Basket, umbrella, and platform trials

Trial designs that test one drug across many cancers (basket), many drugs in one cancer (umbrella), or keep adding arms over time (platform).

Enable tumour-agnostic approvals (NCI-MATCH, TAPUR), efficient biomarker-driven testing (Lung-MAP, I-SPY 2 in breast cancer), and adaptive randomisation (I-SPY 2 graduates drugs by predicted pCR).

Trials: what this kind of term is about · animated schematic, not to scale

Category

Trials

Key papers

rctNew England Journal of Medicine 2017changed practice

STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer

Men diagnosed with prostate cancer that has already spread, or that is locally advanced and high risk, should start abiraterone (or another androgen-receptor pathway inhibitor) at the same time as testosterone suppression rather than waiting for resistance. This roughly halves the risk of death over several years. The same platform later showed that docetaxel chemotherapy and, in high-volume metastatic disease, triple therapy also help, and that abiraterone benefits men with high-risk disease treated with radiotherapy.

Connected

technologies

2

Digital twins and virtual control arms N-of-1 and rapid platform trials

institutions

6

Garvan Institute of Medical Research / Kinghorn Cancer Centre Institut National du Cancer Korean Cancer Study Group Oslo University Hospital – The Norwegian Radium Hospital UCSF Helen Diller Family Comprehensive Cancer Center University College London Hospitals / UCL Cancer Institute

terms

5

Clinical trial Off-label Rare cancers Seamless, adaptive and Bayesian trial designs Single-arm trial

trials

2

myeloMATCH STAMPEDE

ideas

29

A DRUP-style protocol for off-label generic targeted drugs in rare tumours A global first-in-human network for academic cancer trials with single ethics review A multi-cancer platform trial of adaptive (dose-holiday) therapy A national platform trial that every ctDNA-positive patient can join A neutral platform trial for radiotherapy plus immunotherapy combinations A permanent neutral non-profit sponsor for multi-company platform trials A permanent platform trial for supportive-care interventions inside cooperative groups A perpetual platform trial in every major cancer, funded as infrastructure A platform trial of very-low-cost metronomic chemotherapy in LMIC common cancers A RECOVERY-style permanent platform trial of cheap drugs added to cancer care A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling A standing platform trial for every major cancer, funded as infrastructure A standing platform trial that assigns treatment by how the tumour escaped Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review Agree in advance how to borrow evidence between similar rare cancers Automated combination discovery: patient-sample screens feeding Bayesian platform trials Competing sponsors share one control arm in the same indication Just-in-time site activation: open a site in two weeks when a patient appears Let the trial learn: response-adaptive allocation across many combination arms Multi-arm, multi-stage trials to answer which order to give approved drugs One ethics approval and one consent form for a platform trial across countries One global rare cancer network with n-of-1 and Bayesian trial frameworks One master trial for cancer prevention drugs across many precancers One standing umbrella trial for all rare cancers in a country Pre-surgery platform trials that test combinations on pathological response in months Randomise inside the registry that already follows every patient Shared concurrent control arms across sponsors' trials in the same setting Standards for external control arms built from federated real-world data Trial-in-a-box: a preconfigured protocol kit any hospital can open for a rare cancer

collections

2

National Brain Tumor Society (NBTS)Pancreatic Cancer Action Network (PanCAN)

people

4

Angela DeMichele Laura J. Esserman Nicholas James Zhi-Ming Shao

bottlenecks

4

Rare and paediatric cancers without markets Too many combinations to test Trial design, endpoints and cost Trials enrol too few, too slowly

key papers

1

STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer