A Practical Guide to Designing Phase II Trials in Oncology -- Contents -- Contributors -- Foreword I -- Foreword II -- Preface -- 1 Introduction -- 1.1 The role of phase II trials in cancer -- 1.2 The importance of appropriate phase II trial design -- 1.3 Current use of phase II designs -- 1.4 Identifying appropriate phase II trial designs -- 1.5 Potential trial designs -- 1.6 Using the guidance to design your trial -- 2 Key points for consideration -- 2.1 Stage 1 - Trial questions -- 2.1.1 Therapeutic considerations -- 2.1.2 Primary intention of trial -- 2.1.3 Number of experimental treatment arms -- 2.1.4 Primary outcome of interest -- 2.2 Stage 2 - Design components -- 2.2.1 Outcome measure and distribution -- 2.2.2 Randomisation -- 2.2.3 Design category -- 2.3 Stage 3 - Practicalities -- 2.3.1 Practical considerations -- 2.4 Summary -- 3 Designs for single experimental therapies with a single arm -- 3.1 One-stage designs -- 3.1.1 Binary outcome measure -- 3.1.2 Continuous outcome measure -- 3.1.3 Multinomial outcome measure -- 3.1.4 Time-to-event outcome measure -- 3.1.5 Ratio of times to progression -- 3.2 Two-stage designs -- 3.2.1 Binary outcome measure -- 3.2.2 Continuous outcome measure -- 3.2.3 Multinomial outcome measure -- 3.2.4 Time-to-event outcome measure -- 3.2.5 Ratio of times to progression -- 3.3 Multi-stage designs -- 3.3.1 Binary outcome measure -- 3.3.2 Continuous outcome measure -- 3.3.3 Multinomial outcome measure -- 3.3.4 Time-to-event outcome measure -- 3.3.5 Ratio of times to progression -- 3.4 Continuous monitoring designs -- 3.4.1 Binary outcome measure -- 3.4.2 Continuous outcome measure -- 3.4.3 Multinomial outcome measure -- 3.4.4 Time-to-event outcome measure -- 3.4.5 Ratio of times to progression -- 3.5 Decision-theoretic designs -- 3.5.1 Binary outcome measure -- 3.5.2 Continuous outcome measure.

3.5.3 Multinomial outcome measure -- 3.5.4 Time-to-event outcome measure -- 3.5.5 Ratio of times to progression -- 3.6 Three-outcome designs -- 3.6.1 Binary outcome measure -- 3.6.2 Continuous outcome measure -- 3.6.3 Multinomial outcome measure -- 3.6.4 Time-to-event outcome measure -- 3.6.5 Ratio of times to progression -- 3.7 Phase II/III designs -- 4 Designs for single experimental therapies including randomisation -- 4.1 One-stage designs -- 4.1.1 Binary outcome measure -- 4.1.2 Continuous outcome measure -- 4.1.3 Multinomial outcome measure -- 4.1.4 Time-to-event outcome measure -- 4.1.5 Ratio of times to progression -- 4.2 Two-stage designs -- 4.2.1 Binary outcome measure -- 4.2.2 Continuous outcome measure -- 4.2.3 Multinomial outcome measure -- 4.2.4 Time-to-event outcome measure -- 4.2.5 Ratio of times to progression -- 4.3 Multi-stage designs -- 4.3.1 Binary outcome measure -- 4.3.2 Continuous outcome measure -- 4.3.3 Multinomial outcome measure -- 4.3.4 Time-to-event outcome measure -- 4.3.5 Ratio of times to progression -- 4.4 Continuous monitoring designs -- 4.4.1 Binary outcome measure -- 4.4.2 Continuous outcome measure -- 4.4.3 Multinomial outcome measure -- 4.4.4 Time-to-event outcome measure -- 4.4.5 Ratio of times to progression -- 4.5 Three-outcome designs -- 4.5.1 Binary outcome measure -- 4.5.2 Continuous outcome measure -- 4.5.3 Multinomial outcome measure -- 4.5.4 Time-to-event outcome measure -- 4.5.5 Ratio of times to progression -- 4.6 Phase IIIII designs -- 4.6.1 Binary outcome measure -- 4.6.2 Continuous outcome measure -- 4.6.3 Multinomial outcome measure -- 4.6.4 Time-to-event outcome measure -- 4.6.5 Ratio of times to progression -- 4.7 Randomised discontinuation designs -- 4.7.1 Binary outcome measure -- 4.7.2 Continuous outcome measure -- 4.7.3 Multinomial outcome measure -- 4.7.4 Time-to-event outcome measure.

4.7.5 Ratio of times to progression -- 5 Treatment selection designs -- 5.1 Including a control arm -- 5.1.1 One-stage designs -- 5.1.2 Two-stage designs -- 5.1.3 Multi-stage designs -- 5.1.4 Continuous monitoring designs -- 5.1.5 Decision-theoretic designs -- 5.1.6 Three-outcome designs -- 5.1.7 Phase II/III designs - same primary outcome measure at phase II and phase III -- 5.1.8 Phase II/III designs - different primary outcome measures at phase II and phase III -- 5.1.9 Randomised discontinuation designs -- 5.2 Not including a control arm -- 5.2.1 One-stage designs -- 5.2.2 Two-stage designs -- 5.2.3 Multi-stage designs -- 5.2.4 Continuous monitoring designs -- 5.2.5 Decision-theoretic designs -- 5.2.6 Three-outcome designs -- 5.2.7 Phase II/III designs - same primary outcome measure at phase II and phase III -- 5.2.8 Randomised discontinuation designs -- 6 Designs incorporating toxicity as a primary outcome -- 6.1 Including a control arm -- 6.1.1 One-stage designs -- 6.1.2 Two-stage designs -- 6.1.3 Multi-stage designs -- 6.2 Not including a control arm -- 6.2.1 One-stage designs -- 6.2.2 Two-stage designs -- 6.2.3 Multi-stage designs -- 6.2.4 Continuous monitoring designs -- 6.3 Toxicity alone -- 6.3.1 One stage -- 6.3.2 Continuous monitoring -- 6.4 Treatment selection based on activity and toxicity -- 6.4.1 Two-stage designs -- 6.4.2 Multi-stage designs -- 6.4.3 Continuous monitoring designs -- 7 Designs evaluating targeted subgroups -- 7.1 One-stage designs -- 7.1.1 Binary outcome measure -- 7.2 Two-stage designs -- 7.2.1 Binary outcome measure -- 7.3 Multi-stage designs -- 7.3.1 Binary outcome measure -- 7.3.2 Time-to-event outcome measure -- 7.4 Continuous monitoring designs -- 7.4.1 Binary outcome measure -- 7.4.2 Time-to-event outcome measure -- 8 'Chemo-radio-sensitisation' in head and neck cancer -- Stage 1 - Trial questions.

Therapeutic considerations -- Primary intention of trial -- Number of experimental treatment arms -- Primary outcome of interest -- Stage 2 - Design components -- Outcome measure and distribution -- Randomisation -- Design category -- Possible designs -- Stage 3 - Practicalities -- Practical considerations for selecting between designs -- Proposed trial design -- Summary -- 9 Combination chemotherapy in second-line treatment of non-small cell lung cancer -- Stage 1 - Trial questions -- Therapeutic considerations -- Primary intention of trial -- Number of experimental treatment arms -- Primary outcome of interest -- Stage 2 - Design components -- Outcome measure and distribution -- Randomisation -- Design category -- Possible designs -- Stage 3 - Practicalities -- Practical considerations for selecting between designs -- Proposed trial design -- Summary -- 10 Selection by biomarker in prostate cancer -- Stage 1 - Trial questions -- Therapeutic considerations -- Primary intention of trial -- Number of experimental treatment arms -- Primary outcome of interest -- Stage 2 - Design components -- Outcome measure and distribution -- Randomisation -- Design category -- Possible designs -- Stage 3 - Practicalities -- Practical considerations for selecting between designs -- Proposed trial design -- Summary -- 11 Dose selection in advanced multiple myeloma -- Stage 1 - Trial questions -- Therapeutic considerations -- Primary intention of trial -- Number of experimental arms -- Primary outcome of interest -- Stage 2 - Design components -- Outcome measure and distribution -- Randomisation -- Design category -- Possible designs -- Stage 3 - Practicalities -- Practical considerations for selecting between designs -- Proposed trial design -- Summary -- 12 Targeted therapy for advanced colorectal cancer -- Stage 1 - Trial questions -- Therapeutic considerations.

Primary intention of trial -- Number of experimental treatment arms -- Primary outcome of interest -- Stage 2 - Design components -- Outcome measure and distribution -- Randomisation -- Design category -- Possible designs -- Stage 3 - Practicalities -- Practical considerations for selecting between designs -- Proposed trial design -- Summary -- 13 Phase II oncology trials: Perspective from industry -- 13.1 Introduction -- 13.2 Commercial challenges, drivers and considerations -- 13.3 Selecting designs by strategy -- 13.3.1 Basic strategies addressed by phase II studies -- 13.3.2 Potential registration -- 13.3.3 Exploratory activity -- 13.3.4 Regimen selection -- 13.3.5 Phase II to support predicting success in phase III -- 13.3.6 Phase II safety trials -- 13.3.7 Prospective identification of target populations -- 13.4 Discussion -- References -- Index -- Statistics in Practice.