History of Changes for Study: NCT01970865

A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations

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Study Record Versions

Version	Submitted Date	Changes
1	October 22, 2013	None (earliest Version on record)
2	November 20, 2013	Study Status
3	December 16, 2013	Study Status
4	January 14, 2014	Study Status
5	January 24, 2014	Recruitment Status, Study Status and Contacts/Locations
6	February 24, 2014	Study Status and Contacts/Locations
7	March 25, 2014	Study Status
8	April 29, 2014	Outcome Measures, Study Status, Contacts/Locations and Eligibility
9	May 28, 2014	Study Status and Contacts/Locations
10	June 24, 2014	Study Status
11	July 11, 2014	Study Status
12	August 7, 2014	Study Status
13	September 9, 2014	Study Status
14	October 30, 2014	Study Status, Contacts/Locations, Study Design and Study Identification
15	November 4, 2014	Study Status
16	November 17, 2014	Outcome Measures, Contacts/Locations, Eligibility, Study Design, Study Status and Study Identification
17	December 12, 2014	Contacts/Locations, Study Status and Study Identification
18	January 9, 2015	Study Status and Contacts/Locations
19	February 9, 2015	Study Status, Contacts/Locations and Study Design
20	March 13, 2015	Study Status, Contacts/Locations and Study Design
21	March 19, 2015	Study Design and Study Status
22	April 13, 2015	Contacts/Locations and Study Status
23	May 13, 2015	Study Status and Contacts/Locations
24	June 8, 2015	Contacts/Locations and Study Status
25	July 1, 2015	Study Status, Contacts/Locations and Study Identification
26	July 29, 2015	Contacts/Locations and Study Status
27	August 20, 2015	Contacts/Locations, Outcome Measures, Study Status, Study Design, Arms and Interventions, Eligibility, Conditions and Study Identification
28	September 18, 2015	Contacts/Locations, Study Status, Eligibility and Outcome Measures
29	October 5, 2015	Contacts/Locations, Study Status, Eligibility and Study Design
30	November 4, 2015	Contacts/Locations, Study Design, Study Status and Eligibility
31	December 1, 2015	Contacts/Locations, Study Status and Outcome Measures
32	December 10, 2015	Contacts/Locations, Study Status and Study Identification
33	January 20, 2016	Contacts/Locations, Study Status and Study Identification
34	February 6, 2016	Contacts/Locations, Study Status and Study Identification
35	March 9, 2016	Contacts/Locations, Study Status and Study Identification
36	March 25, 2016	Contacts/Locations, Study Design, Study Status and Study Identification
37	April 1, 2016	Contacts/Locations, Study Status and Eligibility
38	May 1, 2016	Contacts/Locations and Study Status
39	May 26, 2016	Study Status and Contacts/Locations
40	June 15, 2016	Contacts/Locations and Study Status
41	July 7, 2016	Contacts/Locations and Study Status
42	July 26, 2016	Contacts/Locations, Study Design, Study Status and Study Identification
43	August 12, 2016	Contacts/Locations, Study Design, Study Status and Study Identification
44	September 12, 2016	Contacts/Locations and Study Status
45	October 5, 2016	Study Status and Study Identification
46	November 3, 2016	Study Status and Study Identification
47	November 20, 2016	Study Design, Study Status and Study Identification
48	December 12, 2016	Study Status
49	January 12, 2017	Contacts/Locations, Study Design, Study Status and Study Identification
50	January 14, 2017	Contacts/Locations, Study Status and Study Identification
51	January 30, 2017	Contacts/Locations and Study Status
52	February 23, 2017	Contacts/Locations and Study Status
53	March 14, 2017	Study Status and Contacts/Locations
54	April 4, 2017	Study Status and Contacts/Locations
55	April 10, 2017	Study Status
56	May 1, 2017	Contacts/Locations and Study Status
57	May 18, 2017	Study Status and Contacts/Locations
58	June 6, 2017	Study Status and Contacts/Locations
59	June 29, 2017	Contacts/Locations and Study Status
60	July 24, 2017	Study Status and Contacts/Locations
61	August 17, 2017	Study Status
62	September 11, 2017	Study Status
63	September 28, 2017	Study Status
64	October 25, 2017	Recruitment Status, Study Status, Contacts/Locations and Study Design
65	November 6, 2017	Contacts/Locations, Study Status and Study Design
66	November 21, 2017	Study Status
67	January 29, 2018	Study Status and Study Design
68	February 12, 2018	Study Status and Study Design
	Results Submission Events
March 5, 2018		Returned after QC review: March 30, 2018
69	May 8, 2018	Study Status, Outcome Measures, Document Section, Results and Contacts/Locations
70	May 30, 2018	Study Status and Contacts/Locations
71	August 22, 2018	Study Status
72	November 29, 2018	Study Status and Study Design
73	January 1, 2019	Study Status
74	April 29, 2019	Study Status, Contacts/Locations, IPDSharing and Study Identification
75	October 23, 2019	Contacts/Locations and Study Status
76	July 2, 2020	Study Status, Outcome Measures
77	February 18, 2021	Study Status, Contacts/Locations and Study Design
78	November 4, 2021	Study Status
79	February 16, 2022	Study Status
80	October 24, 2022	Study Status
81	January 9, 2023	Study Status, Contacts/Locations and Study Design
82	March 16, 2023	Study Status and Contacts/Locations
83	June 5, 2023	Recruitment Status, Study Status and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	B7461001
Brief Title:	A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations
Official 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 IDs:

Study Status


Record Verification:	October 2013
Overall Status:	Not yet recruiting
Study Start:	November 2013
Primary Completion:	December 2017 [Anticipated]
Study Completion:	December 2017 [Anticipated]

First Submitted:	October 16, 2013
First Submitted that Met QC Criteria:	October 22, 2013
First Posted:	October 28, 2013 [Estimate]

Last Update Submitted that Met QC Criteria:	October 22, 2013
Last Update Posted:	October 28, 2013 [Estimate]

Sponsor/Collaborators


Sponsor:	Pfizer
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	No

Study Description


Brief Summary:	Phase 1 and 2 trial to study the safety, pharmacokinetics, pharmacodynamics, patient reported outcomes and efficacy of PF-06463922 in ALK + advanced non-small cell lung cancer patients and ROS1+ advanced non small cell lung cancer patients .
Detailed Description:

Conditions


Conditions:	ALK Positive Non Small Cell Lung Cancer
Keywords:	Phase 1 Phase 2 safety pharmacokinetic pharmacodynamic efficacy

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Single Group Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	200 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: PF-06463922	Drug: 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

Outcome Measures


Primary Outcome Measures:
1.	Number of patients with Dose-limiting toxicities (DLT) [ Time Frame: First Cycle ]
2.	Percentage of Patients With Overall and Intracranial Objective Response [ Time Frame: Every 6 weeks from the time of patient enrollment up to 4 years ] Percentage of patients with OR based assessment of intracranial and overall confirmed complete remission (CR) or confirmed partial remission (PR) according to a modified Response Evaluation Criteria in Solid Tumors (RECIST)v 1.1.
Secondary Outcome Measures:
1.	Maximum tolerated dose and recommended phase 2 dose [ Time Frame: At end of cycle 1 ] Recommended phase 2 dose will be determined after the last patient has been treated for at least one cycle in the Phase 1
2.	Change from Baseline in Mini Mental State Examination (MMSE) across treatment cycles [ Time Frame: Every 3 weeks from the time of enrollment up to 4 years ] MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranges from 0 to 30, higher score indicates better cognitive state. Change: across treatment cycles
3.	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 7 days prior to first dose of treatment ] Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
4.	Volume of Distribution at Steady State (Vss) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose of treatment ] Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
5.	Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ]
6.	Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ]
7.	Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose of treatment ]
8.	Apparent Volume of Distribution (Vz/F) [ Time Frame: 7 days prior to the first dose of treatment ] Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
9.	Plasma Decay Half-Life (t1/2) [ Time Frame: 7 days prior to the first dose of treatment ] Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
10.	Urine clearance of drug (Clr) for subjects in food effect and Midazolam substudy [ Time Frame: Pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ]
11.	Urine Ae% for subjects in food effect and Midazolam substudy [ Time Frame: Pre Cycle 1 Day 15 dose of treatment ]
12.	Maximum Observed Plasma Concentration (Cmax) for subjects in Midazolam substudy [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ]
13.	Time to Reach Maximum Observed Plasma Concentration (Tmax) for subjects in Midazolam substudy [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ]
14.	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for subjects in Midazolam substudy [ Time Frame: 7 days prior to first dose and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ] Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) after administration of MDZ
15.	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ] AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).
16.	Plasma Decay Half-Life (t1/2) for subjects in Midazolam substudy [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ] Plasma decay half-life is the time measured for the plasma concentration to decrease by one half after administration of MDZ
17.	Apparent Oral Clearance (CL/F) for subjects in Midazolam substudy [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ] Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood after administration of MDZ
18.	Apparent Oral Clearance (CL/F) [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ] Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
19.	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 7 days prior to the first dose of treatment ] Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
20.	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] [ Time Frame: 7 days prior to the first dose of treamtent ] AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).
21.	Drug concentration in cerebral spinal fluid (CSF) [ Time Frame: Optional sample, up to 4 years, if patient undergoes a lumbar puncture ] Should CSF specimen be taken for suspected tumor infiltration this sample may be used for drug concentration levels
22.	Selective molecular profiling of circulating nucleic acids (CNA) [ Time Frame: Within 28 days of first dose of treatment and at 28 days after the last dose of treatment ] Selective molecular profiling of circulating nucleic acids (CNA) at the end of treatment visit defined as 28 days after the last treatment administration
23.	Selective molecular profiling of tumor tissue [ Time Frame: Within 28 days prior to first dose of treatment ] Blood specimen optimized for plasma preparation for nucleic acid analysis will be collected at screening and at end of treatment
24.	Circulating tumor cells (CTC) enumeration and molecular characterization [ Time Frame: Prior to treatment start on Cycle 1 Day 1, at the end of Cycle 2 and at 28 days after the last dose of treatment ]
25.	QTc interval [ Time Frame: Within 28 days prior to first dose of treatment, 7 days prior to the first dose of treatment and Day 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-5 and 28 days after the last dose of treatment ] ECGs performed to assess QTc (msec) at baseline and on study treatment and at the end of treatment visit defined as 28 days after the last treatment administration
26.	Patient reported Outcomes [ Time Frame: Day 1 of every cycle, pre dose, up to 4 years and at 28 days after the last dose of treatment ] To assess impact of disease /treatment related symptoms of lung cancer and quality of life at D1 of every cycle and at the end of treatment visit defined as 28 days after the last treatment administration
27.	Duration of Response (DR) [ Time Frame: Every 6 weeks from the time of enrollment up to 4 years ] Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
28.	Progression-Free Survival (PFS) [ Time Frame: Every 6 weeks from the time of enrollment to the first documented progression or date of death from any cause, assessed up to 4 years ] The period from study entry until disease progression, death or date of last contact.
29.	Overall Survival (OS) [ Time Frame: From the time of enrollment until the date of death from any causes, up to 4 years ] Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
30.	Disease Control Rate (DCR) [ Time Frame: Every 6 weeks from the time of enrollment up to 4 years ] DCR is defined as the percent of patients with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1, at 6 weeks.
31.	Disease Control Rate (DCR) [ Time Frame: Every 12 weeks from the time of enrollment up to 4 years ] DCR is defined as the percent of patients with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.1, at 12 weeks
32.	Left Ventricular Ejection Fraction (LVEF) [ Time Frame: Within 28 days prior to the first dose of treatment, pre dose on Day 1 of Cycle 2, pre dose on Day 1 of Cycle 3, pre dose on Day 1 of Cycle 5 and pre dose on Day 1 of every 2 Cycles thereafter; and at 28 days after the last dose of treatment ] Left Ventricular Ejection Fraction percentage change by echocardiogram or by multigated acquisition gated scan (MUGA)
33.	Apparent Volume of Distribution (Vz/F) for subjects in Midazolam substudy [ Time Frame: 7 days prior to the first dose of treatment and pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours post Cycle 1 Day 15 dose ] Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Evidence of histologically or cytologically confirmed diagnosis of locally advanced or 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). ALK+ NSCLC patients must either be treatment naïve in the advanced setting or have had disease progression after 1or 2 previous ALK inhibitor therapy(ies), as the last therapy given. ROS1+ NSCLC patients must either be treatment naïve in the advanced setting or have had disease progression after 1or 2 previous ROS1 inhibitor therapy(ies), as the last therapy given. archival tissue sample available collected prior to enrolment. 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) are eligible. Adequate bone marrow, pancreatic, renal, liver function. Pregnancy test (for females of childbearing potential) negative at screening and at the baseline visit . Male and female patients of childbearing potential must agree to use two highly effective methods of contraception from the time of the first negative pregnancy test at screening, throughout the study and for 90 days after the last dose of assigned treatment. Exclusion Criteria: Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry. Any one of the following currently or in the previous 3 months: myocardial infarction, congenital long QT syndrome, Torsades de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF NY Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism not adequately medically managed with anticoagulants; as well as bradycardia defined as <50 bpms. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥ 2, symptomatic atrial fibrillation of any grade, or QTc interval >=481 msec at screening. Right bundle branch block. History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease. Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, inducers and CYP3A4 substrates with narrow therapeutic indices. Concurrent use of drugs that are CYP2C9 substrates with narrow therapeutic indices or those that are sensitive CYP2B6 substrates.

Contacts/Locations


Central Contact Person:	Pfizer CT.gov Call Center Telephone: 1-800-718-1021
Study Officials:	Pfizer CT.gov Call Center Study Director Pfizer
Locations:

IPDSharing


Plan to Share IPD: