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

Sponsor
University of Birmingham
Study ID
NCT02664935
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
May 13, 2015
Status verified
Apr 2026
Primary completion
Nov 29, 2023
Completion
Nov 29, 2023

Study Design

Enrollment
423 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A: AZD4547
    AZD4547 - FGFR Inhibitor Route \& Formulation: Oral, Tablets Strengths: 20 \& 80mg Trial Dose \& Schedule: 80 mg BD, Continuous dosing, 21 day cycle.
  • Experimental: Arm B: Vistusertib (AZD2014)
    Vistusertib (AZD2014) - MTORC1/2 Inhibitor Route \& Formulation: Oral, Tablets Strengths: 25mg Trial Dose \& Schedule: 125 mg BD, Intermittent dosing (2 continuous days in 7), 28 day cycle.
  • Experimental: Arm C: Palbociclib
    Palbociclib - CDK4/6 Inhibitor Route \& Formulation: Oral, Capsules Strengths: 75, 100 \& 125mg Trial Dose \& Schedule: 125 mg OD, Intermittent dosing (21 days on, 7 days off), 28 day cycle.
  • Experimental: Arm D: Crizotinib
    Crizotinib - ALK Inhibitor Route \& Formulation: Oral, Capsules Strengths: 200 \& 250mg Trial Dose \& Schedule: 250 mg BD, Continuous dosing, 21 day cycle.
  • Experimental: Arm E: Selumetinib & Docetaxel
    AZD6244 (Selumetinib) - MEK Inhibitor Route \& Formulation: Oral, Capsules Strengths: 25mg Trial Dose \& Schedule: 75 mg BD, Continuous dosing, 21 day cycle. Docetaxel - Chemotherapy Route \& Formulation: IV infusion over 30-60 minutes, concentrate for solution for infusion. Trial Dose \& Schedule: 75 mg/m2, 3-weekly, 21 day cycle.
  • Experimental: Arm F: AZD5363
    AZD5363 - AKT Inhibitor Route \& Formulation: Oral, Tablets Strengths: 80 \& 200mg Trial Dose \& Schedule: 480 mg BD, Intermittent dosing (4 days on, 3 days off), 28 day cycles.
  • Experimental: Arm G: Osimertinib (AZD9291)
    Osimertinib (AZD9291) - EGFRM+ and T790M+ Inhibitor Route \& Formulation: Oral, Tablets Strengths: 80mg Trial Dose \& Schedule: 80 mg OD, Continuous dosing, 21 day cycles.
  • Experimental: Arm NA: Durvalumab (MEDI4736)
    Durvalumab (MEDI4736) - Anti-PDL1 Route \& Formulation: IV Infusion, Lyophilized powder for solution for infusion Strengths: Vial containing 200mg Trial Dose \& Schedule: 10 mg/kg IV, 2-weekly.
  • Experimental: Arm H: Sitravatinib
    Sitravatinib - VEGFR Inhibitor Route \& Formulation: Oral, Capsules Strengths: 10 \& 40mg Trial Dose \& Schedule: 120 mg OD, Continuous dosing, 21 day cycles.
  • Experimental: Arm J: AZ6738 & Durvalumab
    AZD6738 - ATR Inhibitor Route \& Formulation: Oral, Tablets Strengths: 20mg, 80mg, 100mg Trial Dose \& Schedule: 240 mg twice daily (BD) on days 15-28 of 28 day cycle. Durvalumab (MEDI4736) - Anti-PDL1 Route \& Formulation: IV Infusion, Lyophilized powder for solution for infusion Strengths: Vial containing 500mg Trial Dose \& Schedule: 1500mg on day 1 of each 28 day cycle

Primary Outcome Measure

Objective response (OR) [ Time Frame: From baseline until disease progression, assessed up to 18 months. ]

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