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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)

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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

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.

Condition or disease Intervention/treatment Phase
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 Drug: PF-02341066 Drug: Rifampin Drug: Itraconazole Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 596 participants
Allocation: N/A
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : April 19, 2006
Actual Primary Completion Date : July 30, 2020
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Crizotinib

Arm Intervention/treatment
Experimental: 1 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.




Primary Outcome Measures :
  1. 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.

  2. Maximum tolerated dose (MTD) [ Time Frame: Baseline up to 28 days (1 cycle) after the start of each increased treatment dose ]
  3. Incidence of participants with Dose Limiting Toxicities (DLTs) in Cycle 1 [ Time Frame: Baseline up to 28 days (1 cycle) ]
  4. Determine Recommended Phase 2 Dose (RP2D) [ Time Frame: Baseline up to 28 days (1 cycle) ]
  5. 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).

  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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.

  10. 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.

  11. 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.

  12. 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).

  13. 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)

  14. 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 ]
  15. 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.

  16. 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 ]
  17. 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 ]
  18. Maximum Observed Plasma Concentration (Cmax) of PF-02341066 with and without rifampin [ Time Frame: 0, 2, 4, 6, 8, and 10 hours post-dose ]
  19. 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 ]
  20. 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 ]
  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. 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

  28. 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

  29. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00585195


Locations
Show Show 29 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00585195    
Other Study ID Numbers: A8081001
PROFILE 1001 ( Other Identifier: Alias Study Number )
First Posted: January 3, 2008    Key Record Dates
Last Update Posted: March 15, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
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.
Keywords provided by Pfizer:
Crizotinib
dose-finding
drug-drug interaction
ALK rearrangements
c-Met mutations or amplifications
c-Met dependent tumors
ROS1 rearrangements
c-Met exon 14 deletion
c-Met exon 14 skipping
c-Met exon 14 alterations
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Lymphoma, Large-Cell, Anaplastic
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Itraconazole
Rifampin
Crizotinib
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists