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A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations

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ClinicalTrials.gov Identifier: NCT02299635
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 : November 24, 2014
Results First Posted : January 13, 2017
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 20, 2014
First Posted Date  ICMJE November 24, 2014
Results First Submitted Date  ICMJE November 17, 2016
Results First Posted Date  ICMJE January 13, 2017
Last Update Posted Date January 8, 2019
Actual Study Start Date  ICMJE February 3, 2015
Actual Primary Completion Date January 14, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2016)
Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+) [ Time Frame: Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first. ]
OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis less than [<]10 millimeter [mm]). PR: Greater than or equal to (>=)30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2014)
Objective response (OR) in Patients With NA+ mTNBC [ Time Frame: > 6 months ]
OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Change History Complete list of historical versions of study NCT02299635 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2016)
  • OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-) [ Time Frame: Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first. ]
    OR status based on assessment of confirmed CR or confirmed PR according to RECIST 1.1. CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis <10 mm). PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.
  • Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC [ Time Frame: 2 years ]
    The period from study entry until disease progression, death, whichever occurred first as per RECIST version 1.1.
  • Duration of Response (DR) in Participants With NA+ or NA mTNBC [ Time Frame: 2 years ]
    Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated for the subgroup of patients with a confirmed objective tumor response. Objective Progression (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.
  • One-Year Survival Probability in Participants With NA+ or NA mTNBC [ Time Frame: 1 year ]
    Overall survival (OS) status (alive or not) at 1 year after study entry. The the survival probability at 1 year was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.
  • Overall Survival (OS) in Participants With NA+ or NA mTNBC [ Time Frame: 2 years ]
    OS was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
  • Type of Notch Genomic Alterations in Participants With NA+ mTNBC [ Time Frame: 2 years ]
    Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
  • Pre-dose Serum Concentration (Ctrough) for PF-03084014 [ Time Frame: Day 1 of Cycle 1, 2, 3, and 5 ]
  • Pharmacodynamic (PD) Effects of PF‑03084014 in Tumor Specimens and Peripheral Blood [ Time Frame: Day 1 of Cycle 1, 2, 3, and 5 ]
    Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.
  • Alterations in Genes, Proteins, and RNAs Relevant to the Notch Signaling Pathway, to TNBC Biology, and to Sensitivity/Resistance to PF-03084014 in Tumor Specimens and Peripheral Blood. [ Time Frame: Day 1 of Cycle 1, 2, 3, and 5 ]
    Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: 2 years ]
    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. 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. Treatment-emergent AEs were defined as all deaths, regardless of cause, from treatment start until 28 days after the last dose and non-fatal events occurring after treatment start regardless of cause, up until 28 days after the last dose or until start of new anti-cancer treatment, whichever was first.
  • Number of Participants With Treatment-Emergent AEs by CTCAE Grade [ Time Frame: 2 years ]
    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
  • Number of Participants With Laboratory Test (Hematology) Abnormalities [ Time Frame: Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles. ]
    Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.
  • Number of Participants With Laboratory Test (Chemistry) Abnormalities [ Time Frame: Day 1 and Day 15 of Cycles 1, 2, 3, 4, 5, and subsequent cycles up to Cycle 8 and Day 8 of Cycle 1 ]
    Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities
  • Number of Participants With Laboratory Test (Urinalysis) Abnormalities [ Time Frame: Day 1 of Cycle 1 ]
    Number of participants with CTCAE version 4.03 grade 1 to 4 urinalysis test abnormalities for urine protein.
  • Number of Notch Genomic Alterations in Participants With NA+ mTNBC [ Time Frame: 2 years ]
    Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2014)
  • OR in Patients With NA- mTNBC [ Time Frame: > 6 months ]
    OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Progression-Free Survival (PFS) [ Time Frame: 2 years ]
    The period from study entry until disease progression, death, whichever occurs first.
  • Duration of Response (DR) [ Time Frame: 2 years ]
    Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated for the subgroup of patients with a confirmed objective tumor response.
  • One-year survival probability [ Time Frame: 1 year ]
    OS status (alive or not) at 1 year after study entry. The 1-year OS probability is summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.
  • Overall Survival (OS) [ Time Frame: 2 years ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
  • Type and number of Notch genomic alterations identified by NGS assay in patients with NA+ mTNBC [ Time Frame: 2 years ]
    Type and number of Notch genomic alterations identified by NGS assay in patients with NA+ mTNBC
  • PF-03084014 serum Ctrough levels [ Time Frame: 2 years ]
    PF-03084014 serum Ctrough levels
  • Pharmacodynamic effects of PF 03084014 in tumor specimens and peripheral blood [ Time Frame: 2 years ]
    Change in analyte expression.
  • Alterations in genes, proteins, and RNAs relevant to the Notch signaling pathway, to TNBC biology, and to sensitivity/resistance to PF 03084014 in tumor specimens and peripheral blood [ Time Frame: 2 years ]
    Changes in RNA or protein levels.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations
Official Title  ICMJE PHASE 2 STUDY OF SINGLE-AGENT PF-03084014 IN PATIENTS WITH ADVANCED TRIPLE-NEGATIVE BREAST CANCER WITH OR WITHOUT GENOMIC ALTERATIONS IN NOTCH RECEPTORS
Brief Summary This study is designed to evaluate the preliminary anti-tumor activity and tolerability of PF-03084014 when administered as a single agent in the treatment of patients with advanced triple receptor-negative breast cancer (mTNBC) harboring genomic alterations in Notch receptors (NA+), and in a smaller subset of mTNBC patients whose tumor tests negative for genomic alterations in Notch receptors (NA-)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Neoplasms
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: PF-03084014
PF-03084014 will be administered orally, continuously, twice daily at 150 mg, but the dose can be reduced to 100 mg or 80 mg.
Interventions:
  • Drug: PF-03084014
  • Drug: PF-03084014
  • Drug: PF-03084014
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: January 26, 2016)
19
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2014)
48
Actual Study Completion Date  ICMJE January 14, 2016
Actual Primary Completion Date January 14, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological or cytological diagnosis of triple negative breast cancer (TNBC) with evidence of a) metastatic or b) locally recurrent advanced disease that is not amenable to resection or radiotherapy with curative intent.
  • Availability of an original diagnostic tumor tissue or the most recent metastatic tumor biopsies (archival biopsy or de novo biopsy) and a peripheral blood sample for Notch receptors genomic profiling

Exclusion Criteria:

  • Known brain metastases.
  • Prior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
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 Hungary,   Italy,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries France,   Germany
 
Administrative Information
NCT Number  ICMJE NCT02299635
Other Study ID Numbers  ICMJE A8641020
2014-002286-30 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
URL: 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 December 2018

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