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Talazoparib Before Standard Therapy in Treating Patients With Invasive, BRCA-Mutated Breast Cancer

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ClinicalTrials.gov Identifier: NCT02282345
Recruitment Status : Active, not recruiting
First Posted : November 4, 2014
Last Update Posted : August 22, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the side effects of talazoparib when given before standard therapy in treating patients with breast cancer that has spread to nearby healthy tissue and has a mutation in a breast cancer, early onset (BRCA) gene. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may be especially effective in patients with BRCA mutations. It is not yet known whether adding talazoparib before standard treatment is safe in treating patients with BRCA mutated breast cancer.

Condition or disease Intervention/treatment Phase
Breast Adenocarcinoma Deleterious BRCA1 Gene Mutation Deleterious BRCA2 Gene Mutation HER2/Neu Negative Invasive Breast Carcinoma Other: Laboratory Biomarker Analysis Drug: Talazoparib Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of using talazoparib prior to initiating standard neoadjuvant therapies.

II. To evaluate the toxicity profile in women taking talazoparib in the neoadjuvant setting.

SECONDARY OBJECTIVES:

I. To provide first estimate of clinical response to talazoparib in the neoadjuvant setting in a pilot trial setting.

II. To evaluate biomarkers of therapy efficacy as well as initiate patient derived xenograft (PDX) models: targeted or whole exome sequencing for BRCA pathway mutations and other somatic and germline alterations; ribonucleic acid (RNA) sequencing; evaluation of changes in immune response; transcriptional profile to assess triple negative breast cancer (TNBC) subtype, BRCA-ness signature and putative PARP sensitivity predictors; functional proteomics with reverse phase protein array (RPPA); generate PDX models and mammosphere cultures from patient derived tumors; PTEN, gamma-H2A histone family, member x (gamma-H2A.X), Ki-67 and cleaved caspase 3 by immunohistochemistry (IHC).

OUTLINE:

Patients receive talazoparib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice.

After completion of study treatment, patients are followed up until the day after definitive breast surgery.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Talazoparib as a Neoadjuvant Study in Patients With a Diagnosis of Invasive Breast Cancer and a Deleterious BRCA Mutation
Actual Study Start Date : April 16, 2015
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Treatment (talazoparib)

Patients receive talazoparib PO QD on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then proceed to the standard of care therapy of the treating physician's choice.

This arm was concluded early after 13 patients. An expansion arm of 20 patients was opened in August 2016 to include at least 4 and up to 6 cycles of talazoparib, followed by surgery to estimate residual cancer burden after therapy with single-agent talazoparib.

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Talazoparib
Given PO
Other Names:
  • BMN 673
  • BMN-673




Primary Outcome Measures :
  1. Number of patients enrolled [ Time Frame: Up to 2 years from initiating accrual ]
    Feasibility will be considered to be achieved if the treatment is safe and all 20 patients are able to be accrued within 2 years from initiating accrual-this was concluded after 13 patients due to favorable toxicity and ability to accrue 13 patients in 8 months. The expansion phase of the trial opened in August 2016 and will accrue 20 patients.

  2. Toxicity rate of talazoparib [ Time Frame: Up to week 9 ]
    Aggregate toxicity rate will be monitored. Feasibility will be considered to be achieved if the treatment is safe and all 20 patients are able to be accrued within 2 years from initiating accrual. If greater than 33% of the patients enrolled have either a grade 4 toxicity attributable to the treatment, or require a delay in treatment for greater than 4 weeks due to toxicity, trial accrual will be suspended. As there were no grade 4 toxicities identified in the first 13 patients, this was concluded early. In the 20 patient expansion phase, toxicity and dose reductions will continue to be monitored.



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

Inclusion Criteria:

  • Signed written informed consent
  • Histologically confirmed primary invasive adenocarcinoma of the breast with the size of the primary tumor being at least 1 cm on imaging by either mammography, ultrasound or breast magnetic resonance imaging (MRI)
  • Negative human epidermal growth factor receptor 2 (HER-2)/neu- disease defined as patients with fluorescence in situ hybridization (FISH) ratio < 2.0 or < 6.0 HER2 gene copies per nucleus, and IHC staining scores of 0, 1+, or 2+
  • No treatment for current primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, immunotherapy, investigational therapy or surgery; previous treatment for breast and/or ovarian cancer with chemotherapy, endocrine therapy, surgery and radiation are allowed if >= 3 years prior to current diagnosis and there is no clinical evidence of metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Baseline multi gated acquisition scan (MUGA) or echocardiogram scans with left ventricular ejection fraction (LVEF) of > 50%
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin (Hgb) >= 9 g/dL
  • Creatinine clearance > 50 ml/min
  • Total bilirubin =< 1.5 X upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X ULN
  • Negative serum or urine pregnancy test for women within 7 days of receiving the first dose of the study medication for women of childbearing potential; women will be considered not of childbearing potential and exempt from pregnancy testing if they are either a) older than 50 and amenorrheic for at least 12 consecutive months following cessation of all exogenous hormonal treatments, or b) have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product; men on study also must be using contraception
  • Identified deleterious mutation in BRCA 1 or 2 genes (this does not include variants of uncertain significance)
  • Eligible to receive standard of care chemotherapy and/or surgery based upon standard practices or institutional guidelines

Exclusion Criteria:

  • Women who are pregnant (including positive pregnancy test at enrollment or prior to study drug administration) or breast-feeding
  • Disease free of prior malignancy for < 3 years with the exception of curatively treated basal carcinoma of the skin or carcinoma in situ of the cervix
  • Any other previous antitumor therapies for the current cancer event
  • Has had major surgery within 21 days before cycle 1 day 1
  • Gastrointestinal tract disease or defect with associated malabsorption syndrome
  • Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication
  • Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy
  • Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols
  • Unable to take oral medications
  • Known to be human immunodeficiency virus positive
  • Known active hepatitis C virus, or known active hepatitis B virus
  • 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 (v)4.03 or requiring the use of parenteral anti-microbial agents within 14 days before day 1 of study drug
    • Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
    • Non-healing wound, ulcer, or bone fracture
  • Known hypersensitivity to any of the components of talazoparib

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): NCT02282345


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jennifer K Litton M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02282345     History of Changes
Other Study ID Numbers: 2014-0045
NCI-2015-00335 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0045 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: November 4, 2014    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Breast Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents