National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lun... | Recruiting
National Lung Matrix Trial: Multi-d... | Recruiting
National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer

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Medical Conditions
  • Non-Small Cell Lung Cancer
  • Carcinoma, Squamous Cell
  • Adenocarcinoma
Primary Contact Details
Recruitment Status
Recruiting
Trial source and source ID number
NCT02664935
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
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.
Research Details
  • 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.
Phase
Phase 2
Study Design
Sorry, this information is not available
Study Type
Interventional
Intervention
Drug : AZD4547, Drug : AZD2014, Drug : Palbociclib, Drug : Crizotinib, Drug : Selumetinib, Drug : Docetaxel, Drug : AZD5363, Drug : AZD9291, Drug : MEDI4736

Study Arm Groups : Arm A: AZD4547, Arm B: AZD2014, Arm C: Palbociclib, Arm D: Crizotinib, Arm E: Selumetinib & Docetaxel, Arm E: Selumetinib & Docetaxel, Arm F: AZD5363, Arm G: AZD9291, Arm NA Cohort NA1: MEDI4736

Intervention Type
See Interventions above
Primary Outcome Measures
    Best objective response rate (ORR); From baseline until disease progression, assessed up to 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.
Secondary Outcome Measures
    Best percentage change in sum of target lesion diameters (PCSD); From baseline until disease progression, assessed up to 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.; Overall survival time (OS); From time of commencement of trial treatment until date of death, assessed up to 18 months.; Toxicity (Adverse Event as per CTCAE criteria); From date of informed consent to trial treatment until 28 days after the last administration of the last treatment, assessed up to 18 months.
Publication(s)
Sorry, this information is not available
Result Reports
Check availability of results on the Clinicaltrials.gov website
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
All
Age Range
18 Years - N/A
Who Can Participate
Patients
Number of Participants
620
Participant Inclusion Criteria
    Inclusion Criteria:

    - Patients 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 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, if they have progressed within 6 months of completing their adjuvant treatment.

    - Patients will also be eligible without the necessity for first line regimen if they have relapsed within 6 months of completion of definitive chemoradiation.

    - 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 (see section 6.4 for definition of an adequate sample).

    - 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.

    - CT scan of head, chest and abdomen within 28 days of treatment demonstrating measurable disease as per RECIST version 1.1.

    - Adequate haematological function within 7 days of treatment.

    - Haemoglobin ≥ 90 g/L.

    - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.

    - Platelets ≥ 100 x 109/L.

    - 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).

    - Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN).

    - Alanine transferase (ALT) ≤ 2.5 x ULN.

    - Aspartate transferase (AST) ≤ 2.5 x ULN.

    - Adequate renal function within 7 days of treatment.

    - Creatinine clearance (CLcr) >50 ml/min (measured or calculated by Cockcroft and Gault equation).

    - Age ≥ 18 years.

    - Females must agree to use adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:

    - Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments

    - Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

    - Women aged under 50 years old would be consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution.

    - Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

    Exclusion Criteria:

    - Major surgery (excluding placement of vascular access), chemotherapy, radiotherapy, any investigational agents or other anti-cancer therapy within 4 weeks prior to treatment.

    - Nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) that would preclude adequate absorption.

    - Any psychological, familial, sociological or geographical condition hampering protocol compliance.

    - 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.

    - Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

    - Any unresolved toxicity of grade 2, 3 or 4 from previous treatment (excluding alopecia) at Registration (see CTCAE).

    - 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.

    - Patients with asymptomatic brain metastases picked up at screening CT scan are not excluded providing that in the view of the 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.

    - As judged by the 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.

    - Pregnant or breast-feeding women

    Cardiac exclusion criteria and performance status eligibility criteria are detailed within The National Lung Matrix Trial arm-specific eligibility criteria.
Participant Exclusion Criteria
This is in the inclusion criteria above
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
Southampton General Hospital
Southampton
England
SO16 6YD
Edinburgh Cancer Centre at Western General Hospital
Edinburgh
Scotland
EH4 2XU
Velindre Cancer Center at Velindre Hospital
Cardiff
Wales
CF14 2TL
GSK Investigational Site
Cambridge
CB2 0QQ
St. James University Hospital, Department of Neurology
Leeds
LS9 7TF
Newcastle upon Tyne
NE7 7DN
Royal Marsden Hospital - Sutton
London
England
SW3 6JJ
Glasgow
G12 0YN
Department of Immunology Mindelsohn Way Edgbaston
Birmingham
B15 2GW
Trial Contact(s)
Primary Trial Contact
Susie M Brown
01214147611
Other Trial Contacts
Dee Wherton
01214147611
Countries Recruiting
United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
National Lung Matrix Trial: Multi-drug, Genetic Marker-directed, Non-comparative, Multi-centre, Multi-arm Phase II Trial in Non-small Cell Lung Cancer
EudraCT Number
Not available for this trial
Funder(s)
  • Cancer Research UK
  • AstraZeneca
  • Pfizer
  • Experimental Cancer Medicine Centre Network
Other Study ID Numbers
RG_14-072
Sponsor(s)
University of Birmingham
Key Dates

Recruitment Start Date

Mar 2015

Recruitment End Date

Sep 2018

Trial Start Date
Date Not Available
Trial End Date
Date Not Available
Date added to source

05 Jan 2016

Date updated in source

24 Oct 2016