A randomized phase II clinical trial of talazoparib maintenance therapy in triple-negative breast cancer patients who showed platinum-sensitivity on first- or second-line platinum-based chemotherapy
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- Female
- Target Recruitment
- 206
1) Histologically or cytologically confirmed triple-negative breast cancer patients who are receiving primary or secondary chemotherapy for recurrent, metastatic, or unresectable disease. Triple negative breast cancer is defined as ER negative, PR negative, and HER2 negative receptor status.
(1) ER negative and PR negative are defined as less than 1% of immunohistochemistry (IHC) nuclear staining.
(2) HER2 negative is defined by the following criteria
- IHC 0, 1+ and no in-situ hybridization (ISH) result, or
- IHC 2+ and ISH negative (average HER2 gene copy number <4 signals/cell in single-probe ISH or HER2/CEP17 ratio <2.0 and average HER2 gene copy number <4 signals/cell in dual-probe ISH) or
- No IHC and negative ISH
2) Female patients over 19 years old
3) Patients undergoing primary or secondary platinum-based (Cisplatin or Carboplatin) chemotherapy for recurrent, metastatic, or unresectable triple-negative breast cancer, who exhibit platinum sensitivity during chemotherapy.
*Platinum-based chemotherapy administered before clinical trial administration is Carboplatin administered as a combination therapy with a combination partner of Paclitaxel, Docetaxel, Gemcitabine, Eribulin, Vinorelbine, Capecitabine and Nab-paclitaxel, or as monotherapy. Or cisplatin (Cisplatin) can be chemotherapy. Combination therapy with targeted therapy, including bevacizumab, is permitted, but administration of targeted therapy should be discontinued prior to randomization.
Patients must be able to meet at least one of the following two platinum sensitivity criteria:
(1) Tri-weekly administration 6 times platinum-based chemotherapy or
Weekly platinum-based chemotherapy 18 times
State that has not progressed since (at least stable disease or higher)
(2) Tri-weekly administration of platinum-based chemotherapy 4-6 times or
Weekly dosing (weekly) 12 to 18 times of platinum-based chemotherapy
The state of a complete response or partial response after that.
4) Patients eligible for Germline BRCA1/2 mutation testing, or patients with previously known Germline BRCA1/2 mutation status.
5) Patients who agreed to consent prior to the clinical trial procedure
6) Patients with measurable lesions and/or non-measurable lesions, or no evidence of disease, based on RECIST1.1 on CT performed at baseline prior to randomization.
7) Patients who previously received platinum-based chemotherapy as a potential curative treatment for other cancers (e.g., ovarian cancer) or who received platinum-based chemotherapy as an adjunct chemotherapy/advanced chemotherapy for breast cancer In this case, a period of at least 12 months should elapse between the last administration of curative platinum-based chemotherapy and the start of platinum-based chemotherapy for recurrent, metastatic, or unresectable breast cancer
8) ECOG performance status 0 or 1 point
9) Adequate organ function within 14 days of randomization
A. Absolute Neutrophil Count (ANC) = 1000 cells / mm3
B. Platelets = 100,000/mm3
C. Hemoglobin = 9.0g/dL without blood transfusion (red blood cells) for the previous 7 days
D. Bilirubin = 2.0 x ULN
E. AST (SGOT) = 3 x ULN (5.0 x ULN in case of liver metastasis)
F. ALT (SGPT) = 3 x ULN (5.0 x ULN if liver metastasis is present)
G. Creatinine clearance = 30 mL/min or serum creatinine = 1.5 ULN calculated using Cockcroft-Gault equation
10) 12-lead electrocardiogram (ECG) results for normal or non-clinically significant changes that do not require
1) Patients with tumor progression between the initiation of platinum-based chemotherapy and the time of randomization for recurrent, metastatic, or unresectable triple-negative breast cancer.
2) Severe heart disease (eg, uncontrolled high blood pressure, congestive heart failure [NYHA grade 2 or higher], ventricular arrhythmia, active ischemic heart disease, history of myocardial infarction over the past year)
3) Currently active liver or biliary tract disease (Gilbert syndrome, asymptomatic gallstones, liver metastasis, or stable chronic liver disease can be excluded at the discretion of the researcher).
4) Treatment of previous PARP inhibitors including Talazoparib
5) Patients in clinically significant, uncontrolled medical conditions that limit their ability to comply with research procedures, or other medical conditions that put the patient at risk of developing an unacceptable level of toxicity.
6) Patients with symptomatic CNS metastases or CNS metastases requiring local treatment (eg radiation therapy or surgery). Patients previously treated for brain metastases must be clinically and radiologically stable (after 4 weeks after treatment and until study enrollment, there is no evidence of disease progression and all neurological symptoms have returned to baseline levels. New or imaging) There should be no evidence of advanced brain metastasis) There should be no steroid therapy beyond the physiological dose (> 10 mg prednisolone/day) for at least 2 weeks prior to administration of the clinical study drug. Subjects with limbic carcinoma of the above conditions and related businesses are not allowed.
7) Concurrent use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
8) Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients who have completed curative therapy for HCV are suitable. For patients with evidence of chronic HBV infection, the HBV viral load should be undetectable at the time of enrollment.
9) Patients with a significantly reduced mental state or interfering with the understanding of the study, or whose psychological, familial, sociological, or geographic conditions potentially impede adherence to the study protocol and follow-up schedule.
10) Patients diagnosed with malignant tumors within 5 years. The exceptions are non-melanoma skin cancers treated for curative purposes, in-situ diseases treated for curative purposes, thyroid cancer, or cervical epithelial cancer.
11) Patients unable to swallow orally administered drugs, and patients with gastrointestinal disorders that may interfere with absorption of the study drug.
12) Patients who are pregnant or lactating, or who have a 2-year-old plan during the scheduled clinical trial period from the screening visit to the 7th month after the final administration of the test drug.
13) Previous allogeneic bone marrow transplantation.
14) Patients with known hypersensitivity to talazoparib or to the excipient of the product.
15) Patients who received live vaccine within 30 days prior to the scheduled initial administration of this test drug.
16) Unresolved systemic active infection.
17) Patients with known history of human immunodeficiency virus (HIV) (HIV-1/2 antibody).
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival
- Secondary Outcome Measures
Name Time Method Overall survival;Progression-free survival 2;Objective response rate;Adverse events;Quality of life;Progression-free survival adjusted with presence of visceral metastasis