NCT02664935

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer

National Lung Matrix Trial: Multi-drug, Genetic Marker-directed, Non-comparative, Multi-centre, Multi-arm Phase II Trial in Non-small Cell Lung Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 423 (actual)
• Sponsor: University of Birmingham · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The trial consists of a series of parallel multi-centre single arm phase II trial arms, each testing an experimental targeted drug in a population stratified by multiple pre-specified actionable target putative biomarkers. The primary objective is to evaluate whether there is a signal of activity in each drug-(putative)biomarker cohort separately. A Bayesian adaptive design is adopted to achieve this objective and statistical details are given in the Protocol.

Detailed description

The trial is primarily an enrichment putative biomarker design, including patients who are positive for at least one of the actionable targets included in the trial. Patients who are positive for just one putative biomarker will receive the experimental targeted drug specific for that putative biomarker. Putative biomarkers within each drug cohort have been chosen such that in the majority of cases it is not expected that patients will be positive for two or more putative biomarkers within the same drug. In the rare situation that patients are positive for two or more putative biomarkers relevant across different drugs, treatment will be allocated in accordance with the following strategy: * All amplifications and rearrangements will be treated with targeted agent appropriate to them irrespective of concomitant mutations. This will yield crucial predictive biomarker information. * For concomitant mutations decisions will be made by the Chief Investigator on a case-by-case basis and based on close consideration of pathway preference and likely dominance of one signal pathway over another together with any pre-clinical efficacy studies that address the activity of the drugs in the presence of concomitant mutations. A trumping strategy has been devised for this purpose.

Conditions

• Non-Small Cell Lung Cancer
• Carcinoma, Squamous Cell
• Adenocarcinoma

Interventions

Type	Name	Description
DRUG	AZD4547	FGFR Inhibitor
DRUG	Vistusertib	MTORC1/2 Inhibitor
DRUG	Palbociclib	CDK4/6 Inhibitor
DRUG	Crizotinib	ALK/MET/ROS1 Inhibitor
DRUG	Selumetinib	MEK Inhibitor
DRUG	Docetaxel	Taxane, anti-mitotic cytotoxic chemotherapy
DRUG	AZD5363	AKT Inhibitor
DRUG	Osimertinib	EGFRm+ T790M+ Inhibitor
DRUG	Durvalumab	Anti-PDL1
DRUG	Sitravatinib	VEGFR Inhibitor
DRUG	AZD6738	ATR inhibitor

Timeline

• Start date: 2015-05-01
• Primary completion: 2025-09-01
• Completion: 2025-09-01
• First posted: 2016-01-27
• Last updated: 2025-05-21

Locations

25 sites across 1 country: United Kingdom