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Advanced Breast CancerPhase 2NCT02401347

Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors

A Phase 2 study testing Talazoparib Tosylate in people with Advanced Breast Cancer and HER2/Neu Negative, run by Melinda Telli at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this single-arm phase 2 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Talazoparib Tosylate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
Aug 2015to Dec 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • No deleterious germline BRCA1 or BRCA2 mutation based on full sequencing and comprehensive rearrangement testing at an external reference laboratory; patients with variants of unknown significance will be eligible
  • Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 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
  • If prior platinum agent (eg, carboplatin or cisplatin) has been administered, no evidence of progression, or within 8 weeks of stopping platinum treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • 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
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  • 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 homologous recombination deficiency (HRD) score ≥ 42 on the 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 or other histologically-confirmed metastatic solid tumor
  • 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.

Who cannot join

  • Any patient with a deleterious mutation in BRCA1 or BRCA2
  • Hormone receptor positive and/or HER2 positive breast cancer (Cohort A only)
  • HER2 positive breast cancer (Cohort B only)
  • Prior treatment with a PARP inhibitor
  • Non-measurable disease only
  • Pregnant or nursing patients
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  • Any anti-cancer therapy within the past 21 days of the first day of treatment
  • Brain or central nervous system (CNS) metastases
  • Exception: Adequately treated brain metastases documented by baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan that have not progressed since previous scans and do not require corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of CNS symptoms. A repeated CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases
  • Subjects with leptomeningeal carcinomatosis are not permitted
  • 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
  • Known active hepatitis B virus
  • Use of any investigational product 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Stanford Medicine at Stanford University

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase II Clinical Trial of the PARP Inhibitor Talazoparib in BRCA1 and BRCA2 Wild Type Patients With Advanced Triple Negative Breast Cancer and Homologous Recombination Deficiency or Advanced HER2 Negative Breast Cancer or Other Solid Tumors With a Mutation in Homologous Recombination Pathway Genes

The aim of this single-arm phase 2 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.

Read the 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 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).

Being tested
Talazoparib Tosylate
Keywords
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
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Talazoparib TosylateDrug

    Also called BMN 673

    Participants receive Talazoparib tosylate at 1 mg by mouth daily.

Study groups in NCT02401347
Study groupRoleWhat they receive
Cohort A - Triple-negative Breast CancerExperimentalParticipants with advanced triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD) based on the Myriad HRD Assay. Participants receive talazoparib 1 mg by mouth daily.
Receives: Drug: Talazoparib Tosylate
Cohort B - HER2-negative solid tumorExperimentalParticipants with advanced HER2-negative solid tumor 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. Participants receive talazoparib 1 mg by mouth daily.
Receives: Drug: Talazoparib Tosylate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response (OR)

    Objective response (OR) is a common measure of benefit. OR is defined as the number of participants who achieved complete response (CR) or partial clinical (PR), per the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (v1.1). RECIST Criteria are assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays, as follows:

    • CR = Disappearance of all target and non-target lesions
    • PR = ≥30% decrease in the sum of the long diameter of target lesions
    • OR = CR+PR
    • Stable disease (SD) = Small changes that do not meet any of the above criteria
    • Progressive disease (PD) = ≥20% increase in long diameter of target lesions, and/or the appearance of any new lesion(s) The outcome is expressed as the number of participants that achieved either CR or PR within 24 weeks of the start of treatment, a number without dispersion.

    Measured: up to 24 weeks

Secondary outcomes (2)
  1. Clinical Benefit (CB)

    Clinical benefit (CB) is a common measure of benefit. CB is defined as the number of participants who achieved complete response (CR); partial clinical (PR); or stable disease (SD), per the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (v1.1). RECIST Criteria are assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays, as follows:

    • CR = Disappearance of all target and non-target lesions
    • PR = ≥30% decrease in the sum of the long diameter of target lesions
    • SD = Small changes that do not meet any of the above criteria
    • CB = CR+PR+SD
    • Progressive disease (PD) = ≥20% increase in long diameter of target lesions, and/or the appearance of any new lesion(s) The outcome is expressed as the number of participants that achieved either CR, PR, or SD within 24 weeks of the start of treatment, a number without dispersion.

    Measured: up to 24 weeks

  2. Progression-free Survival (PFS)

    Progression-free survival (PFS) is a common measure of benefit. PFS means to remain alive with disease or tumor progression. Progression was defined per the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (v1.1) as any ≥20% increase in long diameter of the target lesions, and/or the appearance of any new lesion(s). PFS is expressed as the number of participants who remained alive without progression after 1 year, a number without dispersion.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2015 (estimated)
  2. Study startAug 2015
  3. Primary completion23 Dec 2019
  4. Study completionDec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02401347
Sponsor's protocol ID
IRB-31913
Other IDs
NCI-2015-00036, BRS0050
Status last verified
Feb 2023
First submitted
24 Mar 2015
Last updated
21 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gruber JJ, Afghahi A, Timms K, DeWees A, Gross W, Aushev VN, Wu HT, Balcioglu M, Sethi H, Scott D, Foran J, McMillan A, Ford JM, Telli ML. A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes. Nat Cancer. 2022 Oct;3(10):1181-1191. doi: 10.1038/s43018-022-00439-1. Epub 2022 Oct 17.

    PubMed 36253484

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Talazoparib Tosylate in people with Advanced Breast Cancer and HER2/Neu Negative, run by Melinda Telli at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response (OR) (time frame: up to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02401347, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.

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