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Trial record 1 of 1 for:    NCT02401347
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Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors

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ClinicalTrials.gov Identifier: NCT02401347
Recruitment Status : Recruiting
First Posted : March 27, 2015
Last Update Posted : August 21, 2020
Sponsor:
Collaborators:
BioMarin Pharmaceutical
Pfizer
Information provided by (Responsible Party):
Melinda Telli, Stanford University

Tracking Information
First Submitted Date  ICMJE March 24, 2015
First Posted Date  ICMJE March 27, 2015
Last Update Posted Date August 21, 2020
Study Start Date  ICMJE August 2015
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
Objective response rate (ORR) [ Time Frame: Up to 3 years ]
Objective response rate (ORR) will be assessed and is defined as complete response or partial response per RECIST 1.1
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2015)
Objective response rate defined as complete response or partial response per RECIST 1.1 [ Time Frame: Up to 3 years ]
The objective response and 95% confidence interval will be calculated using the exact binomial model.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • Clinical benefit rate [ Time Frame: After at least 24 weeks ]
    Clinical benefit rate >= 24 weeks will be assessed and is defined as complete response, partial response or stable disease as assessed after at least 24 weeks per RECIST 1.1
  • Progression-free survival (PFS) [ 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2015)
  • 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 ]
    The clinical benefit rate and 95% confidence interval will be calculated using the exact binomial model.
  • Progression-free survival [ Time Frame: From randomization to documented disease progression or death, assessed up to 3 years ]
    Kaplan-Meier curves will be calculated to determine progression-free survival.
  • Incidence of adverse events, graded according to CTCAE v4.0 [ Time Frame: Up to 3 years ]
    Adverse events will be summarized descriptively.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 24, 2015)
  • Deleterious germline mutations in responders and non-responders in Cohort A [ Time Frame: Baseline ]
    Next generation DNA sequencing methods using commercial multiplex panels will be used to assess for deleterious mutations in blood (germline) or tumor tissue (somatic). To compare the proportion of deleterious germline or somatic mutations in responders versus non-responders with triple-negative breast cancer and high HRD scores (Cohort A), Fisher's exact test will be used. The proportion of specific mutations with its 95% confidence interval will be calculated using the exact binomial model.
  • HRD scores in responders and non-responders in Cohort B [ Time Frame: Baseline ]
    Assessed from formalin-fixed, paraffin-embedded (FFPE) tumor tissue using the Myriad HRD assay. Based on prior studies, an HRD cutoff score of 42 or higher will be used to define HR-deficient breast cancer. To compare the HRD scores in the responders versus non-responders with underlying deleterious germline or somatic gene mutations (Cohort B), a two sample t-test will be used.
  • HRD scores of primary tumor tissue and metastatic tumor tissue [ Time Frame: Baseline ]
    Assessed from FFPE tumor tissue using the Myriad HRD assay. To assess the concordance of the HRD scores in the primary tumor tissue with that in the metastatic tumor tissue, a paired t-test will be used.
 
Descriptive Information
Brief Title  ICMJE Phase II Trial of Talazoparib in BRCA1/2 Wild-type HER2-negative Breast Cancer and Other Solid Tumors
Official Title  ICMJE 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
Brief 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.
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Breast Cancer
  • HER2/Neu Negative
  • Triple-Negative Breast Cancer
Intervention  ICMJE Drug: Talazoparib Tosylate
Participants receive Talazoparib tosylate at 1 mg by mouth daily.
Other Name: BMN 673
Study Arms  ICMJE
  • Experimental: Cohort A - Triple-negative Breast Cancer

    Participants 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.

    Intervention: Drug: Talazoparib Tosylate
  • Experimental: Cohort B - HER2-negative solid tumor

    Participants 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.

    Intervention: Drug: Talazoparib Tosylate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2019)
40
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2015)
58
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  • 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
  • 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.

EXCLUSION CRITERIA:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wyatt F Gross 650-721-4076 wgross@stanford.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02401347
Other Study ID Numbers  ICMJE IRB-31913
NCI-2015-00036 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
BRS0050 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Melinda Telli, Stanford University
Study Sponsor  ICMJE Melinda Telli
Collaborators  ICMJE
  • BioMarin Pharmaceutical
  • Pfizer
Investigators  ICMJE
Principal Investigator: Melinda L. Telli, M.D. Stanford University
PRS Account Stanford University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP