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

Phase 2
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT04496492
Lead Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Brief 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 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.

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
Inclusion Criteria
  • histologically confirmed operable primary breast cancer (T1-T2 N0-1 M0)
  • absence of distant metastasis
  • signed informed consent.
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TocotrienolTocotrienolSubjects receiveTocotrienol 200 mg/twice daily before surgery
Primary Outcome Measures
NameTimeMethod
Changes in blood oxidant capacity4 weeks

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

Changes in blood antioxidant capacity4 weeks

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

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 analysis4 weeks

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

Changes in serum inflammatory cytokines and growth factor4 weeks

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

Absolute and relative changes in peripheral blood mononuclear cells obtained before and after four weeks of tocotrienol treatment, as detected by 13-colors citofluorimetry analysis4 weeks

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

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 analysis4 weeks

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

Secondary Outcome Measures
NameTimeMethod
Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines12,24 and 72 hours

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

Changes in expression of tumor proliferation, hormone receptors and HER24 weeks

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

Trial Locations

Locations (1)

Fondazione IRCCS Istituto Nazionale Tumori

🇮🇹

Milano, Italy

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