Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Pathological complete response
研究概览
简要总结
The purpose of this study is to investigate whether tocotrienol can improve the effect and reduce the side effects of standard chemotherapy before operation for 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women with histologically verified breast cancer (adenocarcinoma)
- •Age ≥ 18 years.
- •Neoadjuvant treatment indicated according to departmental guidelines
- •PS 0-2 and suited for surgery.
- •Normal heart function, LVEF ≥ 50% by MUGA/ECHO in patients receiving neoadjuvant trastuzumab
- •Normal bone marrow function: Hemoglobin ≥ 6 mmol/l; ANC ≥ 1.5x10^9/l; Thrombocytes ≥ 100x10^9/l.
- •Normal liver function: Bilirubin ≤ 1.5 x upper level of normal, ALAT ≤ 2.5 x upper level of normal, BASP ≤ 2.5 x upper level of normal.
- •Normal kidney function: Creatinine ≤ upper level of normal. In case of increased creatinine, measured/calculated GFR must be ≥ 50 ml/min.
- •Fertile women must present a negative pregnancy test and use a safe contraceptive during and 3 months after the treatment. Intrauterine device without hormone is considered safe.
- •Written and orally informed consent
排除标准
- •Bilateral breast cancer or suspected dissemination. Verified by bilateral mammography, bone scintigraphy, chest and abdomen CT, and PET-CT.
- •Pregnant and breastfeeding women
- •Mental or social conditions that will prevent treatment or follow-up
- •Other simultaneous experimental treatment
- •Immunosuppressive treatment (other than prednisolone during neoadjuvant chemotherapy)
- •Vitamin or nutritional supplements (other than multivitamin tablet and calcium tablet with vitamin D)
- •Active or latent viral/bacterial infection
- •Rheumatoid arthritis or other autoimmune disease
- •Other malignant disease within the past 5 years excl. non-melanoma cancer of the skin and carcinoma in situ cervicis uteri.
- •Previous treatment with docetaxel, paclitaxel, epirubicin, cyclophosphamide, trastuzumab, pertuzumab or tocotrienol
- •Hypersensitivity to any of the active or auxiliary substances
研究组 & 干预措施
Neoadjuvant chemotherapy
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv
干预措施: Epirubicin 90 mg/m2 iv (Drug)
Neoadjuvant chemotherapy
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv
干预措施: Cyclophosphamide 600 mg/m2 iv (Drug)
Neoadjuvant chemotherapy
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv
干预措施: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv (Drug)
Neoadjuvant chemotherapy
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv
干预措施: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only) (Drug)
Neoadjuvant chemotherapy
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv
干预措施: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only) (Drug)
Neoadjuvant chemotherapy + tocotrienol
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
干预措施: Epirubicin 90 mg/m2 iv (Drug)
Neoadjuvant chemotherapy + tocotrienol
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
干预措施: Cyclophosphamide 600 mg/m2 iv (Drug)
Neoadjuvant chemotherapy + tocotrienol
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
干预措施: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv (Drug)
Neoadjuvant chemotherapy + tocotrienol
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
干预措施: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only) (Drug)
Neoadjuvant chemotherapy + tocotrienol
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
干预措施: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only) (Drug)
Neoadjuvant chemotherapy + tocotrienol
HER2 negative:
Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv followed by Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
HER2 positive:
Four cycles of taxane, i.e. 3-weekly docetaxel 100 mg/m2 iv or weekly paclitaxel 80 mg/m2 iv + 3-weekly trastuzumab (8 mg/kg iv saturation, then 6 mg/kg iv) and possibly pertuzumab (840 mg saturation, then 420 mg iv) followed by Four cycles of 3-weekly epirubicin 90 mg/m2 iv and cyclophosphamid 600 mg/m2 iv.
Daily: Tocotrienol 300 mg x 3
干预措施: Tocotrienol 300 mg x 3 daily (Dietary Supplement)
结局指标
主要结局
Pathological complete response
时间窗: 26 weeks from date of inclusion
次要结局
- Correlation of changes in NK-cells with pathological complete response(26 weeks from date of inclusion)
- Correlation of changes in ctDNA with pathological complete response(26 weeks from date of inclusion)
- Number of patients with grade 3-4 side effects(29 weeks from date of inclusion)