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A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer (PROFILE 1001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00585195
Recruitment Status : Active, not recruiting
First Posted : January 3, 2008
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE December 29, 2007
First Posted Date  ICMJE January 3, 2008
Last Update Posted Date March 15, 2021
Actual Study Start Date  ICMJE April 19, 2006
Actual Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2021)
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: baseline through approximately 10 years ]
    Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
  • Maximum tolerated dose (MTD) [ Time Frame: Baseline up to 28 days (1 cycle) after the start of each increased treatment dose ]
  • Incidence of participants with Dose Limiting Toxicities (DLTs) in Cycle 1 [ Time Frame: Baseline up to 28 days (1 cycle) ]
  • Determine Recommended Phase 2 Dose (RP2D) [ Time Frame: Baseline up to 28 days (1 cycle) ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9, 24 and 48 hours post-dose, and at any two of the following: 72, 96, 120 or 144 hours post-dose ]
    AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9, 24 and 48 hours post-dose, and at any two of the following: 72, 96, 120 or 144 hours post-dose ]
  • Maximum Observed Plasma Concentration (Cmax) of PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9, 24 and 48 hours post-dose, and at any two of the following: 72, 96, 120 or 144 hours post-dose ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9, 24 and 48 hours post-dose, and at any two of the following: 72, 96, 120 or 144 hours post-dose ]
  • Plasma Decay Half-Life (t1/2) of PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9, 24 and 48 hours post-dose, and at any two of the following: 72, 96, 120 or 144 hours post-dose ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Apparent Oral Clearance (CL/F) of PF-02341066 [ Time Frame: Week 2 and 4 ]
    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.
  • Percent Cumulative Amount of Drug Recovered Unchanged in Urine (Ae) [ Time Frame: 0 to 4 hours, 4-12 hours and 12-24 hour post-dose ]
    Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Cumulative amount was calculated as sum of urine drug concentration in sample volume for each collection interval. Sample volume = (urine weight in gram [g]/1.020), where 1.020 g/mL is the approximate specific gravity of urine.
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Midazolam with and without PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9 and 24 hours post-dose ]
    AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Midazolam with and without PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9 and 24 hours post-dose ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • Maximum Observed Plasma Concentration (Cmax) of Midazolam with and without PF-02341066 [ Time Frame: 0, 1, 2, 4, 6, 8, 9 and 24 hours post-dose ]
  • Area Under the Curve From Time Zero to 24 hours (AUC24) of PF-02341066 with and without food [ Time Frame: 0, 1, 2, 4, 6, 8, 9, 24 and 48 hours post-dose ]
    AUC24 is a measure of the serum concentration of the drug over 24 hours. It is used to characterize drug absorption.
  • Maximum Observed Plasma Concentration (Cmax) of PF-02341066 with and without food [ Time Frame: 0, 1, 2, 4, 6, 8, 24 and 48 hours post-dose ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-02341066 with and without rifampin [ Time Frame: 0, 2, 4, 6, 8, and 10 hours post-dose ]
  • Maximum Observed Plasma Concentration (Cmax) of PF-02341066 with and without rifampin [ Time Frame: 0, 2, 4, 6, 8, and 10 hours post-dose ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-02341066 with and without itraconazole [ Time Frame: 0, 1, 2, 4, 6, 8, 9 and 24 hours post-dose ]
  • Maximum Observed Plasma Concentration (Cmax) of PF-02341066 with and without itraconazole [ Time Frame: 0, 1, 2, 4, 6, 8, 9 and 24 hours post-dose ]
  • Objective Response Rate - Percentage of Participants With Objective Response [ Time Frame: Baseline up to 24 months ]
    Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
  • Duration of response [ Time Frame: Baseline up to 24 months ]
    Defined as the time (in months) from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed, to the first documentation of objective tumor progression or death on study due to any cause, whichever occurs first.
  • Time to response (TTR) [ Time Frame: Every 8 weeks from the date of first dose up to 2 years ]
    TTR is defined as the time from date of first dose to first documentation of objective tumor response (CR or PR). For participants whose objective response (OR) proceeds from PR to CR, the onset of PR is taken as the onset of response. TTR will only be calculated for the subgroup of participants with a confirmed objective tumor response.
  • Disease Control Rate (DCR) [ Time Frame: Every 8 weeks from date of first dose up to 2 years ]
    DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST 1.0 or RECIST 1.1, at Weeks 8 and 16.
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to 24 months ]
    Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
  • Overall Survival (OS) Rate [ Time Frame: Date of first dose of study drug up to 24 months ]
    OS was based on Kaplan-Meier method. Survival was defined as the time period from the date of first dose to the date of death, censored at the participant's last contact date. Percent of participants with OS were estimated.
  • Probability of Participant Survival at 6 and 12 months [ Time Frame: Baseline up to 6 and 12 months ]
    Probability of survival at 6 or 12 months after first dose of study treatment
  • Probability of progression-fres survival (PFS) at 6 months [ Time Frame: Baseline up to 6 months ]
    Probability of being alive and progression-free at 6 months after the date of first dose based on the Kaplan-Meier estimate
  • Level of total testosterone, free testosterone, sex hormone binding globulin (SHBG), luteinizing hormone, follicle stimulating hormone, dihydroepiandosterone sulfate, estradiol, and prolactin in males. [ Time Frame: Baseline up to 4 months ]
    Geometric means of the postbaseline/baseline ratio were summarized for total testosterone, free testosterone, sex hormone binding globulin (SHBG), luteinizing hormone, follicle stimulating hormone, dihydroepiandosterone sulfate, estradiol, and prolactin.
Original Primary Outcome Measures  ICMJE
 (submitted: December 29, 2007)
  • To find the dose of PF-02341066 that should be used in future clinical trials [ Time Frame: 2.5 years ]
  • To test the safety of PF-02341066 when taken by people who have cancer [ Time Frame: 2.5 years ]
  • To assess how the body handles blood concentrations of PF-02341066 [ Time Frame: 2.0 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer
Official Title  ICMJE PHASE 1 SAFETY, PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF PF-02341066, A MET/HGFR SELECTIVE TYROSINE KINASE INHIBITOR, ADMINISTERED ORALLY TO PATIENTS WITH ADVANCED CANCER
Brief Summary PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Small Cell Lung Cancer ALK-positive
  • Non-Small Cell Lung Cancer c-Met Dependent
  • Non-Small Cell Lung Cancer ROS Marker Positive
  • Systemic Anaplastic Large-Cell Lymphoma
  • Advanced Malignancies Except Leukemia
Intervention  ICMJE
  • Drug: 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).
  • Drug: Rifampin
    600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.
  • Drug: 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.
Study Arms  ICMJE Experimental: 1
Interventions:
  • Drug: PF-02341066
  • Drug: Rifampin
  • Drug: Itraconazole
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 7, 2020)
596
Original Estimated Enrollment  ICMJE
 (submitted: December 29, 2007)
60
Estimated Study Completion Date  ICMJE December 31, 2022
Actual Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Japan,   Korea, Republic of,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00585195
Other Study ID Numbers  ICMJE A8081001
PROFILE 1001 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: 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.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP