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)

NCT02034916 | Terminated Phase 2 Results

• 3 other identifiers: 673-2012013-003076-12C3441008
• Study Type: interventional
• Target: 84
• Locations: 5 countries
• Sites: 71

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

Conditions

Breast Neoplasms; BRCA 1 Gene Mutation; BRCA 2 Gene Mutation

Keywords

Breast cancer; BRCA mutation; PARP inhibitor; BRCA 1; BRCA 2

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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).

  From randomization until data cutoff date (01 Sep 2016)

Secondary Outcomes (13)

• Clinical Benefit Rate-24 (CBR-24)

  From randomization until data cutoff date (01 Sep 2016)

• Duration of Response (DOR)

  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])

• Progression Free Survival (PFS)

  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])

• Overall Survival (OS)

  From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016])

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Other Outcomes (2)

• 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)

  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 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)

  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])

Study Arms (1)

talazoparib

EXPERIMENTAL

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

Interventions

talazoparib DRUG

Also known as: MDV3800, BMN673

talazoparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead
• Myriad Genetic Laboratories, Inc.: collaborator
• Medivation, Inc.: collaborator

Study Sites (71)

Marin Cancer Care, Inc.

Greenbrae, California, 94904, United States

Location

UCLA West Medical Pharmacy Attn: Steven L. Wong, PharmD

Los Angeles, California, 90095-1772, United States

Location

UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.

Los Angeles, California, 90095-7349, United States

Location

TRIO-US Central Administration

Los Angeles, California, 90095, United States

Location

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

Location

UCLA Hematology Oncology- Porter Ranch

Porter Ranch, California, 91326, United States

Location

Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates

Redondo Beach, California, 90277, United States

Location

University of California, San Francisco: Helen Diller Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

UCLA Hematology-Oncology

Santa Monica, California, 90404, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Sylvester at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

University of Miami Hospital & Clinics

Miami, Florida, 33136, United States

Location

Memorial Breast Cancer Center at Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

Location

Memorial Cancer Institute at Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

Location

Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

Location

Sylvester at Plantation

Plantation, Florida, 33324, United States

Location

ICRC

Indianapolis, Indiana, 46202-5116, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Investigational Drug Services

Indianapolis, Indiana, 46202, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Sidney & Lois Eskenazi Hospital

Indianapolis, Indiana, 46202, United States

Location

Springmill Medical Clinic

Indianapolis, Indiana, 46290, United States

Location

Anne Arundel Medical Center (AAMC), Annapolis Oncology and Hematology

Annapolis, Maryland, 21401, United States

Location

Anne Arundel Medical Center (AAMC), Research Pharmacy

Annapolis, Maryland, 21401, United States

Location

Anne Arundel Medical Center (AAMC)

Annapolis, Maryland, 21401, United States

Location

Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station

Lutherville, Maryland, 21093, United States

Location

Memorial Sloan Kettering Evelyn H. Lauder Breast Center

New York, New York, 10065, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Centre Oscar Lambret

Lille Cédex, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273 Cedex 9, France

Location

Hopital Prive du Confluent

Nantes BP 20215, 44202 Cedex 2, France

Location

Hopitaux Universitaires de Strasbourg - Hopital Civil

Strasbourg, 67091Cedex, France

Location

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059 Cedex 9, France

Location

CHU Bretonneau Centre Henry Kaplan

Tours, 37044, France

Location

Universitaetsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

IOZ Muenchen - lnerdisziplinaeres Onkologisches Zentrum

Munich, Bavaria, 80336, Germany

Location

University of Munich (LMU) Grosshadern Hospital

Munich, Bavaria, 81377, Germany

Location

Klinikum rechts der Isar der TU Muenchen

Munich, Bavaria, 81675, Germany

Location

Klinikum Mutterhaus Der Borromaeerinnen Ggmbh

Trier, Rhineland-Palatinate, 54290, Germany

Location

University Hospital Carl Gustav Carus

Dresden, Saxony, 01307, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

University Hospital Duesseldorf

Düsseldorf, 40225, Germany

Location

Kliniken Essen Mitte Klinik fuer Gynaekologie und Gynaekologische Onkologie

Essen, 45136, Germany

Location

Universitaetsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

g.SUND Gynaekologie Kompetenzzentrum Stralsund

Stralsund, 18435, Germany

Location

Universitaets-Frauenklinik

Tübingen, 72076, Germany

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Complejo Hospitalario de Jaen

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

MD Anderson Cancer Center International Espana

Madrid, 28033, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario San Juan de Alicante

Sant Joan d'Alacant, 03550, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Cambridge University Hospital NHS Foundation Trust

Cambridge, England, CB2 0QQ, United Kingdom

Location

Sarah Cannon Research Institute UK

London, England, W1G 6AD, United Kingdom

Location

Lancashire Teaching Hospitals NHS Foundation Trust

Preston, Lancashire, PR2 9HT, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Turner NC, Laird AD, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmana J, Fasching PA, Hurvitz SA, Hopkins JF, Albacker LA, Chelliserry J, Chen Y, Conte U, Wardley AM, Robson ME. Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study. NPJ Breast Cancer. 2023 Oct 6;9(1):81. doi: 10.1038/s41523-023-00561-y.

  PMID: 37803017 DERIVED

• Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmana J, Fasching PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME; ABRAZO Study Group. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res. 2019 May 1;25(9):2717-2724. doi: 10.1158/1078-0432.CCR-18-1891. Epub 2018 Dec 18.

  PMID: 30563931 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: January 14, 2014
• Study Start: December 13, 2013
• Primary Completion: September 1, 2016
• Study Completion: October 31, 2018
• Last Updated: October 14, 2019
• Results First Posted: November 6, 2017

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (12); US (37); GB (6); ES (9); FR (7)