Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer (NeoToc)

Vejle Hospital

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02909751

NeoToc

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Neoadjuvant chemotherapy

Active Comparator group

Description:

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

Treatment:

Drug: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only)

Drug: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv

Drug: Cyclophosphamide 600 mg/m2 iv

Drug: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only)

Drug: Epirubicin 90 mg/m2 iv

Neoadjuvant chemotherapy + tocotrienol

Experimental group

Description:

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

Treatment:

Dietary Supplement: Tocotrienol 300 mg x 3 daily

Drug: Pertuzumab 840 mg iv saturation, then 420 mg iv (selected HER2 positive patients only)

Drug: Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv

Drug: Cyclophosphamide 600 mg/m2 iv

Drug: Trastuzumab 8 mg/kg iv saturation, then 6 mg/kg iv (HER2 positive patients only)

Drug: Epirubicin 90 mg/m2 iv