Cyclin dEpendent Kinase in tRiple nEGatIVe brEast canceR - a "Window of Opportunity" Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 126
- 试验地点
- 6
- 主要终点
- Early metabolic response
研究概览
简要总结
CAREGIVER is a prospective, randomized, multicenter, open, five-arm study with unequal allocation ratios of 1:1:2:1:2 (palbociclib : paclitaxel : palbociclib + paclitaxel : carboplatin : carboplatin + paclitaxel). Study will be performed in untreated patients with triple-negative breast cancer (TNBC). Potential candidates without previously established diagnosis of TNBC will be included in a Pre-screening Phase, when a biopsy of breast tumor will be taken to confirm the diagnosis of cancer, select patients with TNBC and collect tissue for translational research.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •females or males >18 years old at the time of informed consent signature;
- •diagnosis of potentially resectable or de novo metastatic (stage II-IV) invasive carcinoma of the breast;
- •eligible for standard neoadjuvant or palliative paclitaxel and/or carboplatin-based chemotherapy as determined by Investigator;
- •triple negative tumor defined as:
- •hormone receptor-negative (<1% ER/PgR expression);
- •HER2-negative (Immunohistochemistry (IHC) score ≤1 or IHC score =2 and negative for the amplification by in situ hybridization);
- •multicentric/multifocal disease is allowed, provided that all lesions have been biopsied and their phenotype has been confirmed pathologically as TNBC;
- •no previous anticancer therapy for this malignancy;
- •clinically or radiographically measurable disease (discrete lesion only, enhancement is not included) within the breast, that can be biopsied, defined as longest diameter >2 cm;
- •multicentric or multifocal disease is allowed if at least 1 lesion is >2 cm;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •adequate bone marrow and organ function as defined by the following local laboratory values:
- •hemoglobin ≥9 g/dL;
- •absolute neutrophil count (ANC) ≥1500/μL;
- •platelets ≥100,000/μL;
- •total bilirubin ≤ institutional upper limit of normal (ULN), unless diagnosis of Gilbert syndrome;
- •aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN;
- •creatinine ≤ ULN OR creatinine clearance ≥50 mL/min per Cockcroft-Gault equation for patients with creatinine levels greater than ULN.
- •blood glucose level <120 mg/dL after at least 6 hours of fasting;
- •standard 12-lead electrocardiogram (ECG) without clinically significant abnormalities;
- •ability to undergo contrast-enhanced MRI;
- •ability to swallow and retain oral medication;
- •all study participants of child-bearing potential must agree to use adequate contraceptive methods prior to study entry, during the study and for the following 3 weeks (females) or 14 weeks (males);
- •prior chemotherapy, other targeted anticancer therapies, or prior radiation therapy (outside of treated breast) for other malignancy treated with radical intent is allowed, provided the treatment was completed ≥1 year before informed consent signature;
- •prior bisphosphonate therapy is allowed;
- •willing and able to undergo all the procedures required by the study protocol;
- •provision of written informed consent form prior to receiving any study related procedure.
排除标准
- •inflammatory breast cancer;
- •prior systemic treatment for this malignancy;
- •prior treatment with CDK4/6 inhibitor;
- •known hypersensitivity to study medications or any of their excipients;
- •major surgery or radiotherapy (apart from limited field radiotherapy for symptom control) within 14 days prior to randomization;
- •concurrent invasive malignancy;
- •known HIV, active HBV or HCV infection;
- •active autoimmune disease requiring ongoing immunosuppressive therapy;
- •history of allotransplantation;
- •concurrent treatment with systemic immunosuppressive agents, including steroids, within 3 weeks of enrolment;
- •presence of implants or devices not compatible with MRI;
- •pregnant or nursing female participants;
- •receiving strong inhibitors or inducers of CYP3A4/5 or medications with narrow therapeutic window that are predominantly metabolized through CYP3A4/5;
- •impairment of GI function that may significantly alter the absorption of the oral trial treatments;
- •unwilling or unable to follow protocol requirements, including obligatory biopsies;
- •any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drugs;
- •any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, contraindicate patient participation in the clinical trial or compromise compliance with the protocol.
研究组 & 干预措施
CDK4/6 inhibitor alone: Palbociclib (IMP)
Palbociclib alone (125 mg orally (PO) per day, days 1-14)
干预措施: Palbociclib (Drug)
Chemotherapy alone: Paclitaxel
Paclitaxel alone (80 mg/m^2 intravenously (IV), day 1, 8, 15 and 22)
干预措施: Paclitaxel (Drug)
CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib
Paclitaxel (80 mg/m^2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)
干预措施: Palbociclib (Drug)
CDK4/6 inhibitor + chemotherapy: Paclitaxel + Palbociclib
Paclitaxel (80 mg/m^2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)
干预措施: Paclitaxel (Drug)
Chemotherapy alone: Carboplatin
Carboplatin alone (area under the curve (AUC) 2 IV, day 1, 8, 15 and 22)
干预措施: Carboplatin (Drug)
CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib
Carboplatin (AUC 2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)
干预措施: Palbociclib (Drug)
CDK4/6 inhibitor + chemotherapy: Carboplatin + Palbociclib
Carboplatin (AUC 2 IV, day 1, 8, 15 and 22) + Palbociclib (125 mg PO per day, days 1-21)
干预措施: Carboplatin (Drug)
结局指标
主要结局
Early metabolic response
时间窗: Day 27 (± 3 days)
Difference in early (i.e., after three weeks of therapy, 1 cycle) metabolic response to treatment in chemotherapy-containing arms (chemotherapy ± palbociclib), as assessed by Blinded Central Review comparison of decrease in SUVmax between baseline and Day 27 (± 3 days) 18-fluoro-2-deoxy-d-glucose (18FDG) positron emission tomography - computed tomography (PET-CT). Primary analysis will include comparison between chemotherapy + palbociclib vs chemotherapy alone arms.
次要结局
- Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST)(Day 27 (± 3 days))
- Metabolic tumor volume (MTV) difference(Day 27 (± 3 days))
- Tumor diameter change(Day 27 (± 3 days))
- Change in tumor characteristic(Day 27 (± 3 days))
- SUVmax change(Day 27 (± 3 days))
- Treatment toxicity(Day 27 (± 3 days))