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

Triple Negative Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02299635
• Other study ID #: A8641020
• Secondary ID: 2014-002286-30
• Status: Terminated
• Phase: Phase 2
• Start date: February 3, 2015
• Est. completion date: January 14, 2016

Study information

• Verified date: December 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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-)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: January 14, 2016
• Est. primary completion date: January 14, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• PF-03084014
Tablet, 10 mg, twice a day.
• PF-03084014
Tablet, 50 mg, twice a day
• PF-03084014
Tablet, 100 mg, twice a day

Locations

Country	Name	City	State
Hungary	Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet	Debrecen
Italy	Presidio Ospedaliero Vito Fazzi	Lecce
Italy	Istitutio Europeo di Oncologia	Milan
Poland	Vesalius	Krakow
Poland	Vesalius Poradnia Onkologiczna i Hematologiczna	Krakow
Poland	Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego	Poznan
Spain	Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)	A Coruna
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Ross Hall Hospital	Glasgow	Scotland
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	The Royal Marsden NHS Foundation Trust	Surrey
United States	Memorial Sloan Kettering Cancer Center Basking Ridge	Basking Ridge	New Jersey
United States	Brigham and Women's Hospital (BWH)	Boston	Massachusetts
United States	Dana-Farber Cancer Institute (DFCI)	Boston	Massachusetts
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Memorial Sloan Kettering Cancer Center Commack	Commack	New York
United States	Memorial Sloan Kettering Cancer Center West Harrison	Harrison	New York
United States	University of Chicago Comprehensive Cancer Center at Silver Cross Hospital	New Lenox	Illinois
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
United States	Valley Medical Group	Paramus	New Jersey
United States	Memorial Sloan Kettering Cancer Center Rockville Centre	Rockville Centre	New York
United States	Memorial Sloan Kettering Cancer Center Sleepy Hollow	Sleepy Hollow	New York
United States	Stanford Cancer Institute	Stanford	California
United States	Stanford Hospital and Clinics	Stanford	California
United States	Stanford Women's Cancer Center	Stanford	California
United States	Valley Medical Group	Westwood	New Jersey
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Hungary,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response (OR) Rate in Participants With Advanced Triple Receptor-Negative Breast Cancer (mTNBC) Harboring Activating Genomic Alterations in Notch Receptors (NA+)	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.	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	OR Rate in Participants With mTNBC Whose Tumors Tested Negative for Eenomic Alterations in Notch Receptor (NA-)	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.	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	Progression-Free Survival (PFS) in Participants With NA+ or NA mTNBC	The period from study entry until disease progression, death, whichever occurred first as per RECIST version 1.1.	2 years
Secondary	Duration of Response (DR) in Participants With NA+ or NA mTNBC	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.	2 years
Secondary	One-Year Survival Probability in Participants With NA+ or NA mTNBC	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.	1 year
Secondary	Overall Survival (OS) in Participants With NA+ or NA mTNBC	OS was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.	2 years
Secondary	Type of Notch Genomic Alterations in Participants With NA+ mTNBC	Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC	2 years
Secondary	Pre-dose Serum Concentration (Ctrough) for PF-03084014		Day 1 of Cycle 1, 2, 3, and 5
Secondary	Pharmacodynamic (PD) Effects of PF-03084014 in Tumor Specimens and Peripheral Blood	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.	Day 1 of Cycle 1, 2, 3, and 5
Secondary	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.	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.	Day 1 of Cycle 1, 2, 3, and 5
Secondary	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	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.	2 years
Secondary	Number of Participants With Treatment-Emergent AEs by CTCAE Grade	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.	2 years
Secondary	Number of Participants With Laboratory Test (Hematology) Abnormalities	Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.	Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.
Secondary	Number of Participants With Laboratory Test (Chemistry) Abnormalities	Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities	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
Secondary	Number of Participants With Laboratory Test (Urinalysis) Abnormalities	Number of participants with CTCAE version 4.03 grade 1 to 4 urinalysis test abnormalities for urine protein.	Day 1 of Cycle 1
Secondary	Number of Notch Genomic Alterations in Participants With NA+ mTNBC	Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC	2 years

External Links

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