Table 1.
Summary of each trial's key characteristics.
| Trial | Disease | Primary endpoint(s) | Number of arms | Trial design | Type of biomarker(s) | Role of biomarker(s) | Responsibility for overall management | Primary funding source(s) | Challenges |
|---|---|---|---|---|---|---|---|---|---|
| NLMT | Advanced non-small cell lung cancer | Best objective response; Durable clinical benefit; Progression-free survival time | 8 | Bayesian adaptive umbrella design | Genetic markers | To determine arm/treatment allocation | Early Drug Development (EDD) Trial Management Team based within the Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham | Cancer Research UK | Uncertainty regarding total costs of trial – resolved by submitting estimated future costs and CRUK providing agreement in principle; additional costs of biomarker analysis – resolved by funding molecular screening platform as separate entity; significant dropout due to recruiting patients with advanced disease; CTU personnel required to interpret biomarker reports themselves to determine relevant treatment arm |
| TOPARP | Metastatic castration resistant prostate cancer | Treatment response according to pre-specified criteria | TOPARP-A: single arm TOPARP-B: two-arm randomised |
TOPARP- A: Open-label, single arm, two part adaptive design phase II trial. TOPARP-B: Open-label, two-arm randomised, each arm with a single stage phase II design. |
Genetic markers | TOPARP-A: Biomarker development - to identify predictive biomarkers of response to olaparib TOPARP B: Biomarker validation - biomarker guided patient selection for eligibility to confirm sub-group identified in A |
Institute of Cancer Research, UK | Trial run under the NCRN-AZ initiative (CRUK and AZ funded) | Complex sampling collection and processing requirements outside standard pathway at sites. QA sample failures at central labs which lead to delays in biomarker results being available; Greater CTU and lab activity/resource required to manage challenges and ensure collaborators' expectations were met. |
| ATLANTIS | Metastatic urothelial cancer | Progression-free survival | 3 | Adaptive multi-arm design | Homologous recombination deficiency and genetic markers | To determine arm/randomisation treatment | Clinical Trials Unit, University of Glasgow | Cancer Research UK | |
| PRIMUS001 | Metastatic pancreatic cancer | Progression-free survival | 2 | Adaptive design | Genetic markers | For subgroup analysis of primary outcome, and to determine eligibility for recruitment following interim analyses | Clinical Trials Unit, University of Glasgow | Cancer Research UK | |
| SALONICA | Ovarian cancer | Progression-free survival | 1 | Sequence of single arm trials, but plans to progress to Bayesian adaptive randomised design | Genetic markers | Initially for subgroup analysis, and then to determine randomisation ratio | Clinical Trials Unit, University of Glasgow | N/A – planning stage | |
| TASTER | Chronic Myeloid Leukaemia | Progression-free survival | 1 | Series of single arm trials | Biomarkers contributing to molecular signatures | To determine eligibility for which single arm trial | Clinical Trials Unit, University of Glasgow | N/A – planning stage | |
| POETIC | Breast cancer | Relapse free survival | 2 | Two-arm parallel randomised controlled trial | Genetic marker and Gene expression profile | To determine eligibility and for subgroup analyses | Institute of Cancer Research, UK | Cancer Research UK | |
| FOCUS 4 | Metastatic colorectal cancer | Progression-free survival | 3 molecularly stratified trials and 1 non-stratified trial | Multi-arm, multi-stage umbrella design | Genetic markers | To determine arm/randomisation treatment | MRC Clinical Trials Unit at UCL | NIHR/MRC EME Programme and Cancer Research UK | Intensive CTU resource requirements for the multi-tasking aspects of the adding and dropping arms design; High costs of running trial – resolved by securing joint funding between MRC/NIHR EME and Cancer Research UK and having trial conducted in a CTU with separate core funding; Delays in biomarker results turnaround and failed samples; Pathology number discrepancies; Failure to send GCP compliant documents from pathology lab to CTU; Needing comparison-specific CRFs therefore sites having to deal with several separate databases; |
| EU-PACT | Atrial fibrillation and venous thromboembolism | Time in therapeutic INR range during first three months of treatment | 2 | Two-arm parallel randomised controlled trial | Genetic markers | Predict therapeutic dose | Wolfson Centre for Personalised Medicine, University of Liverpool | European Commission Seventh Framework Programme | Need for rapid turnaround of genotyping results to allow same-day treatment initiation at predicted dose – resolved by working with industrial collaborator to develop efficient point of care test |