Clinical trial NCT02034916: 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)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Neoplasms
BRCA 1 Gene Mutation
BRCA 2 Gene Mutation
Keywords: Breast cancer
BRCA mutation
PARP inhibitor
BRCA 1
BRCA 2
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Myriad Genetic Laboratories, Inc.
name: Medivation, Inc.
First posted: 2014-01-14
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From randomization until data cutoff date (01 Sep 2016)
Secondary outcomes:
measure: Clinical Benefit Rate-24 (CBR-24)
timeFrame: From randomization until data cutoff date (01 Sep 2016)
measure: Duration of Response (DOR)
timeFrame: 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])
measure: Progression Free Survival (PFS)
timeFrame: 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])
measure: Overall Survival (OS)
timeFrame: From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016])
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Number of Participants With Outcome in Response to Adverse Events (AEs)
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter)
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter)
timeFrame: 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])
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Number of Participants With Clinically Significant Change From Baseline in Physical Findings
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Number of Participants With At Least 1 Concomitant Medication
timeFrame: Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)
measure: Trough Concentration Versus Time Summary of Talazoparib
timeFrame: Predose on Day 1 of Cycle 1, 2, 3, and 4 (data cutoff date: 01 Sep 2016)
Other outcomes:
measure: 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)
timeFrame: 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])
measure: 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)
timeFrame: 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])
Locations:
city: Greenbrae
country: United States
facility: Marin Cancer Care, Inc.
state: California
city: Los Angeles
country: United States
facility: UCLA West Medical Pharmacy Attn: Steven L. Wong, PharmD
state: California
city: Los Angeles
country: United States
facility: UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.
state: California
city: Los Angeles
country: United States
facility: TRIO-US Central Administration
state: California
city: Palo Alto
country: United States
facility: Stanford Women's Cancer Center
state: California
city: Porter Ranch
country: United States
facility: UCLA Hematology Oncology- Porter Ranch
state: California
city: Redondo Beach
country: United States
facility: Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco: Helen Diller Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology-Oncology
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Deerfield Beach
country: United States
facility: Sylvester at Deerfield Beach
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital & Clinics
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Breast Cancer Center at Memorial Hospital West
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute at Memorial Hospital West
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Hospital West
state: Florida
city: Plantation
country: United States
facility: Sylvester at Plantation
state: Florida
city: Indianapolis
country: United States
facility: ICRC
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Drug Services
state: Indiana
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Sidney & Lois Eskenazi Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Springmill Medical Clinic
state: Indiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center (AAMC), Annapolis Oncology and Hematology
state: Maryland
city: Annapolis
country: United States
facility: Anne Arundel Medical Center (AAMC), Research Pharmacy
state: Maryland
city: Annapolis
country: United States
facility: Anne Arundel Medical Center (AAMC)
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins
state: Maryland
city: Lutherville
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Evelyn H. Lauder Breast Center
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 Rockville Centre
state: New York
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Lille Cédex
country: France
facility: Centre Oscar Lambret
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes BP 20215
country: France
facility: Hopital Prive du Confluent
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg - Hopital Civil
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole
city: Tours Cedex 9
country: France
facility: CHU Bretonneau Centre Henry Kaplan
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
state: Bavaria
city: Muenchen
country: Germany
facility: IOZ Muenchen - lnerdisziplinaeres Onkologisches Zentrum
state: Bavaria
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
state: Bavaria
city: Munich
country: Germany
facility: University of Munich (LMU) Grosshadern Hospital
state: Bavaria
city: Trier
country: Germany
facility: Klinikum Mutterhaus Der Borromaeerinnen Ggmbh
state: Rheinland-pfalz
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
state: Saxony
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch
city: Duesseldorf
country: Germany
facility: University Hospital Duesseldorf
city: Essen
country: Germany
facility: Kliniken Essen Mitte Klinik fuer Gynaekologie und Gynaekologische Onkologie
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Stralsund
country: Germany
facility: g.SUND Gynaekologie Kompetenzzentrum Stralsund
city: Tuebingen
country: Germany
facility: Universitaets-Frauenklinik
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center International Espana
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: San Juan de Alicante
country: Spain
facility: Hospital Universitario San Juan de Alicante
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: England
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
state: Lancashire
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.