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Trial record 1 of 1 for:    NCT02401347 | Breast Cancer
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Talazoparib Beyond BRCA (TBB) Trial

This study is currently recruiting participants.
Verified August 2015 by Melinda Telli, Stanford University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02401347
First Posted: March 27, 2015
Last Update Posted: August 11, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Melinda Telli, Stanford University
  Purpose
The aim of this single-arm phase II clinical trial is to evaluate the anti-cancer activity of Talazoparib (also known as BMN 673) in patients with advanced breast cancer with specific genetic or tumor genomic alterations. Patients with either triple-negative or HER2-negative breast cancer are eligible.

Condition Intervention Phase
Advanced Breast Cancer HER2/Neu Negative Triple-Negative Breast Cancer Drug: Talazoparib Tosylate Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial of BMN 673 in BRCA1 and BRCA2 Wild-Type Patients With (i) Advanced Triple-Negative Breast Cancer and Homologous Recombination Deficiency as Assessed by the HRD Assay, and (ii) Advanced HER2-Negative Breast Cancer With Either a Germline or Somatic Mutation in Homologous Recombination Pathway Genes

Resource links provided by NLM:


Further study details as provided by Melinda Telli, Stanford University:

Primary Outcome Measures:
  • Objective response rate defined as complete response or partial response per RECIST 1.1 [ Time Frame: Up to 3 years ]

Secondary Outcome Measures:
  • Clinical benefit rate >= 24 weeks, defined as complete response, partial response or stable disease as assessed after at least 24 weeks per RECIST 1.1 [ Time Frame: After at least 24 weeks ]
  • Progression-free survival [ Time Frame: From randomization to documented disease progression or death ]
  • Incidence of adverse events, graded according to CTCAE v4.0 [ Time Frame: Up to 3 years ]

Estimated Enrollment: 58
Study Start Date: August 2015
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A

Patients with advanced triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD) based on the Myriad HRD Assay.

Patients receive Talazoparib 1 mg by mouth daily.

Drug: Talazoparib Tosylate
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
Other Name: BMN 673
Experimental: Cohort B

Patients with advanced HER2-negative breast cancer with a deleterious hereditary or cancer somatic mutation in one of the following genes:

PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes.

Patients receive Talazoparib 1 mg by mouth daily.

Drug: Talazoparib Tosylate
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
Other Name: BMN 673

Detailed Description:

Talazoparib (BMN 673) is a novel, dual-mechanism PARP inhibitor that potently inhibits the PARP enzyme and effectively traps PARP on DNA. Talazoparib has shown promising single-agent anti-tumor efficacy in several BRCA1/2 mutation-associated advanced cancers. The efficacy of PARP inhibition in BRCA1/2 wild-type TNBC with homologous recombination (HR) defects and in breast tumors with mutations in other non-BRCA1/2 HR pathway genes is currently unknown.

This Phase 2 trial (TBB) explores the activity of single agent talazoparib in BRCA1/2 wild-type BC patients using an optimal Simon two-stage design. Eligible subjects will be assigned to one of two parallel cohorts: 1) Cohort A: Subjects (n=29) with advanced TNBC with underlying HR defects as assessed by the HRD assay and, 2) Cohort B: Subjects (n=29) with advanced HER2-negative BC with a somatic or germline mutation in a non-BRCA1/2 HR pathway gene. Gene mutations of interest are: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes (FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL).

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

  • No deleterious germline BRCA1 or BRCA2 mutation based on full sequencing and comprehensive rearrangement testing at an external reference laboratory (Myriad Genetics); patients with variants of unknown significance will be eligible
  • Patients must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Must have progressed on at least 1 prior chemotherapy regimen for the treatment of advanced breast cancer; there is no upper limit on the number of prior therapies
  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • An estimated life expectancy of at least 16 weeks
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT =< 5 x ULN
  • Total serum bilirubin =< 1.5 x ULN (=< 3 x ULN for Gilbert's syndrome)
  • Calculated creatinine clearance >= 30 mL/min or serum creatinine =< 1.5 mg/dl
  • Hemoglobin >= 9.0 g/dL with last transfusion at least 14 days before day 1 of study drug
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Able to take oral medications
  • Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
  • Sexually active patients of childbearing potential must be willing to use an acceptable method of contraception such as an intrauterine device or double barrier contraception during treatment and for 30 days after the last dose of study drug
  • Females of childbearing potential must have a negative serum pregnancy test at screening and be willing to have additional serum pregnancy tests during the study; females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy
  • Willing and able to comply with all study procedures
  • COHORT A SPECIFIC ELIGIBILITY CRITERIA:

    • Histologically confirmed metastatic or recurrent triple-negative breast cancer (defined as estrogen receptor =< 5%, progesterone receptor =< 5%, HER2-negative via immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH])
    • An HRD score >= 42 on the Myriad HRD Assay as assessed on a tumor biopsy sample; in the case that obtaining an adequate metastatic tumor biopsy is not possible, we will assess the HRD score from the primary breast tumor
  • COHORT B SPECIFIC ELIGIBILITY CRITERIA:

    • Histologically confirmed metastatic or recurrent HER2-negative (via IHC or FISH) breast cancer
    • Deleterious germline or somatic mutation implicated in the homologous recombination (HR) pathway, excluding BRCA1 or BRCA2, based on germline multiplex gene testing or direct tumor next generation DNA sequencing. Genes of interest include: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, Rad51c, Rad51d, MRE11, ATR, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, plus other HR-related genes at the discretion of the primary investigators.

Exclusion Criteria:

  • Any patient with a deleterious mutation in BRCA1 or BRCA2
  • Prior treatment with a platinum agent (i.e. cisplatin or carboplatin)
  • Prior treatment with a PARP inhibitor
  • Non-measurable disease only
  • Pregnant or nursing patients
  • Any anti-cancer therapy within the past 21 days of the first day of treatment
  • Brain or central nervous system (CNS) metastases that are progressive or symptomatic, have not been previously resected or irradiated, or are the only site of measurable disease
  • Other malignancy that is either active or for which patient has received treatment in the last five years excluding non-melanoma skin cancer and carcinoma in situ of the cervix
  • Radiation therapy in the last 14 days
  • Known to be human immunodeficiency virus positive
  • Known active hepatitis C virus, or known active hepatitis B virus
  • Use of any investigational product (IP) or investigational medical device within 28 days before day 1 of study drug
  • Major surgery requiring a prolonged hospitalization or recovery within 21 days before day 1 of study drug
  • Concurrent disease or condition that would interfere with study participation or safety, such as any of the following:

    • Active, clinically significant infection either grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 or requiring the use of parenteral anti-microbial agents within 7 days before day 1 of study drug
    • Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
    • Known hypersensitivity to any of the components of BMN 673
  Contacts and Locations
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): NCT02401347


Locations
United States, California
Stanford University Hospitals and Clinics Recruiting
Stanford, California, United States, 94305
Contact: Pei Jen Chang    650-725-0866    peijenc@stanford.edu   
Principal Investigator: Melinda L. Telli, M.D.         
Sponsors and Collaborators
Melinda Telli
National Cancer Institute (NCI)
Investigators
Principal Investigator: Melinda L. Telli, M.D. Stanford University
  More Information

Responsible Party: Melinda Telli, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT02401347     History of Changes
Other Study ID Numbers: BRS0050
NCI-2015-00036 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
BRS0050 ( Other Identifier: Stanford University Hospitals and Clinics )
P30CA124435 ( U.S. NIH Grant/Contract )
First Submitted: March 24, 2015
First Posted: March 27, 2015
Last Update Posted: August 11, 2015
Last Verified: August 2015

Keywords provided by Melinda Telli, Stanford University:
PALB2 mutation
BRIP1 mutation
BARD1 mutation
Rad51c mutation
PTEN mutation
CHEK2 mutation
ATM mutation
NBN mutation
Rad51d mutation
Rad50 mutation
MRE11 mutation
FANC mutation
HRD assay score
ATR mutation

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative 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