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Trial record 6 of 11 for:    PF-03084014

A Study Evaluating The PF-03084014 In Combination With Docetaxel In Patients With Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT01876251
Recruitment Status : Terminated (The study was terminated on June 24th, 2015 due to change in strategy of PF-03084014 development. There were no safety/efficacy concerns behind the decision.)
First Posted : June 12, 2013
Results First Posted : March 15, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This study is aimed to determine the tolerability of the PF-03084014 plus docetaxel combination in patients with advanced breast cancer. Preliminary information about the efficacy of the combination will also be collected.

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Drug: PF-03084014 Drug: Docetaxel Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Study Of Docetaxel + Pf 03084014 In Metastatic Or Locally Recurrent/Advanced Triple Negative Breast Cancer
Actual Study Start Date : November 4, 2013
Actual Primary Completion Date : December 24, 2015
Actual Study Completion Date : December 24, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: PF-03084014 plus docetaxel
PF 03084014 will be administered orally, continuously, twice daily at doses from 80 to 150 mg in combination with docetaxel given every 3 weeks at doses from 75 to 100 mg/m^2
Drug: PF-03084014
Tablet, 10 mg, twice a day

Drug: PF-03084014
Tablet, 50 mg, twice a day

Drug: PF-03084014
Tablet, 100 mg, twice a day

Drug: Docetaxel
Solution for IV infusion 75 mg/m^2, every 3 weeks
Other Name: Taxotere

Drug: Docetaxel
Solution for IV infusion 100 mg/m^2, every 3 weeks




Primary Outcome Measures :
  1. Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1 [ Time Frame: Cycle 1 Days 1-21 ]
    Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia (Grade more than or equal to [>=] 3 and body temperature >=38.5 degrees Celsius); Grade >=3 neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade >=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities.

  2. Progression-free Survival (PFS) at 6 Months - Expansion Cohort [ Time Frame: Baseline till 6 months post-dose ]
    The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.


Secondary Outcome Measures :
  1. Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs [ Time Frame: Baseline up to 28-35 days after treatment discontinuation (up to Day 280) ]
    An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs (TEAEs) are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Causality assessment was made by the investigator. Grading was per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death related to AE.

  2. Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 28-35 days after treatment discontinuation (up to Day 280) ]
    Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick).

  3. Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline, every 6 weeks from Cycle 2 onwards up to 26 months ]
    OR was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 millimeters [mm]). No new lesions. PR was defined as more than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

  4. Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort [ Time Frame: Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12) ]
    Serum PF-03084014 pharmacokinetic (PK) parameters were calculated following twice daily (BID) doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1).

  5. AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

  6. Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1)

  7. Cmax of Docetaxel in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

  8. Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1)

  9. Tmax of Docetaxel in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

  10. Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

  11. Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

  12. Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort [ Time Frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12) ]
    Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

  13. AUClast of PF-03084014 in the Expansion Cohort [ Time Frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) ]
  14. Cmax of PF-03084014 in the Expansion Cohort [ Time Frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) ]
  15. Tmax of PF-03084014 in the Expansion Cohort [ Time Frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) ]
  16. Ctrough of PF-03084014 in the Expansion Cohort [ Time Frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12) ]
  17. Duration of Response (DR) [ Time Frame: Baseline up to 28-35 days after treatment discontinuation (up to Day 280) ]
    Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

  18. Number of Participants With QTc Values Meeting Categorical Summarization Criteria [ Time Frame: Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12) ]
    Criteria for categorical summarization of the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT) corrected for heart rate (QTc) using Bazett's correction (QTcB) or Fridericia's correction (QTcF) included: maximum QTcB or QTcF less than or equal to (<=) 450 milliseconds (msec), 450 to <=480 msec, 480 to <=500 msec, more than (>) 500 msec; maximum QTcB or QTcF changes (increases/decreases) from baseline (BL) less than (<) 30 msec, 30 to <60 msec, more than or equal to (>=) 60 msec.

  19. Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood [ Time Frame: C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12) ]
    As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of breast cancer with evidence of a) metastatic or b) locally recurrent/advanced disease.

Exclusion Criteria:

  • Prior treatment with a gamma secretase inhibitors or other Notch signaling inhibitors.

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): NCT01876251


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham, IDS Pharmacy
Birmingham, Alabama, United States, 35249
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, California
Stanford Cancer Institute
Stanford, California, United States, 94305
Stanford Hospital & Clinics-DRUG SHIPMENT ADDRESS only
Stanford, California, United States, 94305
Stanford Hospital & Clinics
Stanford, California, United States, 94305
Stanford Women's Cancer Center
Stanford, California, United States, 94305
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Karmanos Cancer Institute (KCI)
Detroit, Michigan, United States, 48201
United States, North Carolina
UNC Cancer Hospital Infusion Pharmacy
Chapel Hill, North Carolina, United States, 27514
UNC Hospitals, The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7600
Belgium
Jules Bordet Institut
Bruxelles, Belgium, 1000
Grand Hopital de Charleroi
Charleroi, Belgium, 6000
Italy
Instituto Europeo di Oncologia
Milano, Italy, 20141
Spain
Instituto Catalan de Oncologia de L'Hospitalet de Llobregat(ICO)
Barcelona, Spain, 08908
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01876251    
Other Study ID Numbers: A8641016
2013-000659-41 ( EudraCT Number )
First Posted: June 12, 2013    Key Record Dates
Results First Posted: March 15, 2019
Last Update Posted: March 15, 2019
Last Verified: March 2019
Keywords provided by Pfizer:
Breast cancer metastatic
docetaxel
PF-03084014
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action