Non-Small Cell Lung Cancer, Carcinoma, Squamous Cell, Adenocarcinoma
Conditions
Keywords
NSCLC, Lung Cancer, Adenocarcinoma, Matrix, SMP2, Umbrella Trial Design, Multi-arm
Brief 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.
Interventions
DRUGVistusertib
MTORC1/2 Inhibitor
DRUGPalbociclib
CDK4/6 Inhibitor
DRUGCrizotinib
ALK/MET/ROS1 Inhibitor
DRUGSelumetinib
MEK Inhibitor
DRUGDocetaxel
Taxane, anti-mitotic cytotoxic chemotherapy
DRUGAZD4547
FGFR Inhibitor
DRUGAZD5363
AKT Inhibitor
DRUGOsimertinib
EGFRm+ T790M+ Inhibitor
DRUGDurvalumab
Anti-PDL1
DRUGSitravatinib
VEGFR Inhibitor
DRUGAZD6738
ATR inhibitor
Sponsors
Cancer Research UK
AstraZeneca
Pfizer
Experimental Cancer Medicine Centres
Mirati Therapeutics Inc.
University of Birmingham
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Core inclusion and
Exclusion criteria
are presented below. Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response (OR) | From baseline until disease progression, assessed up to 18 months. | CT scans every 6 weeks from baseline until disease progression (Primary outcome for all Trial Arms except Arm C). Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months. |
| Progression-free survival time (PFS) | From date of commencement of trial treatment to date of CT scan when progressive disease first recorded or date of death without previously recorded progression, assessed up to 18 months. | Defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression (Primary Outcome for Arm C only). Patients who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression. Investigators expect patients to participate in the study for a maximum of 18 months, however, cannot guarantee that some patients may participate over 18 months. |
| Durable clinical benefit (DCB) | From baseline until the first scan after 24 weeks showing the patient free of disease progression. | A patient will be defined as experiencing DCB if they remain free of disease progression at their fourth CT or MRI scan since treatment start date, i.e. approximately 24 weeks, or at any scan after 24 weeks that shows the patient free of disease progression (co-primary outcome for all Trial Arms except Arm C & G) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best percentage change in sum of target lesion diameters (PCSD) | From baseline until disease progression, assessed up to 18 months. | At each evaluation, the longest diameters of all selected target lesions will be measured and summed and the percentage change from the baseline measurement will be calculated. The best percentage change is the one that reflects either the greatest decrease or the least increase over the whole period of assessment. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months. |
| Adverse Events (AE) | From date of informed consent to trial treatment until 28 days after the last administration of the last treatment, assessed up to 18 months. | Adverse events will be recorded in relation to each cycle of treatment and graded according to Common Terminology Criteria for Adverse Events (CTCAE). The incidence of each adverse event (all grades and grade 3/4) will be reported as a per-patient-cycle rate and as a per-patient rate. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months. |
| Time to Progression (TTP) | The time from commencement of trial treatment to the date of the CT scan when progressive disease first recorded, assessed up to 18 months. | This is defined as the time from commencement of trial treatment to the date of the CT scan when progressive disease first recorded. Patients with no recorded progression at the time of analysis or who die without recorded progression will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months. |
| Overall survival time (OS) | From time of commencement of trial treatment until date of death, assessed up to 18 months. | This is defined as the time of commencement of trial treatment to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months. |
Countries
United Kingdom
Outcome results
None listed