GUided Treatment Based on Mini-PDX in metastaTIc refractOry Triple Negative Breast Cancer(GUMPTION)：a Prospective Randomized Controlled Single Center Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
Triple-negative breast cancer constitutes 15-20% of cases of breast cancer and is defined by the absence of estrogen receptors, progesterone receptors, and overexpression or gene amplification of HER2. Although the addition of immune checkpoint inhibitors could improve the outcome of patients with metastatic triple-negative breast cancer (mTNBC), chemotherapy has been the standard of care for systemic treatment for patients with mTNBC. Prognoses remain poor, with reported median overall survival estimates of approximately 18 months or less with available treatments. A meta-analysis of seven clinical trials showed that the median objective response rate (ORR) of second or later line of chemotherapy in mTNBC was only 11%.
Patient-derived xenograft (PDX) tumor model, which preserves the histologic and genetic characteristics of patients' tumors, has shown its predictive value of clinical outcomes and are used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. However, long time period and low success rate has limited its application in clinical practice.
Mini patient derived xenograft (miniPDX) offers an effective alternative as it only takes about 7 days for drug sensitivity test and could thus provide guidance for prompt personalized treatment for each patient.
Thus, the investigators conduct this single-center, prospective, randomized controlled clinical study to investigate the efficacy of guided treatment based on Mini-PDX in patients with metastatic refractory triple negative breast cancer.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-70 years;
- •an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Estimated lifetime is ≥ 3 months;
- •Histopathologically confirmed recurrent (unresectable) or metastatic triple-negative breast cancer; ER and PR negative is defined as ER <1% positive, PR <1% positive. HER-2 negative is defined as HER-2 (-) or (1+) by immunohistochemistry, HER-2 (2+) must be tested by FISH with negative result, HER-2 (1+) (1+), FISH is optional and negative;
- •Have at least one measurable target lesion according to RECIST 1.1 criteria;
- •Biopsy of the tumor lesion and the specimen passes laboratory quality control;
- •A minimum of 2 prior cytotoxic chemotherapy regimens (including at least one line of platinum-containing regimen) in metastatic settings are required prior to enrollment in this trial;
- •Adequate organ function, i.e. meeting the following criteria.
- •Hb ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 109 /L; PLT ≥ 75 × 109 /L.
- •Liver function: total bilirubin TBIL ≤ 1.5×ULN (upper limit of normal); ALT and AST ≤ 3×ULN.
- •serum Cr ≤ 1.5×ULN.
- •Subjects voluntarily joined the study, signed the informed consent form, were compliant and cooperated with the follow-up.
排除标准
- •1）Pregnancy or lactation；
- •2）History of autoimmune disease；
- •3）Anticancer- and radiation therapy-related toxicities have not resolved or downgraded to Grade 1 or less;
- •Symptomatic central nervous system (CNS) disease;
- •Previous treatment of Immune checkpoint inhibitors;
- •History of other malignancies within the past five years, with the exception of cured non-malignant melanoma of the skin and carcinoma in situ of the cervix.
研究组 & 干预措施
Personalized treatment guided by Mini-PDX
The tumor tissue is used for drug sensitivity test by Mini-PDX, and acquiring the genetic information by RNA-sequence. Patients with mTNBC will receive personalized treatment guided by the experimental results of mini-PDX and RNA sequencing.
干预措施: Personalized treatment guided by mini-PDX and RNA sequencing (Drug)
Treatment of Physician's Choice (TPC)
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
干预措施: Nab paclitaxel (Drug)
Treatment of Physician's Choice (TPC)
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
干预措施: Eribulin (Drug)
Treatment of Physician's Choice (TPC)
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
干预措施: Vinorelbine (Drug)
Treatment of Physician's Choice (TPC)
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
干预措施: Gemcitabine (Drug)
Treatment of Physician's Choice (TPC)
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Objective response rate
时间窗: Through study completion, an expected average of 1 year
To compare the Objective Response Rate (ORR) of patients who recieve persionalized treatment based on mini-PDX model with ORR of patients who receive Treatment of Physician's Choice (TPC). ORR is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1. ORR will be calculated based on the Investigator assessment of response. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
次要结局
- Adverse events(Through study completion, an expected average of 1 year)
- Overall Survival(Through study completion, an expected average of 1 year)
- Progression-Free Survival(Through study completion, an expected average of 1 year)
研究者
Xichun Hu
Director of Medical Oncology
Fudan University