High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Event free survival
研究概览
简要总结
This study investigates the effect of high-dose alkylating chemotherapy compared with standard chemotherapy as part of a multimodality treatment approach in patients with oligo-metastatic breast cancer harboring homologous recombination deficiency.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed infiltrating breast cancer
- •Oligometastatic disease defined as one to three distant metastatic lesions, with or without primary tumor, local recurrence, or locoregional lymph node metastases, including the ipsilateral axillary, parasternal, and periclavicular regions. All lesions must be amenable to resection or radiotherapy with curative intent. Staging examinations must have included a PET-CT-scan and a MRI of the liver in case of liver metastases. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as a single lesion. Histologic or cytologic confirmation of at least one distant metastatic lesion is required.
- •No prior line of chemotherapy for metastatic disease (a maximum of 3 months of palliative endocrine therapy is allowed).
- •The tumor must be HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization in case of score 2 or 3 at immunohistochemistry).
- •The tumor is deficient in homologous recombination and/or the patient has a deleterious germline BRCA1 or BRCA2 mutation.
- •At least stable disease of all tumor lesions after three courses of induction chemotherapy
- •Age ≥18 years
- •World Health Organisation (WHO) performance status 0 or 1
- •Adequate bone marrow function (ANC ≥1.0 x 109/l, platelets ≥100 x 109/l)
- •Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal)
- •Adequate renal function (creatinine clearance ≥60 ml/min)
- •If clinically recommended echocardiography, MUGA, or MRI to evaluate if LVEF ≥50%;
- •Signed written informed consent
- •Able to comply with the protocol
排除标准
- •No malignancy other than breast cancer, unless treated with curative intent without the use of chemotherapy or radiation therapy
- •No current pregnancy or breastfeeding. Women of childbearing potential must use adequate contraceptive protection.
- •No concurrent anti-cancer treatment or investigational drugs
研究组 & 干预措施
intensified alkylating chemotherapy
a course chemotherapy with high dose cyclophosphamide, G-CSF and peripheral blood progenitor cell (PBPC) harvest followed by tandem intermediate-dose alkylating therapy (miniCTC, carboplatin 800 mg/m2, thiotepa 240 mg/m2, and cyclophosphamide 3000 mg/m2) with PBPC-reinfusion.
干预措施: carboplatin, thiotepa, and cyclophosphamide (Drug)
three cycles of chemotherapy
three cycles of chemotherapy depending on previously received agents
chemotherapy naïve;three cycles of docetaxel, doxorubicin, and cyclophosphamide previously received anthracyclines without taxanes;three cycles of carboplatin and paclitaxel previously received anthracyclines and taxanes;three cycles of carboplatin and gemcitabine
干预措施: chemotherapy (docetaxel, doxorubicin, cyclofosfamide, carboplatin, paclitaxel, gemcitabine) (Drug)
结局指标
主要结局
Event free survival
时间窗: assessed up to 120 months
time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first
次要结局
- Difference in percentage of patients with grade >2 hematologic toxicity (CTCAE v4.0)(6 months after start of treament)
- Difference in median overall survival(assessed up to 120 months)
- Difference in quality of life (EORTC QLQ-C30 v 3.0)(6 and 12 months post treatment)
- Difference in event free survival(assessed up to 120 months)
- Difference in percentage of patients with grade >2 non-hematologic toxicity (CTCAE v4.0)(6 months after start of treatment)