Clinical trial NCT02299635: A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations
Official title: PHASE 2 STUDY OF SINGLE-AGENT PF-03084014 IN PATIENTS WITH ADVANCED TRIPLE-NEGATIVE BREAST CANCER WITH OR WITHOUT GENOMIC ALTERATIONS IN NOTCH RECEPTORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Triple Negative Breast Neoplasms
Keywords: PF-03084014
Notch Alterations
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-11-24
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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-)


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+)
timeFrame: 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.
Secondary outcomes:
measure: OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-)
timeFrame: 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.
measure: Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC
timeFrame: 2 years
measure: Duration of Response (DR) in Participants With NA+ or NA mTNBC
timeFrame: 2 years
measure: One-Year Survival Probability in Participants With NA+ or NA mTNBC
timeFrame: 1 year
measure: Overall Survival (OS) in Participants With NA+ or NA mTNBC
timeFrame: 2 years
measure: Type of Notch Genomic Alterations in Participants With NA+ mTNBC
timeFrame: 2 years
measure: Pre-dose Serum Concentration (Ctrough) for PF-03084014
timeFrame: Day 1 of Cycle 1, 2, 3, and 5
measure: Pharmacodynamic (PD) Effects of PF-03084014 in Tumor Specimens and Peripheral Blood
timeFrame: Day 1 of Cycle 1, 2, 3, and 5
measure: 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.
timeFrame: Day 1 of Cycle 1, 2, 3, and 5
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: 2 years
measure: Number of Participants With Treatment-Emergent AEs by CTCAE Grade
timeFrame: 2 years
measure: Number of Participants With Laboratory Test (Hematology) Abnormalities
timeFrame: Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.
measure: Number of Participants With Laboratory Test (Chemistry) Abnormalities
timeFrame: 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
measure: Number of Participants With Laboratory Test (Urinalysis) Abnormalities
timeFrame: Day 1 of Cycle 1
measure: Number of Notch Genomic Alterations in Participants With NA+ mTNBC
timeFrame: 2 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Stanford
country: United States
facility: Stanford Women's Cancer Center
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital (BWH)
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (DFCI)
state: Massachusetts
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center Basking Ridge
state: New Jersey
city: Paramus
country: United States
facility: The Valley Hospital - Luckow Pavilion
state: New Jersey
city: Paramus
country: United States
facility: Valley Medical Group
state: New Jersey
city: Westwood
country: United States
facility: Valley Medical Group
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center West Harrison
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Cancer Center Rockville Centre
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Cancer Center Sleepy Hollow
state: New York
city: Debrecen
country: Hungary
facility: Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet
city: Lecce
country: Italy
facility: Presidio Ospedaliero Vito Fazzi
city: Milan
country: Italy
facility: Istitutio Europeo di Oncologia
city: Krakow
country: Poland
facility: Vesalius
city: Krakow
country: Poland
facility: Vesalius Poradnia Onkologiczna i Hematologiczna
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Glasgow
country: United Kingdom
facility: Ross Hall Hospital
state: Scotland
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: