Non-small cell lung cancer Cancer Malignant neoplasm of bronchus and lung
Conditions
Interventions
Current intervention as of 12/06/2019:
1. Arm A - FGFR Inhibitor
AZD4547 - closed to recruitment
2. Arm B - MTORC1/2 Inhibitor
Vistusertib (AZD2014)
3. Arm C - CDK4/6 Inhibitor
Palbociclib
4. Arm D - ALK Inhibitor
Crizotinib
5. Arm E - MEK inhibitor in combination with Docetaxel
Selumetinib and Docetaxel
6. Arm F – AKT Inhibitor
AZD5363 - closed to recruitment
7. Arm G – EGFR mutation positive T790M+ Inhibitor
Osimertinib (AZD9291) - closed to recruitment
8. Arm H – Sitravatinib - closed to recruitment
9. Arm NA - Anti-PDL1
Durvalumab (MEDI4736) - closed to recruitment
10. Arm J - AZD6738 + Durvalumab (MEDI4736)
Previous intervention as of 14/03/2019:
1. Arm A - FGFR Inhibitor
AZD4547
2. Arm B - MTORC1/2 Inhibitor
Crizotinib
5. Arm E - MEK inhibitor in combination with Docetaxel
AZD5363
7. Arm G – EGFR mutation positive T790M+ Inhibitor
Osimertinib (AZD9291)
8. Arm H – Sitravatinib
9. Arm NA - Anti-PDL1
Durvalumab (MEDI4736)
Previous intervention as of 21/09/2016:
1. Arm A - FGFR Inhibitor
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 14/03/2019: Core inclusion criteria are presented below. Additional inclusion criteria apply to each arm and are presented in the relevant arm supplement in the trial protocol. 1. Prior anti-cancer treatment: 1.1. Patients who refuse any standard-of-care first-line therapy are eligible to receive National Lung Matrix Trial treatment as first-line therapy, providing they explicitly consent to this effect 1.2. Patients who have previously consented to and received standard-of-care first-line therapy must have completed all standard-of-care therapy that the treating oncologist thinks is appropriate. As a minimum patients must have failed one or more lines of treatment (either radiological documentation of disease progression or due to toxicity). Patients whose disease has increased in size but is not classed as progressive disease as per RECIST criteria, will be eligible. Patients with no change at all in dimension of disease (i.e. true stability) after first-line therapy will not be eligible. 1.3. Patients who have progressed after surgical resection and adjuvant therapy will be eligible for entry without the need for the administration of first-line metastatic therapy 1.4. Patients will also be eligible without the necessity for first line regimen if they have relapsed within 6 months of completion of definitive chemoradiation 2. Consented and provided an adequate specimen to adequately characterise the molecular genotype of the tumour in the molecular pre-screening according to the molecular exclusion rules 3. Histological or cytologically confirmed NSCLC stage III (not suitable for radical radiotherapy or surgery) or stage IV. This includes patients who may have abnormal histology, but IHC strongly support either squamous cell carcinoma (p63 positivity) or adenocarcinoma (Thyroid transcription factor 1 [TTF1] positivity). If a physician and pathologist are convinced after multi-disciplinary review that the patient has stage III or IV NSCLC but where all the IHC is negative and the morphology does not distinguish a specific sub-type, these patients will be eligible for non-histology specific cohorts. 4. CT or MRI scan of head, chest and abdomen within 28 days of treatment demonstrating measurable disease as per RECIST version 1.1. (The same imaging modality must be used throughout treatment). 5. Adequate haematological function within 7 days of treatment: 5.1. Haemoglobin =90 g/l 5.2.Absolute neutrophil count (ANC) =1.5 x 10(9)/l 5.3. Platelets =100 x 10(9)/l 6. Adequate hepatic function within 7 days of treatment in patients with no liver metastasis (see arm-specific entry criteria for adequate hepatic function in patients with liver metastases): 6.1. Total serum bilirubin =1.5 x upper limit of normal (ULN). (Note that this will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who may be allowed inclusion at the discretion of the local Investigator). 6.2. Alanine transferase (ALT) =2.5 x ULN 6.3. Aspartate transferase (AST) =2.5 x ULN 7. Adequate renal function within 7 days of treatment: 7.1. Creatinine clearance (CLcr) >50 ml/min (measured or calculated by Cockcroft and Gault equation). If calculated CLcr is 50 ml/min the patient is eligi
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 14/03/2019: Core exclusion criteria are presented below. Additional exclusion criteria apply to each arm and are presented in the relevant arm supplement in the trial protocol. 1. Major surgery (excluding placement of vascular access) within 4 weeks prior to treatment 2. Nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) that would preclude adequate absorption 3. Any psychological, familial, sociological or geographical condition hampering protocol compliance 4. Concurrent malignancies or invasive cancers diagnosed within past 3 years except for adequately treated basal cell carcinoma of the skin and in situ carcinoma of the uterine cervix 5. Judgement by the local Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements 6. Any unresolved toxicity of grade 2, 3 or 4 from previous treatment (excluding alopecia) at Registration (see CTCAE Toxicity Criteria Gradings) 7. Patients who have previous symptomatic brain metastases or spinal cord compression are excluded unless they have had adequate treatment, no evidence of progression or symptoms, and have had no requirement for steroid treatment in the previous 28 days before commencement of trial treatment 8. Patients with asymptomatic brain metastases picked up at screening CT scan are not excluded providing that in the view of the local Investigator they do not require immediate radiotherapy or surgical intervention, and have had no requirement for steroid treatment in the previous 28 days before commencement of trial treatment 9. As judged by the local Investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus. Screening for chronic conditions is not required. 10. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to registration) Cardiac exclusion criteria, performance status and prior treatment washout periods are detailed within the National Lung Matrix Trial arm-specific eligibility criteria. Previous exclusion criteria as of 12/12/2016: 1. Major surgery (excluding placement of vascular access) within 4 weeks prior to treatment 2. Nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) that would preclude adequate absorption 3. Any psychological, familial, sociological or geographical condition hampering protocol compliance. 4. Concurrent malignancies or invasive cancers diagnosed within past 3 years except for adequately treated basal cell carcinoma of the skin and in situ carcinoma of the uterine cervix 5. Judgement by the local investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements 6. Any unresolved toxicity of grade 2, 3 or 4 from previous treatment (excluding alopecia) at Registration. 7. Patients who have previous symptomatic brain metastases or spinal cord compression are excluded unless they have had adequate treatment, no evidence of progression or symptoms, and have had no requirement for steroid treatment in the previous 28 days before commencement of trial treatment 8. Patients with asymptomatic brain metastases picked up at screening CT scan are not excluded providing that in the view
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 14/03/2019: 1. Best percentage change in sum of target lesion diameters (PCSD) 2. Time to Progression (TTP) 3. Overall survival time (OS) 4. Adverse events (AE) Previous secondary outcome measures: 1. Best percentage change in sum of target lesion diameters (PCSD) 2. Overall survival time (OS) 3. Progression-free survival time (PFS) 4. Time to Progression (TTP) 5. Adverse events Added 14/02/2017: 6. Durable clinical benefit (DCB) | — |
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 14/03/2019; updated 12/06/2020 to add Arm J: 1. Objective response (OR) – Arms A, B, D, E, F, G, H, NA, J 2. Durable clinical benefit (DCB) – Arms A, B, D, E, F, H, NA, J 3. Progression-free survival time (PFS) – Arm C Previous primary outcome measures: Best objective response (BOR); Timepoint(s): Patients will have CT scans every 6 weeks from baseline until disease progression | — |
Countries
England, United Kingdom
Outcome results
None listed