A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Paclitaxel in Combination With Reparixin Compared to Paclitaxel Alone as Front-line Therapy for Metastatic Triple- Negative Breast Cancer (FRIDA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 194
- 试验地点
- 66
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The Objectives of this study:
The primary objective of the study was to evaluate 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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occured first) in patients with metastatic triple-negative breast cancer (TNBC) treated with the combination of paclitaxel and orally administered reparixin compared to paclitaxel alone.
The secondary objectives were:
- To determine overall survival (OS).
- To evaluate objective response rates (ORR).
- To determine median PFS (mPFS).
- To assess the safety of the combination of paclitaxel and orally administered reparixin (referred to as combination treatment).
详细描述
The study is a two arm, phase 2 study to evaluate the efficacy of the combination of paclitaxel and reparixin compared to paclitaxel and placebo in metastatic TNBC patients.
In the study two groups There were two groups:
Group 1: paclitaxel 80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle) + reparixin oral tablets 1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21.
Group 2: paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + placebo oral tablets 1200 mg t.i.d. continuing from Day 1 to Day 21.
Study drug (reparixin/placebo) was administered with water prior to the start of the i.v. paclitaxel infusion on Cycle 1, Day 1 and then administered approximately every eight hours (six to ten hours) for 21 consecutive days during each cycle with seven days off-treatment between each cycle. It was preferable that reparixin was taken with food. However, if the patient was unable to eat, study drug was allowed to be administered. When in combination with paclitaxel (Day 1, 8 and 15 of each cycle), reparixin or placebo was administered every approximately eight hours with about 250 mL water and a light meal or snack. Paclitaxel was administered in combination with study drug (reparixin/placebo) as an i.v. infusion on Days 1, 8 and 15 of each 28-day cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female aged ≥ 18 years.
- •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
- •Patients whose metastatic disease is TNBC are eligible even when their primary tumor expressed hormone receptors and/or HER
- •Patients must be newly diagnosed metastatic or must 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
- •Patients with at least one baseline measurable lesion according to RECIST criteria version 1.
- •Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-
- •Life expectancy of at least three months.
- •Patients must be able to swallow and retain oral medication (intact tablet).
- •Able to undergo all screening assessments outlined in the protocol.
- •Adequate organ function (defined by the following parameters):
- •Serum creatinine < 140 μmol/L (< 1.6 mg/dL) or creatinine clearance > 60 mL/min.
- •Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L.
- •Serum bilirubin ≤ 1.5 x upper normal limit (UNL) except patients with Gilbert's syndrome
- •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 UNL in case of liver metastases and ii) ≤ 5 UNL in case of bone metastases; albumin ≥ 2.5 g/dl.
- •No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.
- •No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus-I and -II positive status.
- •Dated and signed IEC/IRB-approved informed consent.
排除标准
- •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.
- •Less than four weeks since last radiotherapy (excluding palliative radiotherapy).
- •Pregnancy or lactation or unwillingness to use adequate method of birth control.
- •Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
- •Active or uncontrolled infection.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function.
- •G>1 pre-existing peripheral neuropathy
- •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
- •Hypersensitivity to:
- •ibuprofen or to more than one non-steroidal anti-inflammatory drug.
- •medications belonging to the class of sulfonamides, with the exception of sulfanilamides (e.g., sulfamethoxazole).
研究组 & 干预措施
paclitaxel+reparixin
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d.
continuing from D 1 to Day 21 of 28-day cycle
干预措施: paclitaxel (Drug)
paclitaxel+reparixin
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d.
continuing from D 1 to Day 21 of 28-day cycle
干预措施: Reparixin (Drug)
paclitaxel+placebo
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle
干预措施: paclitaxel (Drug)
paclitaxel+placebo
paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle
干预措施: placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days
PFS was defined as the number of days between the date of randomization and the date of clinical disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.
次要结局
- Best Overall Response (BOR)(From the start of treatment, every 8 weeks, up to 56 months)
- Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade(Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days)
- Serious AEs and Fatal AEs(Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.)
- Overall Survival (OS)(Baseline until death due to any cause, up to 985 days)
- Objective Response Rate (ORR)(Baseline up to every 8 weeks until documented disease progression, up to 56 months)
- Median Progression-free Survival (mPFS)(At screening and every 8 weeks, up to 721 days)
- Duration of Overall Response (DOR)(Baseline up to every 8 weeks until documented disease progression, up to 557 days)