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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01970865




Registration number
NCT01970865
Ethics application status
Date submitted
16/10/2013
Date registered
28/10/2013

Titles & IDs
Public title
A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations
Scientific title
PHASE 1/2 STUDY OF PF-06463922 (AN ALK/ROS1 TYROSINE KINASE INHIBITOR) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER HARBORING SPECIFIC MOLECULAR ALTERATIONS
Secondary ID [1] 0 0
2013-002620-17
Secondary ID [2] 0 0
B7461001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - PF-06463922
Treatment: Drugs - Crizotinib

Experimental: PF-06463922 -

Other: Crizotinib - ALK+ NSCLC patients who are treatment naïve may be eligible to receive crizotinib following PF-06463922 as a substudy to the main study.


Treatment: Drugs: PF-06463922
Oral, starting dose 10mg once a day, dose escalation in Phase 1 until recommended Phase 2 dose determined, continuous daily dosing, cycles lasting 21 days

Treatment: Drugs: Crizotinib
Oral, starting dose of 250 mg BID continuous daily dosing every 21 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1
Timepoint [1] 0 0
Cycle 1 (21 days)
Primary outcome [2] 0 0
Percentage of Participants With Overall and Intracranial Objective Response (Phase 2)
Timepoint [2] 0 0
3 years
Secondary outcome [1] 0 0
Percentage of Participants With Overall and Intracranial Objective Response (Phase 1)
Timepoint [1] 0 0
From start of study treatment until CR or PR (maximum of 8 years approximately)
Secondary outcome [2] 0 0
Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)
Timepoint [2] 0 0
From start of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 8 years approximately)
Secondary outcome [3] 0 0
Number of Participants With Duration of Response (DOR) and Intracranial DOR (Phase 1)
Timepoint [3] 0 0
From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Secondary outcome [4] 0 0
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at 12 and 24 Weeks (Phase 1)
Timepoint [4] 0 0
12 and 24 weeks
Secondary outcome [5] 0 0
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
Progression-Free Survival (PFS) (Phase 1)
Timepoint [6] 0 0
From start of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 8 years approximately)
Secondary outcome [7] 0 0
Overall Survival (OS) (Phase 1)
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [8] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [9] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [9] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).
Secondary outcome [10] 0 0
Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [10] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [11] 0 0
Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [11] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).
Secondary outcome [12] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [12] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours post-dose on Day -7 for all other groups.
Secondary outcome [13] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [13] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [14] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [14] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [15] 0 0
Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [15] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [16] 0 0
Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [16] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [17] 0 0
Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [17] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [18] 0 0
Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [18] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [19] 0 0
Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)
Timepoint [19] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.
Secondary outcome [20] 0 0
Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)
Timepoint [20] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)
Secondary outcome [21] 0 0
Renal Clearance (CLr) of PF-06463922 (Phase 1)
Timepoint [21] 0 0
0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
Secondary outcome [22] 0 0
Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)
Timepoint [22] 0 0
0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15
Secondary outcome [23] 0 0
Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)
Timepoint [23] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [24] 0 0
Time for Cmax (Tmax) of Midazolam (Phase 1)
Timepoint [24] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [25] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)
Timepoint [25] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [26] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)
Timepoint [26] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [27] 0 0
Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)
Timepoint [27] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [28] 0 0
Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)
Timepoint [28] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [29] 0 0
Terminal Half-Life of Midazolam (Phase 1)
Timepoint [29] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [30] 0 0
Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 1)
Timepoint [30] 0 0
Screening (up to 28 days)
Secondary outcome [31] 0 0
Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 1)
Timepoint [31] 0 0
Screening (up to 28 days)
Secondary outcome [32] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)
Timepoint [32] 0 0
From start of study treatment until end of treatment (maximum of 8 years approximately)
Secondary outcome [33] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)
Timepoint [33] 0 0
From start of study treatment until end of treatment (maximum of 8 years approximately)
Secondary outcome [34] 0 0
Change From Baseline in Mini Mental State Examination (MMSE) Score (Phase 1)
Timepoint [34] 0 0
Baseline, Day 1 of Cycle 1-52, and end of treatment (up to 3 years)
Secondary outcome [35] 0 0
Time to Tumor Response (TTR) and Intracranial TTR (Phase 2 and DDI Sub-study)
Timepoint [35] 0 0
From first dose of study treatment to the first documentation of objective tumor response (CR or PR) (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [36] 0 0
Duration of Response (DOR) and Intracranial DOR (Phase 2 and DDI Substudy)
Timepoint [36] 0 0
From first dose of study treatment to first documentation of PD or to death due to any cause, whichever occurred first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [37] 0 0
Percentage of Participants Achieving Disease Control and Intracranial Disease Control at Week 12 and 24 (Phase 2 and DDI Substudy)
Timepoint [37] 0 0
Weeks 12 and 24
Secondary outcome [38] 0 0
Time to Progression on the Last Prior Therapy (Phase 2)
Timepoint [38] 0 0
From first dose of study treatment to the date of progression (maximum of 7.5 years for Phase 2)
Secondary outcome [39] 0 0
Time to Tumor Progression (TTP) and Intracranial TTP (Phase 2 and DDI Substudy)
Timepoint [39] 0 0
From first dose of study treatment to the first documentation of objective PD (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [40] 0 0
Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2)
Timepoint [40] 0 0
From first dose of study treatment until first event of CNS progression (maximum of 7.5 years for Phase 2)
Secondary outcome [41] 0 0
Progression-Free Survival (PFS) (Phase 2 and DDI Substudy)
Timepoint [41] 0 0
From first dose of study treatment to first documentation of objective PD or death due to any cause, whichever came first (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [42] 0 0
Overall Survival (Phase 2 and DDI Substudy)
Timepoint [42] 0 0
From first dose of study treatment until date of death (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [43] 0 0
Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2)
Timepoint [43] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [44] 0 0
Time for Cmax (Tmax) of PF-06463922 (Phase 2)
Timepoint [44] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [45] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2)
Timepoint [45] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Secondary outcome [46] 0 0
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2)
Timepoint [46] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [47] 0 0
Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2)
Timepoint [47] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [48] 0 0
Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2)
Timepoint [48] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Secondary outcome [49] 0 0
Terminal Half-Life of PF-06463922 (Phase 2)
Timepoint [49] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7
Secondary outcome [50] 0 0
Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2)
Timepoint [50] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [51] 0 0
Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2)
Timepoint [51] 0 0
Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15
Secondary outcome [52] 0 0
Number of Participants With ALK Mutation Based on Plasma CNA Analysis (Phase 2)
Timepoint [52] 0 0
Screening (up to 28 days)
Secondary outcome [53] 0 0
Number of Participants With ALK Mutation Based on Tumor Tissue Analysis (Phase 2)
Timepoint [53] 0 0
Screening (up to 28 days)
Secondary outcome [54] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2 and DDI Sub-study)
Timepoint [54] 0 0
From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [55] 0 0
Number of Participants Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2 and DDI Sub-study)
Timepoint [55] 0 0
From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [56] 0 0
Number of Participants With Treatment-Emergent Adverse Events (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [56] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [57] 0 0
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Hematology
Timepoint [57] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [58] 0 0
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Chemistry
Timepoint [58] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [59] 0 0
Number of Participants With Laboratory Abnormalities (Phase 1, Phase 2 and DDI Sub-study) - Coagulation, Lipids and Urinalysis
Timepoint [59] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [60] 0 0
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [60] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [61] 0 0
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [61] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [62] 0 0
Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
Timepoint [62] 0 0
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
Secondary outcome [63] 0 0
Number of Participants With Suicidal Ideation and Suicidal Behavior (Phase 2)
Timepoint [63] 0 0
From first dose of study treatment to end of treatment (maximum of 7.5 years for Phase 2)
Secondary outcome [64] 0 0
Change From Baseline in Total Scores for Beck Depression Inventory (BDI)-II (Mood Assessment) (Phase 2)
Timepoint [64] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [65] 0 0
Change From Baseline in Total Scores for Detection Test (Cognitive Function Assessment) (Phase 2)
Timepoint [65] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [66] 0 0
Change From Baseline in Total Scores for Identification Test (Cognitive Function Assessment) (Phase 2)
Timepoint [66] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [67] 0 0
Change From Baseline in Total Scores for One Back Test (Cognitive Function Assessment) (Phase 2)
Timepoint [67] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [68] 0 0
Change From Baseline in Total Scores for International Shopping List Test (Cognitive Function Assessment) (Phase 2)
Timepoint [68] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [69] 0 0
Change From Baseline in Total Scores for International Shopping List Test-Delayed Recall (Cognitive Function Assessment) (Phase 2)
Timepoint [69] 0 0
Baseline, Day 1 of Cycles 2-5, Day 1 of every other cycle from Cycle 6, and end of treatment (up to 3 years)
Secondary outcome [70] 0 0
Number of Participants With Absolute Values and Change From Baseline in PR Interval Meeting Pre-defined Criteria (Phase 2 and DDI Substudy)
Timepoint [70] 0 0
From first dose of study treatment to end of treatment maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)

Eligibility
Key inclusion criteria
Inclusion Criteria

* Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA) approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment.
* Disease Status Requirements:

Phase 1: ALK-positive NSCLC and ROS1-positive patients must either be treatment naïve in the advanced setting or have had disease progression after at least 1 previous ALK/ROS1 inhibitor therapy(ies).

Phase 2:

ALK-positive NSCLC patients must either be or have had:

* Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ALK inhibitor therapy allowed).
* Disease progression after crizotinib only. No prior chemotherapy is allowed in the metastatic disease setting.
* Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the metastatic disease setting.
* Disease progression after 1 prior ALK inhibitor therapy other than crizotinib. Patients may have had any number of prior chemotherapy regimens in any disease setting.
* Disease progression after 2 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting.
* Disease progression after 3 prior ALK inhibitor therapies. Patients may have had any number of prior chemotherapy regimens in any disease setting.

ROS1-positive NSCLC patients may be:

* Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ROS inhibitor therapy).
* Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies).

* Tumor Requirements:

All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks prior to study entry) will be eligible. Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) are eligible.

* Adequate Bone Marrow, Pancreatic Function, Renal Function and Liver Function.
* Negative Serum pregnancy test for females of childbearing potential
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
* Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
* Systemic anti cancer therapy completed within a minimum of 5 half lives of study entry.
* Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody.
* Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
* Clinically significant cardiovascular disease (that is, active or <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class = II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, or congenital long QT syndrome.
* History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis.
* Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are sensitive CYP2B6 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/05/2023
Sample size
Target
Accrual to date
Final
364
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Sydney Local Health District [rpa]
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Sydney Local Health District [rpa]
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
Belgium
State/province [13] 0 0
Edegem
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
France
State/province [16] 0 0
Grenoble Cedex 9
Country [17] 0 0
France
State/province [17] 0 0
Rennes Cedex 9
Country [18] 0 0
France
State/province [18] 0 0
Toulouse Cedex 9
Country [19] 0 0
France
State/province [19] 0 0
Villejuif Cedex
Country [20] 0 0
France
State/province [20] 0 0
Villejuif
Country [21] 0 0
Germany
State/province [21] 0 0
Cologne
Country [22] 0 0
Hong Kong
State/province [22] 0 0
Shatin
Country [23] 0 0
Italy
State/province [23] 0 0
Aviano (PN)
Country [24] 0 0
Italy
State/province [24] 0 0
Milano
Country [25] 0 0
Italy
State/province [25] 0 0
Perugia
Country [26] 0 0
Japan
State/province [26] 0 0
Aichi
Country [27] 0 0
Japan
State/province [27] 0 0
Chiba
Country [28] 0 0
Japan
State/province [28] 0 0
Ehime
Country [29] 0 0
Japan
State/province [29] 0 0
Hokkaido
Country [30] 0 0
Japan
State/province [30] 0 0
Hyogo
Country [31] 0 0
Japan
State/province [31] 0 0
Osaka
Country [32] 0 0
Japan
State/province [32] 0 0
Shizuoka
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo
Country [34] 0 0
Japan
State/province [34] 0 0
Fukuoka
Country [35] 0 0
Japan
State/province [35] 0 0
Koto-ku, Tokyo
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Singapore
State/province [37] 0 0
Singapore
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Navarra
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Switzerland
State/province [41] 0 0
Lausanne
Country [42] 0 0
Switzerland
State/province [42] 0 0
Winterthur
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01970865