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
|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|
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.
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).
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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.
- 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.
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
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jennifer K Litton||M.D. Anderson Cancer Center|