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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00585195




Registration number
NCT00585195
Ethics application status
Date submitted
29/12/2007
Date registered
3/01/2008

Titles & IDs
Public title
A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer
Scientific title
PHASE 1 SAFETY, PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF PF-02341066, A MET/HGFR SELECTIVE TYROSINE KINASE INHIBITOR, ADMINISTERED ORALLY TO PATIENTS WITH ADVANCED CANCER
Secondary ID [1] 0 0
PROFILE 1001
Secondary ID [2] 0 0
A8081001
Universal Trial Number (UTN)
Trial acronym
PROFILE 1001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer ALK-positive 0 0
Non-Small Cell Lung Cancer c-Met Dependent 0 0
Non-Small Cell Lung Cancer ROS Marker Positive 0 0
Systemic Anaplastic Large-Cell Lymphoma 0 0
Advanced Malignancies Except Leukemia 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
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-02341066
Treatment: Drugs - Rifampin
Treatment: Drugs - Itraconazole

Experimental: 1 -


Treatment: Drugs: PF-02341066
Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort).

Treatment: Drugs: Rifampin
600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.

Treatment: Drugs: Itraconazole
Multiple Dose Design: 200 mg QD administered from Cycle 1, Day 1 to Cycle 1, Day 16 (16 days) in combination with PF-02341066.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib
Timepoint [1] 0 0
Cycle 1 (28 days)
Primary outcome [2] 0 0
Dose-Escalation Cohort: Recommended Phase 2 Dose (RP2D) of Crizotinib
Timepoint [2] 0 0
Cycle 1 (28 days)
Primary outcome [3] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Crizotinib on Day -7
Timepoint [3] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7
Primary outcome [4] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Day -7
Timepoint [4] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7
Primary outcome [5] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 1
Timepoint [5] 0 0
Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1
Primary outcome [6] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 15
Timepoint [6] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15
Primary outcome [7] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 2 Day 1
Timepoint [7] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1
Primary outcome [8] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib Cycle 1 Day 15
Timepoint [8] 0 0
Pre-dose on Cycle 1 Day 15
Primary outcome [9] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib on Cycle 2 Day 1
Timepoint [9] 0 0
Pre-dose on Cycle 2 Day 1
Primary outcome [10] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Day -7
Timepoint [10] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7
Primary outcome [11] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 1
Timepoint [11] 0 0
Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1
Primary outcome [12] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 15
Timepoint [12] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15
Primary outcome [13] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 2 Day 1
Timepoint [13] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1
Primary outcome [14] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Day -7
Timepoint [14] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7
Primary outcome [15] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 1
Timepoint [15] 0 0
Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1
Primary outcome [16] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 15
Timepoint [16] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15
Primary outcome [17] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib Cycle 2 Day 1
Timepoint [17] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1
Primary outcome [18] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Plasma Decay Half-Life (t1/2) of Crizotinib on Day -7
Timepoint [18] 0 0
Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7
Primary outcome [19] 0 0
Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)
Timepoint [19] 0 0
up to 189 Months
Primary outcome [20] 0 0
Dose-Escalation Cohort: Number of Participants With Dose-limiting Toxicities (DLT)
Timepoint [20] 0 0
Cycle 1 (28 days)
Primary outcome [21] 0 0
Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib
Timepoint [21] 0 0
pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)
Primary outcome [22] 0 0
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam When Taken Alone or Taken With Crizotinib
Timepoint [22] 0 0
pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)
Primary outcome [23] 0 0
RP2D Cohort: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Crizotinib When Taken With Food
Timepoint [23] 0 0
pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7
Primary outcome [24] 0 0
RP2D Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken With Food
Timepoint [24] 0 0
pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7
Primary outcome [25] 0 0
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib Alone and When Taken With Rifampin
Timepoint [25] 0 0
pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)
Primary outcome [26] 0 0
Rifampin Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib Alone and When Taken With Rifampin
Timepoint [26] 0 0
pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone) and Cycle 2 Day 1 (Crizotinib with Rifampin)
Primary outcome [27] 0 0
Rifampin Cohort: Ctrough of Crizotinib Alone and When Taken With Rifampin
Timepoint [27] 0 0
pre-dose on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)
Primary outcome [28] 0 0
Itraconazole Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib When Taken Alone and When Taken With Itraconazole
Timepoint [28] 0 0
pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)
Primary outcome [29] 0 0
Itraconazole Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib When Taken Alone and When Taken With Itraconazole
Timepoint [29] 0 0
pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)
Primary outcome [30] 0 0
Itraconazole Cohort: Trough Plasma Concentration (Ctrough) of Crizotinib When Taken Alone and When Taken With Itraconazole
Timepoint [30] 0 0
pre-dose on Cycle 1 Day 15 (crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)
Primary outcome [31] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Objective Response (OR)
Timepoint [31] 0 0
Baseline up to 172 months
Primary outcome [32] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Duration of Response (DOR)
Timepoint [32] 0 0
From first documentation of response to date of PD or death due to any cause (up to 172 months)
Primary outcome [33] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Time to Response (TTR)
Timepoint [33] 0 0
From first dose until first documented response of PR or CR (up to 172 months)
Primary outcome [34] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 8
Timepoint [34] 0 0
Week 8
Primary outcome [35] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Percentage of Participants With Disease Control at Week 16
Timepoint [35] 0 0
Week 16
Primary outcome [36] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Progression Free Survival (PFS)
Timepoint [36] 0 0
From randomization until PD or death, whichever occurred first (up to 172 months)
Primary outcome [37] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Probability of Being Event Free at Month 6
Timepoint [37] 0 0
From randomization to 6 months
Primary outcome [38] 0 0
Recommended Phase 2 Dose (RP2D) Cohort: Overall Survival (OS)
Timepoint [38] 0 0
From randomization date to the date of death (up to 172 Months)
Primary outcome [39] 0 0
Probability of Participant Survival at Month 6
Timepoint [39] 0 0
Month 6
Primary outcome [40] 0 0
Probability of Participant Survival at Month 12
Timepoint [40] 0 0
Month 12
Primary outcome [41] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 1 Day 15
Timepoint [41] 0 0
Baseline, Cycle 1 Day 15
Primary outcome [42] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 2 Day 1
Timepoint [42] 0 0
Baseline, Cycle 2 Day 1
Primary outcome [43] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 4 Day 1
Timepoint [43] 0 0
Baseline, Cycle 4 Day 1
Primary outcome [44] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 6 Day 1
Timepoint [44] 0 0
Baseline, Cycle 6 Day 1
Primary outcome [45] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 9 Day 1
Timepoint [45] 0 0
Baseline, Cycle 9 Day 1
Primary outcome [46] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 12 Day 1
Timepoint [46] 0 0
Baseline, Cycle 12 Day 1
Primary outcome [47] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 15 Day 1
Timepoint [47] 0 0
Baseline, Cycle 15 Day 1
Primary outcome [48] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 18 Day 1
Timepoint [48] 0 0
Baseline, Cycle 18 Day 1
Primary outcome [49] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 21 Day 1
Timepoint [49] 0 0
Baseline, Cycle 21 Day 1
Primary outcome [50] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 24 Day 1
Timepoint [50] 0 0
Baseline, Cycle 24 Day 1
Primary outcome [51] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 27 Day 1
Timepoint [51] 0 0
Baseline, Cycle 27 Day 1
Primary outcome [52] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at Cycle 30 Day 1
Timepoint [52] 0 0
Baseline, Cycle 30 Day 1
Primary outcome [53] 0 0
Geometric Mean of Ratio of Total Testosterone, Free Testosterone, Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone, Follicle Stimulating Hormone, Dihydroepiandrosterone Sulfate, Estradiol and Prolactin Levels in Males at End of Treatment
Timepoint [53] 0 0
Baseline, End of Treatment (28 days post last dose)

Eligibility
Key inclusion criteria
* Advanced malignancies (except leukemias), histologically proven at diagnosis; Histologically confirmed advanced malignancies that are known to be sensitive to PF-03241066 inhibition, e.g. ALK, c-MET and ROS
* Solid tumors must have measurable disease (Recommended Phase 2 Dose Cohort patients with non-measurable disease may enter on a case-by-case basis); not required for DDI sub-studies.
* Adequate blood cell counts, kidney function, liver function and Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (for the Recommended Phase 2 Cohort, a ECOG score of 2 may be allowed on a case-by-case basis)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Major surgery, radiation therapy or anti-cancer therapy within 2 to 4 weeks of starting study treatment, depending on the patient cohort
* Prior stem cell transplant except of patients with neuroblastoma, lymphoma or myeloma
* Active or unstable cardiac disease or heart attack within 3 months of starting study treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Parallel
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
19/04/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/01/2022
Sample size
Target
Accrual to date
Final
596
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Vermont
Country [12] 0 0
Japan
State/province [12] 0 0
Aichi
Country [13] 0 0
Japan
State/province [13] 0 0
Hyogo
Country [14] 0 0
Japan
State/province [14] 0 0
Osaka
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul

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)?
No
No/undecided IPD sharing reason/comment
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.


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/NCT00585195