Study of Reparixin combined with paclitacel compared to paclitaxel alone in patients with metastatic Triple-negative breast cancer
- Conditions
- Metastatic triple negative Breast CancerMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004796-23-CZ
- Lead Sponsor
- Dompé Farmaceutici s.p.a.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 123
1.Female aged > 18 years.
2.Patients with pathologically documented metastatic triple negative breast cancer (TNBC), eligible for treatment with paclitaxel. Paraffin-embedded tissue must be available from metastatic sites, if reasonably accessible, or from the primary tumor, to confirm the diagnosis of TNBC and for correlative studies (only on metastatic tissue). Fifteen slides can be obtained if the full block is not available to be sent or released.
TNBC will be defined as breast cancer with <1% ER+ and <1% PgR+ cells, and HER2 immunohistochemistry score of 0 or 1+ and/or in situ hybridization (ISH) with HER2 gene copy number <4 or a ratio of less than 2 between HER2 gene copy number and centromere of chromosome 17. Patients whose metastatic disease is TNBC are eligible even when their primary tumor expressed hormone receptors and/or HER2.
3.Patients must be newly diagnosed metastatic or have relapsed following a prior (neo)adjuvant chemotherapy regimen. If a taxane (i.e., paclitaxel or docetaxel) was administered as part of the (neo)adjuvant regimen, PD must have occurred > 12 months from the end of previous (neo)adjuvant treatment. For non-taxane (neo)adjuvant regimen, PD must have occurred > 6 months from the end of previous (neo)adjuvant treatment
4.Patients with at least one baseline measurable lesion according to RECIST criteria version 1.1.
5.Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0 1.
6.Life expectancy of at least three months.
7.Patients must be able to swallow and retain oral medication (intact tablet).
8.Able to undergo all screening assessments outlined in the protocol.
9.Adequate organ function (defined by the following parameters):
a)Serum creatinine < 140 µmol/L (< 1.6 mg/dL) or creatinine clearance > 60 mL/min.
b)Serum hemoglobin = 9 g/dL; absolute neutrophil count = 1.5 x 109/L; platelets = 100 x 109/L.
c)Serum bilirubin = 1.5 x upper normal limit (UNL) except patients with Gilbert’s syndrome
d)Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 2.5 x UNL but = 5.0 x UNL in case of liver metastases; alkaline phosphatase (ALP) = UNL but I) = 2.5 x ULN in case of liver metastases and ii) = 5x ULN in case of bone metastases; albumin > 2.5g/dl.
10.No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.
11.No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus I? and II positive status.
12.Dated and signed IEC/IRB-approved informed consent.
13. No history or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Medical Monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 105
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 51
2.Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
3.Less than four weeks since last radiotherapy (excluding palliative radiotherapy).
4.Pregnancy or lactation or unwillingness to use adequate method of birth control.
5.Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
6.Active or uncontrolled infection.
7.Malabsorption syndrome, disease significantly affecting gastrointestinal function.
8.G>1 pre-existing peripheral neuropathy
9.Any other invasive malignancy from which the patient has been disease-free for less than 5 years with the exception of curatively treated basal or squamous cell skin cancer
10.Hypersensitivity to:
a)paclitaxel
b)ibuprofen or to more than one non-steroidal anti-inflammatory drug.
c)more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib; hypersensitivity to sulphanilamide antibiotics alone (e.g.sulfamethoxazole) does not qualify for exclusion.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Progression Free Survival (PFS) defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according RECIST criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occurs first. ;Secondary Objective: To determine the median PFS (mPFS) <br>To determine Overall Survival (OS).<br>To evaluate Objective Response Rates (ORR)<br>To assess the safety of the combination of paclitaxel and orally administered reparixin.<br>;Timepoint(s) of evaluation of this end point: at disease progression or death whichever occurs before;Primary end point(s): Progression Free Survival (PFS) defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1)median PFS (mPFS)defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to RECIST criteria version 1.1, or death for any cause, whichever occurs first <br>2)overall Survival defined as the interval (days) between randomization and death from any cause.<br>3)objective response rates (ORR) defined as the percentage of the patients reaching complete remission (CR), partial remission (PR) or stable disease (SD) according to RECIST criteria version 1.1.<br>•CR rate<br>•PR rate<br>•SD rate<br>•PD rate<br>4)safety of the combination treatment<br>;Timepoint(s) of evaluation of this end point: 1) at disease progression or death<br>2) death<br>3) every eight weeks until disease progresion or death wichever occurs first<br>4) throughout the study