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A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study) (ABRAZO)

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ClinicalTrials.gov Identifier: NCT02034916
Recruitment Status : Terminated (Primary Analysis and study completed. Not stopped due to safety concerns.)
First Posted : January 14, 2014
Results First Posted : November 6, 2017
Last Update Posted : July 31, 2019
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

Brief Summary:

The purpose of this 2-stage, 2-cohort Phase 2 trial is to evaluate the safety and efficacy of talazoparib (also known as BMN 673) in subjects with locally advanced or metastatic breast cancer with a deleterious germline BRCA 1 or BRCA 2 mutation. Subjects will be assigned to either Cohort 1 or 2 based on prior chemotherapy for metastatic disease:

  • Cohort 1) Subjects with a documented PR or CR to a prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum; or
  • Cohort 2) Subjects who have received > 2 prior chemotherapy regimens for metastatic disease and who have had no prior platinum therapy for metastatic disease

Condition or disease Intervention/treatment Phase
Breast Neoplasms BRCA 1 Gene Mutation BRCA 2 Gene Mutation Drug: talazoparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 2, 2-STAGE, 2-COHORT STUDY OF TALAZOPARIB (BMN 673) ADMINISTERED TO GERMLINE BRCA MUTATION SUBJECTS WITH LOCALLY ADVANCED AND/OR METASTATIC BREAST CANCER
Actual Study Start Date : December 13, 2013
Actual Primary Completion Date : September 1, 2016
Actual Study Completion Date : October 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: talazoparib

Cohort 1) Subjects with a documented PR or CR to a prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum

Cohort 2) Subjects who have received > 2 prior chemotherapy regimens for metastatic disease and who have had no prior platinum therapy for metastatic disease

Drug: talazoparib
Other Names:
  • MDV3800
  • BMN673




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: From randomization until data cutoff date (01 Sep 2016) ]
    ORR: Percentage of participants with a confirmed best overall complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1). CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than (<) 10 millimeter (mm) in short axis. PR: Greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions, compared to the sum at baseline. Response evaluation was done by an independent radiology facility (IRF).


Secondary Outcome Measures :
  1. Clinical Benefit Rate-24 (CBR-24) [ Time Frame: From randomization until data cutoff date (01 Sep 2016) ]
    CBR24: Percentage of participants with a best response of CR, PR or stable disease (SD) sustained for at least 24 weeks, as assessed by IRF using RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.

  2. Duration of Response (DOR) [ Time Frame: From first documentation of CR or PR until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016]) ]
    DOR: Time from first documentation of CR or PR, to PD by IRF assessment using RECIST 1.1, or to death due to any cause, whichever occurred first. CR: Disappearance of all non-nodal target and non-target lesions, with target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PD or death at the analysis date were censored at last tumor assessment date prior to on or before initiation of a new anticancer therapy or before the data cutoff date.

  3. Progression Free Survival (PFS) [ Time Frame: From first dose of study drug until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016]) ]
    PFS was defined as the time in months from the first dose of study drug to the first documentation of PD by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PFS event at the analysis were censored at last tumor assessment date prior to data cutoff or date of new anticancer treatment initiation, whichever occurred first.

  4. Overall Survival (OS) [ Time Frame: From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016]) ]
    OS was defined as the time from first dose of study drug to death due to any cause. For participants without a death date at the time of data cutoff or permanently lost to follow-up, OS was right-censored at the date the participant was last known to be alive on or before the data cutoff date.

  5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016]) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria . A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.

  6. Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016]) ]
    A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A treatment-related SAE was a treatment-related 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; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria.

  7. Number of Participants With Outcome in Response to Adverse Events (AEs) [ Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016]) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: 'Is the AE leading to study discontinuation or death?' as 'yes'.

  8. Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameters [ Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016]) ]
    Laboratory tests included hematology (hemoglobin [low], leucocytes [low], lymphocytes [low], neutrophils [low], platelets [low]) and serum chemistry (alanine aminotransferase [high], albumin [low], alkaline phosphatase [high], aspartate aminotransferase [high], bilirubin [high], calcium [low], glucose [high], magnesium [low], phosphate [low], potassium [high], potassium [low], sodium [high], sodium [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for hematology and chemistry laboratory parameters is reported in this outcome measure.

  9. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016]) ]
    Criteria for clinically significant vital sign changes: 1) Blood pressure: systolic blood pressure (SBP): >=30 millimeters of mercury (mmHg) increase from baseline, diastolic blood pressure (DBP): >=20 mmHg decrease from baseline; 2) Heart rate (HR): absolute HR > 120 beats per minute (bpm) and >30 bpm increase from baseline, absolute HR <50 bpm and >20 bpm decrease from baseline; 3) Weight: >10% decrease from baseline. Number of participants with any clinically significant change in abnormalities for blood pressure, heart rate and weight are reported in this outcome measure.

  10. Number of Participants With Clinically Significant Change From Baseline in Physical Findings [ Time Frame: Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016]) ]
    Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

  11. Number of Participants With Atleast 1 Concomitant Medication [ Time Frame: From first dose of study drug up to 30 days after the last dose or before initiation of a new anticancer treatment, whichever occurred first (up to the data cutoff date [01 Sep 2016]) ]
    Number of participants taking any non-study medications, therapies, including herbal supplements during the treatment-emergent period for the management of an adverse event or for the treatment of any other disease.

  12. Trough Concentration Versus Time Summary of Talazoparib [ Time Frame: Predose on Day 1 of Cycle 1, 2, 3 and 4 ]
    Concentrations below the limit of quantitation values less than or equal to (<=) 25 picogram per milliliter (pg/mL) were set as zero. Pharmacokinetic (PK) analysis was not done separately for each reporting arm and cohorts were combined for PK analysis.


Other Outcome Measures:
  1. Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016]) ]
    Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the functional status score and global health status/QOL score based on the EORTC-QLQ-C30, whichever occurred first. EORTC-QLQ-C30 questionnaire is a standardized instrument developed to assess the quality of life of people with cancer. EORTC-QLQ-C30 functional subscale includes 5 items: physical, role, emotional, cognitive, and social functioning. All of the single items of functional status subscale measures and global health status/QOL subscale range from 0 to 100, where higher scores represent a better level of functioning/quality of life.

  2. Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) [ Time Frame: Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016]) ]
    Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the symptom score based on the EORTC-QLQ-BR23, whichever occurred first. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much) within each scale.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed carcinoma of the breast
  • Locally advanced and/or metastatic disease
  • Deleterious or pathogenic germline BRCA 1 or BRCA 2 mutation
  • Prior chemotherapy: Cohort 1) PR or CR to prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum; or Cohort 2) > 2 prior chemotherapy regimens for metastatic disease and no prior platinum for metastatic disease
  • ECOG performance status ≤ 1
  • Have adequate organ function

Exclusion Criteria:

  • Prior enrollment into a clinical trial of a PARP inhibitor
  • CNS metastasis except adequately treated brain metastasis documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids for management of CNS symptoms
  • Prior malignancy except for prior BRCA-associated cancer as long as there is no current evidence of the prior cancer, carcinoma in situ of the cervix or non-melanoma skin cancer, and a cancer diagnosed and definitively treated >5 years prior to study enrollment with no subsequent evidence of recurrence
  • Known to be HIV positive, active hepatitis C virus, or active hepatitis B virus
  • Known hypersensitivity to any of the components of talazoparib

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): NCT02034916


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Locations
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United States, California
Marin Cancer Care, Inc.
Greenbrae, California, United States, 94904
UCLA West Medical Pharmacy Attn: Steven L. Wong, PharmD
Los Angeles, California, United States, 90095-1772
UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.
Los Angeles, California, United States, 90095-7349
TRIO-US Central Administration
Los Angeles, California, United States, 90095
Stanford Women's Cancer Center
Palo Alto, California, United States, 94304
UCLA Hematology Oncology- Porter Ranch
Porter Ranch, California, United States, 91326
Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
Redondo Beach, California, United States, 90277
University of California, San Francisco: Helen Diller Comprehensive Cancer Center
San Francisco, California, United States, 94115
UCLA Hematology-Oncology
Santa Monica, California, United States, 90404
Stanford Cancer Institute
Stanford, California, United States, 94305
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Florida
Sylvester at Deerfield Beach
Deerfield Beach, Florida, United States, 33442
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, United States, 33021
Memorial Regional Hospital
Hollywood, Florida, United States, 33021
University of Miami Hospital & Clinics
Miami, Florida, United States, 33136
Memorial Breast Cancer Center at Memorial Hospital West
Pembroke Pines, Florida, United States, 33028
Memorial Cancer Institute at Memorial Hospital West
Pembroke Pines, Florida, United States, 33028
Memorial Hospital West
Pembroke Pines, Florida, United States, 33028
Sylvester at Plantation
Plantation, Florida, United States, 33324
United States, Indiana
ICRC
Indianapolis, Indiana, United States, 46202-5116
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Investigational Drug Services
Indianapolis, Indiana, United States, 46202
IU Health University Hospital
Indianapolis, Indiana, United States, 46202
Sidney & Lois Eskenazi Hospital
Indianapolis, Indiana, United States, 46202
Springmill Medical Clinic
Indianapolis, Indiana, United States, 46290
United States, Maryland
Anne Arundel Medical Center (AAMC), Annapolis Oncology and Hematology
Annapolis, Maryland, United States, 21401
Anne Arundel Medical Center (AAMC), Research Pharmacy
Annapolis, Maryland, United States, 21401
Anne Arundel Medical Center (AAMC)
Annapolis, Maryland, United States, 21401
Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station
Lutherville, Maryland, United States, 21093
United States, New York
Memorial Sloan Kettering Evelyn H. Lauder Breast Center
New York, New York, United States, 10065
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York, United States, 11570
United States, Tennessee
University of Tennessee Medical Center
Knoxville, Tennessee, United States, 37920
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
The Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
France
Centre Oscar Lambret
Lille Cédex, France, 59020
Centre Leon Berard
Lyon Cedex 08, France, 69373
Institut Paoli Calmettes
Marseille, France, 13273 Cedex 9
Hopital Prive du Confluent
Nantes BP 20215, France, 44202 Cedex 2
Hopitaux Universitaires de Strasbourg - Hopital Civil
Strasbourg, France, 67091Cedex
Institut Universitaire du Cancer Toulouse - Oncopole
Toulouse, France, 31059 Cedex 9
CHU Bretonneau Centre Henry Kaplan
Tours Cedex 9, France, 37044
Germany
Universitaetsklinikum Erlangen
Erlangen, Bavaria, Germany, 91054
IOZ Muenchen - lnerdisziplinaeres Onkologisches Zentrum
Muenchen, Bavaria, Germany, 80336
Klinikum rechts der Isar der TU Muenchen
Muenchen, Bavaria, Germany, 81675
University of Munich (LMU) Grosshadern Hospital
Munich, Bavaria, Germany, 81377
Klinikum Mutterhaus Der Borromaeerinnen Ggmbh
Trier, Rheinland-pfalz, Germany, 54290
University Hospital Carl Gustav Carus
Dresden, Saxony, Germany, 01307
Helios Klinikum Berlin-Buch
Berlin, Germany, 13125
University Hospital Duesseldorf
Duesseldorf, Germany, 40225
Kliniken Essen Mitte Klinik fuer Gynaekologie und Gynaekologische Onkologie
Essen, Germany, 45136
Universitaetsklinikum Schleswig-Holstein
Kiel, Germany, 24105
g.SUND Gynaekologie Kompetenzzentrum Stralsund
Stralsund, Germany, 18435
Universitaets-Frauenklinik
Tuebingen, Germany, 72076
Spain
Complejo Hospitalario Universitario A Coruna
A Coruna, Spain, 15006
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Complejo Hospitalario de Jaen
Jaen, Spain, 23007
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
MD Anderson Cancer Center International Espana
Madrid, Spain, 28033
Hospital Clinico San Carlos
Madrid, Spain, 28040
Hospital Universitario San Juan de Alicante
San Juan de Alicante, Spain, 03550
Hospital Universitario Virgen Macarena
Sevilla, Spain, 41009
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
United Kingdom
Cambridge University Hospital NHS Foundation Trust
Cambridge, England, United Kingdom, CB2 0QQ
Sarah Cannon Research Institute UK
London, England, United Kingdom, W1G 6AD
Lancashire Teaching Hospitals NHS Foundation Trust
Preston, Lancashire, United Kingdom, PR2 9HT
The Royal Marsden NHS Foundation Trust
London, United Kingdom, SW3 6JJ
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
The Royal Marsden NHS Foundation Trust
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Pfizer
Myriad Genetic Laboratories, Inc.
Medivation, Inc.
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02034916     History of Changes
Other Study ID Numbers: 673-201
2013-003076-12 ( EudraCT Number )
C3441008 ( Other Identifier: Alias Study Number )
First Posted: January 14, 2014    Key Record Dates
Results First Posted: November 6, 2017
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
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

Keywords provided by Pfizer:
Breast cancer
BRCA mutation
PARP inhibitor
BRCA 1
BRCA 2

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents