Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Epirubicin 90 mg/m2 iv
* Drug: Cyclophosphamide 600 mg/m2 iv
* Drug: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv
* Drug: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only)
* Drug: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only)
* Dietary Supplement: Tocotrienol 300 mg x 3 daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Neoadjuvant chemotherapy<br>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 | Drug: Epirubicin 90 mg/m2 iv<br>* Max. 3 months<br>Drug: Cyclophosphamide 600 mg/m2 iv<br>* Max. 3 months<br>Drug: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv<br>* Max. 3 months<br>Drug: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only)<br>* Max. 3 months.<br>Drug: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only)<br>* Max. 3 months<br>|
| Experimental: Neoadjuvant chemotherapy + tocotrienol<br>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 | Drug: Epirubicin 90 mg/m2 iv<br>* Max. 3 months<br>Drug: Cyclophosphamide 600 mg/m2 iv<br>* Max. 3 months<br>Drug: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv<br>* Max. 3 months<br>Drug: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only)<br>* Max. 3 months.<br>Drug: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only)<br>* Max. 3 months<br>Dietary Supplement: Tocotrienol 300 mg x 3 daily<br>* Max. 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response |  | 26 weeks from date of inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |