NeoToc: Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer

Sponsor

Vejle Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02909751

Collaborator

(none)

Enrollment

Location

Arms

28.2

Actual Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	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	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer

Actual Study Start Date :

Sep 14, 2016

Actual Primary Completion Date :

Jan 21, 2019

Actual Study Completion Date :

Jan 21, 2019

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: 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

Drug: Epirubicin 90 mg/m2 iv

Max. 3 months

Drug: Cyclophosphamide 600 mg/m2 iv

Max. 3 months

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

Max. 3 months

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

Max. 3 months.

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

Max. 3 months

Experimental: 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

Drug: Epirubicin 90 mg/m2 iv

Max. 3 months

Drug: Cyclophosphamide 600 mg/m2 iv

Max. 3 months

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

Max. 3 months

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

Max. 3 months.

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

Max. 3 months

Dietary Supplement: Tocotrienol 300 mg x 3 daily

Max. 6 months

Outcome Measures

Primary Outcome Measures

Pathological complete response [26 weeks from date of inclusion]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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