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)
- Conditions
- Breast NeoplasmsBRCA 1 Gene MutationBRCA 2 Gene Mutation
- Interventions
- Registration Number
- NCT02034916
- Lead Sponsor
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 84
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description talazoparib 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
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) 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
Name Time Method Number of Participants With Outcome in Response to Adverse Events (AEs) Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018) 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'.
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018) Laboratory tests included hematology (hemoglobin \[low\], leucocytes \[low\], lymphocytes \[low\], neutrophils \[low\], platelets \[low\]). 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 laboratory parameter is reported in this outcome measure.
Clinical Benefit Rate-24 (CBR-24) 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.
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]) 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.
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) 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.
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]) 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.
Overall Survival (OS) 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.
Number of Participants With Treatment-Related 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) 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. Related TEAEs are TEAEs that were judged by the investigators as possibly, probably, or definitely related to study drug. AEs included both SAES and non SAES.
Trough Concentration Versus Time Summary of Talazoparib Predose on Day 1 of Cycle 1, 2, 3, and 4 (data cutoff date: 01 Sep 2016) 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.
Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) 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 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 chemistry laboratory parameter is reported in this outcome measure.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018) Criteria for clinically significant vital signs changes: 1) Blood pressure: systolic blood pressure (SBP): greater than or equal to (\>=30) millimeters of mercury (mmHg) increase from baseline, diastolic blood pressure (DBP): \>=20 mmHg decrease from baseline; 2) Heart rate (HR): absolute HR greater than (\>) 120 beats per minute (bpm) and \>30 bpm increase from baseline, absolute HR less than (\<) 50 bpm and \>20 bpm decrease from baseline; 3) Weight: \>10% decrease from baseline. Number of participants with any clinically significant change from baseline for blood pressure, heart rate and weight are reported in this outcome measure.
Number of Participants With Clinically Significant Change From Baseline in Physical Findings Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018) 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.
Number of Participants With At Least 1 Concomitant Medication Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018) 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.
Trial Locations
- Locations (70)
Marin Cancer Care, Inc.
🇺🇸Greenbrae, California, United States
UCLA Hematology-Oncology
🇺🇸Santa Monica, California, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Anne Arundel Medical Center (AAMC), Annapolis Oncology and Hematology
🇺🇸Annapolis, Maryland, United States
Anne Arundel Medical Center (AAMC), Research Pharmacy
🇺🇸Annapolis, Maryland, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Centre Oscar Lambret
🇫🇷Lille Cédex, France
Institut Paoli Calmettes
🇫🇷Marseille, France
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Indiana University Health Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
IU Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Springmill Medical Clinic
🇺🇸Indianapolis, Indiana, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.
🇺🇸Los Angeles, California, United States
Stanford Women's Cancer Center
🇺🇸Palo Alto, California, United States
UCLA Hematology Oncology- Porter Ranch
🇺🇸Porter Ranch, California, United States
Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
🇺🇸Redondo Beach, California, United States
Investigational Drug Services
🇺🇸Indianapolis, Indiana, United States
Sidney & Lois Eskenazi Hospital
🇺🇸Indianapolis, Indiana, United States
Memorial Sloan Kettering Evelyn H. Lauder Breast Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Rockville Centre
🇺🇸Rockville Centre, New York, United States
Universitaets-Frauenklinik
🇩🇪Tuebingen, Germany
Anne Arundel Medical Center (AAMC)
🇺🇸Annapolis, Maryland, United States
CHU Bretonneau Centre Henry Kaplan
🇫🇷Tours Cedex 9, France
IOZ Muenchen - lnerdisziplinaeres Onkologisches Zentrum
🇩🇪Muenchen, Bavaria, Germany
Sylvester at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Centre Leon Berard
🇫🇷Lyon Cedex 08, France
University Hospital Duesseldorf
🇩🇪Duesseldorf, Germany
Universitaetsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Memorial Cancer Institute at Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station
🇺🇸Lutherville, Maryland, United States
Universitaetsklinikum Erlangen
🇩🇪Erlangen, Bavaria, Germany
University Hospital Carl Gustav Carus
🇩🇪Dresden, Saxony, Germany
Sylvester at Plantation
🇺🇸Plantation, Florida, United States
Institut Universitaire du Cancer Toulouse - Oncopole
🇫🇷Toulouse, France
Klinikum Mutterhaus Der Borromaeerinnen Ggmbh
🇩🇪Trier, Rheinland-pfalz, Germany
Kliniken Essen Mitte Klinik fuer Gynaekologie und Gynaekologische Onkologie
🇩🇪Essen, Germany
University of Miami Hospital & Clinics
🇺🇸Miami, Florida, United States
Cambridge University Hospital NHS Foundation Trust
🇬🇧Cambridge, England, United Kingdom
Sarah Cannon Research Institute UK
🇬🇧London, England, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust
🇬🇧Preston, Lancashire, United Kingdom
UCLA West Medical Pharmacy Attn: Steven L. Wong, PharmD
🇺🇸Los Angeles, California, United States
TRIO-US Central Administration
🇺🇸Los Angeles, California, United States
University of California, San Francisco: Helen Diller Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
ICRC
🇺🇸Indianapolis, Indiana, United States
Hopital Prive du Confluent
🇫🇷Nantes BP 20215, France
Hopitaux Universitaires de Strasbourg - Hopital Civil
🇫🇷Strasbourg, France
Klinikum rechts der Isar der TU Muenchen
🇩🇪Muenchen, Bavaria, Germany
g.SUND Gynaekologie Kompetenzzentrum Stralsund
🇩🇪Stralsund, Germany
Complejo Hospitalario Universitario A Coruna
🇪🇸A Coruna, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Complejo Hospitalario de Jaen
🇪🇸Jaen, Spain
MD Anderson Cancer Center International Espana
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario San Juan de Alicante
🇪🇸San Juan de Alicante, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Memorial Cancer Institute at Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Memorial Breast Cancer Center at Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Helios Klinikum Berlin-Buch
🇩🇪Berlin, Germany
University of Munich (LMU) Grosshadern Hospital
🇩🇪Munich, Bavaria, Germany