Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer

NCT02909751 | Completed Phase 2

• 1 other identifier: NeoToc
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  26 weeks from date of inclusion

Secondary Outcomes (3)

• 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

Study Arms (2)

Neoadjuvant chemotherapy

ACTIVE COMPARATOR

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; 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)

Neoadjuvant chemotherapy + tocotrienol

EXPERIMENTAL

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; 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

Interventions

Epirubicin 90 mg/m2 iv DRUG

Max. 3 months

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy + tocotrienol

Cyclophosphamide 600 mg/m2 iv DRUG

Max. 3 months

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy + tocotrienol

Docetaxel 100 mg/m2 iv OR paclitaxel 80 mg/m2 iv DRUG

Max. 3 months

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy + tocotrienol

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

Max. 3 months.

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy + tocotrienol

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

Max. 3 months

Neoadjuvant chemotherapy; Neoadjuvant chemotherapy + tocotrienol

Tocotrienol 300 mg x 3 daily DIETARY_SUPPLEMENT

Max. 6 months

Neoadjuvant chemotherapy + tocotrienol

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vejle Hospital: lead

Study Sites (1)

Vejle hospital, Department of Oncology

Vejle, Denmark

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin; Cyclophosphamide; Docetaxel; Paclitaxel; Trastuzumab; pertuzumab; Tocotrienols

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Erik H Jakobsen, MD

  Vejle Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 21, 2016
• Study Start: September 14, 2016
• Primary Completion: January 21, 2019
• Study Completion: January 21, 2019
• Last Updated: May 20, 2021

Record last verified: 2021-05

Locations

DK (1)