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Triple Negative Breast NeoplasmsPhase 2NCT02299635

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

A Phase 2 study testing PF-03084014 in people with Triple Negative Breast Neoplasms, run by Pfizer at 37 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple Negative Breast Neoplasms
What is being tested?
PF-03084014
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
37 sitesin 6 countries
Study dates
3 Feb 2015to 14 Jan 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Known brain metastases.
  • Prior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.

Trial locations and contacts

37 sites in 6 countries.

37 sites in 6 countries

United States18 sites

  • Memorial Sloan Kettering Cancer Center Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Brigham and Women's Hospital (BWH)

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute (DFCI)

    Boston, Massachusetts, 02215

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Memorial Sloan Kettering Cancer Center Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Cancer Center West Harrison

    Harrison, New York, 10604

  • University of Chicago Comprehensive Cancer Center at Silver Cross Hospital

    New Lenox, Illinois, 60451

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • The Valley Hospital - Luckow Pavilion

    Paramus, New Jersey, 07652

  • Valley Medical Group

    Paramus, New Jersey, 07652

  • Memorial Sloan Kettering Cancer Center Rockville Centre

    Rockville Centre, New York, 11570

  • Memorial Sloan Kettering Cancer Center Sleepy Hollow

    Sleepy Hollow, New York, 10591

  • Stanford Cancer Institute

    Stanford, California, 94305

  • Stanford Hospital and Clinics

    Stanford, California, 94305

  • Stanford Women's Cancer Center

    Stanford, California, 94305

  • Valley Medical Group

    Westwood, New Jersey, 07675

  • Midwestern Regional Medical Center

    Zion, Illinois, 60099

Other trials in United States

Spain9 sites

  • Complejo Hospitalario Universitario A Coruna (Hospital Teresa Herrera)

    A Coruña, 15006

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Instituto Catalan de Oncologia de L'Hospitalet de Llobregat (ICO)

    Barcelona, 08908

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow, Scotland, G12 0YN

  • Ross Hall Hospital

    Glasgow, Scotland, G52 3NQ

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • The Royal Marsden NHS Foundation Trust

    Surrey, SM2 5PT

Other trials in United Kingdom

Poland3 sites

  • Vesalius

    Krakow, 31108

  • Vesalius Poradnia Onkologiczna i Hematologiczna

    Krakow, 31216

  • Szpital Kliniczny Przemienienia Panskiego, Uniwersutetu Medycznego im. Karola Marcinkowskiego

    Poznan, 60-569

Other trials in Poland

Italy2 sites

  • Presidio Ospedaliero Vito Fazzi

    Lecce, 73100

  • Istitutio Europeo di Oncologia

    Milan, 20141

Other trials in Italy

Hungary1 site

  • Debreceni Egyetem, Klinikai Kozpont, Onkologiai Intezet

    Debrecen, 4032

Other trials in Hungary

About this study

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

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-)

Being tested
PF-03084014
Keywords
PF-03084014, Notch Alterations
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-03084014Drug

    Tablet, 10 mg, twice a day.

  • PF-03084014Drug

    Tablet, 50 mg, twice a day

  • PF-03084014Drug

    Tablet, 100 mg, twice a day

Study groups in NCT02299635
Study groupRoleWhat they receive
PF-03084014ExperimentalPF-03084014 will be administered orally, continuously, twice daily at 150 mg, but the dose can be reduced to 100 mg or 80 mg.
Receives: Drug: PF-03084014

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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 (15)

  1. 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.

    Measured: 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.

  2. 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.

    Measured: 2 years

  3. 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.

    Measured: 2 years

  4. 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.

    Measured: 1 year

  5. 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.

    Measured: 2 years

  6. Type of Notch Genomic Alterations in Participants With NA+ mTNBC

    Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC

    Measured: 2 years

  7. Pre-dose Serum Concentration (Ctrough) for PF-03084014

    Measured: Day 1 of Cycle 1, 2, 3, and 5

  8. 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.

    Measured: Day 1 of Cycle 1, 2, 3, and 5

  9. 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.

    Measured: Day 1 of Cycle 1, 2, 3, and 5

  10. 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.

    Measured: 2 years

  11. 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.

    Measured: 2 years

  12. Number of Participants With Laboratory Test (Hematology) Abnormalities

    Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.

    Measured: Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.

  13. Number of Participants With Laboratory Test (Chemistry) Abnormalities

    Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities

    Measured: 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

  14. 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.

    Measured: Day 1 of Cycle 1

  15. Number of Notch Genomic Alterations in Participants With NA+ mTNBC

    Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2014 (estimated)
  2. Study start3 Feb 2015
  3. Primary completion14 Jan 2016
  4. Study completion14 Jan 2016

Why it stopped: 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.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02299635
Sponsor's protocol ID
A8641020
Other IDs
2014-002286-30, 2014
Status last verified
Dec 2018
First submitted
20 Nov 2014
Last updated
8 Jan 2019
Data monitoring committee
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PF-03084014 in people with Triple Negative Breast Neoplasms, run by Pfizer at 37 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Spain, United Kingdom, Poland, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02299635.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.

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