBreast+, an innovative breast care e-support intervention programme, by refining existing contents and building new contents based on comprehensive assessment of breast cancer women's needs and preferences among breast cancer patients undergoing chemotherapy. The specific objectives of this study are: 1. To develop a new iteration of an innovative smartphone-based self-care solution for patients with breast cancer undergoing chemotherapy (iCareBreast+); 2. To assess the feasibility and acceptability of iCareBreast+; and 3. To explore the preliminary effects of iCareBreast+ on the primary outcome of self-efficacy, and knowledge of breast cancer treatment, as well as secondary outcomes including anxiety, depression, health-related quality of life (HRQoL), social support and satisfaction with oncologic care.

The goal of this clinical trial is to evaluate the efficacy and safety of Pembrolizumab in combination with Olaparib in participants with relapsed/refractory Peripheral T-cell Lymphoma (PTCL). The study mainly aims to evaluate: * objective response rate (ORR) as per Cheson response criteria assessed by the independent central review * overall survival and progression-free survival * adverse events by CTCAE version 5.0 The administration of Pembrolizumab and Olaparib to participants will occur on Day 1 of each 3-week dosing cycle and will continue until disease progression or unacceptable toxicity, up to 35 cycles. Treatment with Olaparib will proceed continuously from Day 1 of Cycle 1, in 3-week dosing cycles in parallel with Pembrolizumab, up to 35 cycles, unless specific withdrawal/discontinuation criteria are met. After the end of treatment, each subject will be followed for 30 days for adverse event (AE) monitoring (serious AEs \[SAEs\] will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier).

This is a 24-week exercise programme consisting of aerobic exercise and muscle strength training, 3 sessions per week. The first 9 sessions are supervised by physiotherapists in person, followed by 63 sessions monitored remotely (video) or supervised by trainers at ActiveSG (Sport Singapore) gyms.

This is a multi-cohort proof of concept study involving patients with sarcomas or melanomas. Patient models, both two- and three-dimensional, will be derived from tumour samples. These will then be used to evaluate drug sensitivities ex vivo. Enrolled patients will undergo resections or biopsies as part of standard-of-care, which will be used to generate patient models. Patients will receive standard-of-care systemic treatment. Patient models will also be subjected up to a 14-drug screening panel. The majority of drugs in the respective drug panels has been shown to have activity in the respective cancers and would be used in the standard-of-care setting by treating physicians.

There are limited in depth studies on the epidemiology and clinical management of EGFR exon 20 insertion mutated NSCLC in Asia. In addition, there is preliminary data suggesting the exact location of the insertion and variant may influence the response and efficacy to novel EGFR targeted therapies. This study aims to fill this knowledge gap, by comprehensively characterising the epidemiology and clinical outcomes of Asian advanced EGFR exon 20 insertion mutated NSCLC patients.

Patients with cancers that are sensitive to radiotherapy treatment and/or patients who have experienced severe acute/ late side effects to radiotherapy will be recruited to the study. Blood and/or matched tumour-normal tissue pairs will be collected. Blood and/or tissue samples will be processed and studied for genetic and biochemical markers that have potential to be used for predicting sensitivity to radiation.

There is evidence for the effectiveness and feasibility of the individual components of TIER-HF-PC, however there is a need to test how these individual components interact to allow the researchers to deliver TIER-HF-PC as a model of care in its totality. In the short term, this study will assess if TIER-HF-PC is beneficial for patients and caregivers.