TOCANNATO: Preoperative Use of Tocotrienol From Annatto Bixa Orellana L. in Breast Cancer Patients: a Prospective Clinical Trial.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
An open-label, single center, phase 2 prospective observational clinical study
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tocotrienol Subjects receiveTocotrienol 200 mg/twice daily before surgery |
Drug: Tocotrienol
Tocotrienol 200 mg orally twice a day
|
Outcome Measures
Primary Outcome Measures
- Changes in blood oxidant capacity [4 weeks]
Oxidant capacity (through tock fast-Li Starfish) (µmol/L) was measured in patients' serum samples.
- Changes in blood antioxidant capacity [4 weeks]
Antioxidant capacity (through TAC Track, Li Starfish) (µmol/L) was 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 analysis [4 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 analysis [4 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
- 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 [4 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 factor [4 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
Secondary Outcome Measures
- Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines [12,24 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 HER2 [4 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
histologically confirmed operable primary breast cancer (T1-T2 N0-1 M0)
-
absence of distant metastasis
-
signed informed consent.
Exclusion Criteria:
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Previous malignancies other than in situ cervical carcinoma or nonmelanoma skin cancer
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Breast cancer recurrence
-
Metastatic breast cancer
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Non-epithelial breast cancer at histological examination
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In situ lobular breast cancer
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Participation in other randomized clinical trials that could interfere with current study
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Living distant from center and unable to attend for check-ups and meetings
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fondazione IRCCS Istituto Nazionale Tumori | Milano | Italy | 20133 |
Sponsors and Collaborators
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
- Principal Investigator: Cristina Ferraris, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2014-005275-92