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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Vejle, Denmark
    • Vejle Hospital, Department of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Vejle Hospital
• Investigators: Study Chair: Erik H Jakobsen, MD, Vejle Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2016
• Primary Completion (Actual): January 21, 2019
• Study Completion (Actual): January 21, 2019

Study Registration Dates

• First Submitted: September 16, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimate): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Micronutrients; Antibiotics, Antineoplastic; Vitamins; Antioxidants; Docetaxel; Cyclophosphamide; Trastuzumab; Epirubicin; Vitamin E; Tocopherols; Tocotrienols; Pertuzumab
• Other Study ID Numbers: NeoToc