A Phase II Study of Neoadjuvant Carboplatin/Paclitaxel Followed by Dose-Dense Doxorubicin/Cyclophosphamide in Patients With Hormone Receptor Negative, HER2 Receptor Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 6
- 主要终点
- Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate
研究概览
简要总结
This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in subjects with triple-negative breast cancer in neoadjuvant settings.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have histologically or cytologically confirmed invasive breast cancer which meets the following criteria:
- •Estrogen Receptor (ER) and Progesterone Receptor (PR)-negative as defined by local standard clinical immunohistochemistry (IHC) < 1%.
- •HER2-negative using local standard testing. Negative is defined as IHC 0 or 1+ (if 2+, must reflex to ISH method). If ISH method is used, ratio < 2 is considered negative.
- •Clinical tumor size of at least 2.1 cm (T2) by palpation or imaging, regardless of the ipsilateral regional lymph node status, or any tumor size but with ipsilateral regional lymph nodes involved by the tumor (any T if ipsilateral regional node positive). Subjects with inflammatory breast cancer are eligible. If bilateral breast cancer is present, the subject is eligible if the contralateral tumor is DCIS only (without any invasive disease on biopsy) or another invasive breast cancer of any size that is also ER, PR and HER2 negative.
- •Any radiographic abnormal ipsilateral regional lymph nodes or any clinically concerning ipsilateral regional lymph nodes with the exception of internal mammary nodes should be sampled with percutaneous biopsy, but no sentinel axillary lymph node mapping/biopsy is allowed before chemotherapy. If clinically node negative (cNO), pre-chemotherapy ipsilateral sentinel axillary lymph node mapping/biopsy is not allowed.
- •Candidate for neoadjuvant chemotherapy.
- •Age > 18 years and < 75 years
- •ECOG Performance Status <
- •Left ventricular ejection fraction (LVEF) ≥ LLN (per institutional normal) determined by
- •Adequate organ and marrow function as determined by study protocol
- •Non Pregnant. Women of childbearing potential must have a negative pregnancy test (HCG serum or urine) within 30 days prior to study registration and to be repeated if not done within 7 days of starting chemotherapy.
- •Female subjects must meet one of the following:
- •Natural postmenopausal before the screening visit defined as no menses at any time in the preceding 12 consecutive months, or
- •Prior bilateral oophorectomy or bilateral tubal ligation, or
- •If they are of childbearing potential, agree to practice two effective methods of contraception per discussion with the treating physicians from
- •Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to one of the following:
- •Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, or
- •Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
- •Ability to understand a written informed consent document, and the willingness to sign it.
排除标准
- •Prior chemotherapy or radiation therapy for invasive breast cancer within 6 months before registration.
- •Prior investigational drugs or interventions for invasive breast cancer within 6 months before registration are not allowed. Prior participation in window-of-opportunity trials without therapeutic intent is allowed if intervention is no more than 3 weeks duration.
- •Stage IV metastatic breast cancer
- •History of allergic reactions attributed to compounds of similar chemical composition to chemotherapy to be used in this study.
- •Breastfeeding women. Cytotoxic chemotherapy is drug with the potential for teratogenic or abortifacient effects. Due to unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cytotoxic chemotherapy, breastfeeding should be discontinued.
- •Baseline peripheral neuropathy of severity > grade 1
- •Other invasive cancer diagnosis within the past 5 years other than non-melanoma skin cancer.
- •Prior axillary lymph node dissection that preclude patient from surgical evaluation of axillary lymph node status.
研究组 & 干预措施
Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
干预措施: Carboplatin (Drug)
Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
干预措施: Paclitaxel (Drug)
Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
干预措施: Doxorubicin (Drug)
Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
干预措施: Cyclophosphamide (Drug)
Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
干预措施: Pegfilgrastim (Drug)
Neoadjuvant Chemotherapy
Regimen A (cycles 1-4):
Paclitaxel 80 mg/m2; administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks) Carboplatin AUC=2 (dose calculation by determining creatine clearance with Cockroft Gault using adjusted body weight); administer intravenously on day 1, 8, 15 of cycles 1, 2, 3, 4 (every 3 weeks)
Regimen B (cycles 5-8):
Doxorubicin 60 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Cyclophosphamide 600 mg/m2; administer intravenously on day 1 of cycles 5, 6, 7, 8 (every 2 weeks) Pegfilgrastim (for use on Doxorubicin/Cyclophosphamide cycles only), filgrastim, or biosimilar support on day 2 - 3 of cycles 5, 6, 7, 8 (every 2 weeks)
There is a one week break between the end of cycle 4 and the beginning of cycle 5.
Regimen C:
Surgical intervention for management of breast cancer diagnosis; procedure and timing as determined by surgical team.
干预措施: Filgrastim (Drug)
结局指标
主要结局
Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate
时间窗: Up to 2 years
pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders.
次要结局
- Number of Cycles of Chemotherapy Administered(Week 12 to week 18 to account for possible delays)
- Number of Treatment-related Toxicities Experienced by Participants(Up to week 12)
- Recurrence-free Survival (RFS)(Up to 2 years)
- Total Dose of Chemotherapy Administered(Week 12 to week 18 to account for possible delays)
- Delays of Administered Chemotherapy(Week 12 to week 18 to account for possible delays)
- Overall Survival (OS)(Up to 2 years)