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Breast CancerPhase 2TOCANNATONCT04496492

Preoperative Use of Tocotrienol From Annatto Bixa Orellana L. in Breast Cancer Patients: a Prospective Clinical Trial.

A Phase 2 study testing Tocotrienol in people with Breast Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Tocotrienols have shown strong in vitro and in vivo anti-oxidant and anticancer activity, promoting apoptosis and regulating oncogenic targets in breast cancer. However their clinical use is still experimental especially in preoperative setting, where there are still no data of antioxidant and antiinflammatory… Read more about this study

Who is it for?
Ages 30 to 65 years
Conditions the study is for
Breast Cancer
What is being tested?
Tocotrienol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteItaly
Study dates
9 Feb 2016to 6 Jul 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • histologically confirmed operable primary breast cancer (T1-T2 N0-1 M0)
  • absence of distant metastasis
  • signed informed consent.

Who cannot join

  • Previous malignancies other than in situ cervical carcinoma or nonmelanoma skin cancer
  • Breast cancer recurrence
  • Metastatic breast cancer
  • Non-epithelial breast cancer at histological examination
  • In situ lobular breast cancer
  • Participation in other randomized clinical trials that could interfere with current study
  • Living distant from center and unable to attend for check-ups and meetings

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Fondazione IRCCS Istituto Nazionale Tumori

    Milan, 20133

Other trials in Italy

About this study

Official title: Preoperative Use of Tocotrienol Associated With Personalized Nutritional and Psychoeducational Support in Women With Primary Breast Cancer.

Tocotrienols have shown strong in vitro and in vivo anti-oxidant and anticancer activity, promoting apoptosis and regulating oncogenic targets in breast cancer. However their clinical use is still experimental especially in preoperative setting, where there are still no data of antioxidant and antiinflammatory beneficial roles. This study is a prospective observational clinical study enrolling 50 patients with primary breast cancer (T1-2, N0-1, M0) who received 4-weeks oral treatment of delta-T3 before surgery (200 mg/twice daily) with personalized nutritional and psychoeducational support. This study evaluates the effects of treatment on oxidant (tock fast-Li Starfish) and antioxidant capacity (TAC Track, Li Starfish), anti-inflammatory activity (complete profiling of adaptive and innate cell immunity, immunologic serum markers (miRNA)), immunological response on tumor (gene expression profiling on preoperative tissue tumor biopsy and on surgical specimen), TNF-alpha, IL-6 and VEGF and proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines.

This study evaluates the effects of treatment on oxidant (tock fast-Li Starfish) and antioxidant capacity (TAC Track, Li Starfish), on anti-inflammatory activity (complete profiling of adaptive and innate cell immunity, immunologic serum markers (miRNA)), on immunological response on tumor (gene expression profiling on preoperative tissue tumor biopsy and on surgical specimen), on TNF-alpha, IL-6 and VEGF, on proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines.

Read the detailed description

An open-label, single center, phase 2 prospective observational clinical study

Conditions
Breast Cancer
Being tested
Tocotrienol
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TocotrienolDrug

    Tocotrienol 200 mg orally twice a day

Study groups in NCT04496492
Study groupRoleWhat they receive
TocotrienolExperimentalSubjects receiveTocotrienol 200 mg/twice daily before surgery
Receives: Drug: Tocotrienol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in blood oxidant capacity

    Oxidant capacity (through tock fast-Li Starfish) (µmol/L) was measured in patients' serum samples.

    Measured: 4 weeks

  2. Changes in blood antioxidant capacity

    Antioxidant capacity (through TAC Track, Li Starfish) (µmol/L) was measured in patients' serum samples.

    Measured: 4 weeks

  3. Absolute and relative changes in peripheral blood mononuclear cells obtained before and after four weeks of tocotrienol treatment, as detected by 13-colors citofluorimetry analysis

    Peripheral blood mononuclear cells were measured by 13-color cytofluorimetry analysis in patients' serum samples.

    Measured: 4 weeks

  4. Changes of immune-related miRNA levels in patients' serum samples obtained before and after four weeks of tocotrienol treatment, as determined by quantitative real-time PCR analysis

    Immune-related miRNA levels were determined by quantitative real-time PCR analysis in patients' serum samples obtained before and after four weeks of tocotrienol treatment

    Measured: 4 weeks

  5. Changes in immune response associated gene levels in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment, respectively, as determined by gene expression profiling analysis

    Immune response associated gene levels were determined by gene expression profiling analysis in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment

    Measured: 4 weeks

  6. Changes in serum inflammatory cytokines and growth factor

    Blood inflammatory cytokines and growth factor (through TNF-alpha (pg/ml), IL-6 (pg/ml) and VEGF (pg/ml) quantifications) were measured in patients' serum samples

    Measured: 4 weeks

Secondary outcomes (2)

  1. Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines

    Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines was measured through cell culture analysis.

    Measured: 12,24 and 72 hours

  2. Changes in expression of tumor proliferation, hormone receptors and HER2

    Expression of tumor proliferation index (Ki67), estrogen and/progesterone receptor and HER2 oncoprotein by IHC was determined in preoperative tumor biopsies and in surgical specimens

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2020
  2. Study start9 Feb 2016
  3. Primary completion9 Feb 2016
  4. Study completion6 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04496492
Sponsor's protocol ID
2014-005275-92
Other IDs
2014
Acronym
TOCANNATO
Status last verified
Jun 2020
First submitted
26 Jun 2020
Last updated
3 Aug 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Qureshi AA, Pearce BC, Nor RM, Gapor A, Peterson DM, Elson CE. Dietary alpha-tocopherol attenuates the impact of gamma-tocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J Nutr. 1996 Feb;126(2):389-94. doi: 10.1093/jn/126.2.389.

    PubMed 8632210

  • Rasool AH, Rahman AR, Yuen KH, Wong AR. Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res. 2008 Sep;31(9):1212-7. doi: 10.1007/s12272-001-1291-5. Epub 2008 Sep 20.

    PubMed 18806966

  • Song BL, DeBose-Boyd RA. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. J Biol Chem. 2006 Sep 1;281(35):25054-61. doi: 10.1074/jbc.M605575200. Epub 2006 Jul 10.

    PubMed 16831864

  • Pearce BC, Parker RA, Deason ME, Qureshi AA, Wright JJ. Hypocholesterolemic activity of synthetic and natural tocotrienols. J Med Chem. 1992 Oct 2;35(20):3595-606. doi: 10.1021/jm00098a002.

    PubMed 1433170

  • Begum AN, Terao J. Protective effect of alpha-tocotrienol against free radical-induced impairment of erythrocyte deformability. Biosci Biotechnol Biochem. 2002 Feb;66(2):398-403. doi: 10.1271/bbb.66.398.

    PubMed 11999415

  • Palozza P, Verdecchia S, Avanzi L, Vertuani S, Serini S, Iannone A, Manfredini S. Comparative antioxidant activity of tocotrienols and the novel chromanyl-polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells. Mol Cell Biochem. 2006 Jul;287(1-2):21-32. doi: 10.1007/s11010-005-9020-7. Epub 2006 Apr 28.

    PubMed 16645729

  • Packer L, Weber SU, Rimbach G. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr. 2001 Feb;131(2):369S-73S. doi: 10.1093/jn/131.2.369S.

    PubMed 11160563

  • Houston MC, Fazio S, Chilton FH, Wise DE, Jones KB, Barringer TA, Bramlet DA. Nonpharmacologic treatment of dyslipidemia. Prog Cardiovasc Dis. 2009 Sep-Oct;52(2):61-94. doi: 10.1016/j.pcad.2009.02.002. No abstract available.

    PubMed 19732602

  • Zaiden N, Yap WN, Ong S, Xu CH, Teo VH, Chang CP, Zhang XW, Nesaretnam K, Shiba S, Yap YL. Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion. J Atheroscler Thromb. 2010 Oct 27;17(10):1019-32. doi: 10.5551/jat.4911. Epub 2010 Aug 10.

    PubMed 20702976

  • Qureshi AA, Sami SA, Salser WA, Khan FA. Synergistic effect of tocotrienol-rich fraction (TRF(25)) of rice bran and lovastatin on lipid parameters in hypercholesterolemic humans. J Nutr Biochem. 2001 Jun;12(6):318-329. doi: 10.1016/s0955-2863(01)00144-9.

    PubMed 11516635

  • Qureshi AA, Sami SA, Salser WA, Khan FA. Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans. Atherosclerosis. 2002 Mar;161(1):199-207. doi: 10.1016/s0021-9150(01)00619-0.

    PubMed 11882333

  • Qureshi AA, Sami SA, Khan FA. Effects of stabilized rice bran, its soluble and fiber fractions on blood glucose levels and serum lipid parameters in humans with diabetes mellitus Types I and II. J Nutr Biochem. 2002 Mar;13(3):175-187. doi: 10.1016/s0955-2863(01)00211-x.

    PubMed 11893482

  • Montonen J, Knekt P, Jarvinen R, Reunanen A. Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care. 2004 Feb;27(2):362-6. doi: 10.2337/diacare.27.2.362.

    PubMed 14747214

  • Baliarsingh S, Beg ZH, Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis. 2005 Oct;182(2):367-74. doi: 10.1016/j.atherosclerosis.2005.02.020. Epub 2005 Apr 20.

    PubMed 16159610

  • Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care. 2005 Nov;28(11):2745-9. doi: 10.2337/diacare.28.11.2745.

    PubMed 16249550

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tocotrienol in people with Breast Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in blood oxidant capacity (time frame: 4 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04496492, which also lists 74 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.

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