Iodine Supplementation on Breast Cancer

Breast Cancer Clinical Trial

Official title:

Effect of Dietary Iodine Supplementation on the Proliferation of Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03688958
• Other study ID #: INB-UNAM-004.H
• Secondary ID: IMSS-HGR1: 185-0
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2005
• Est. completion date: June 2020

Study information

• Verified date: September 2018
• Source: Universidad Nacional Autonoma de Mexico
• Contact: Carmen Aceves, PhD
• Phone: 52 442 2381067
• Email: caracev[@]unam.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial investigates the effect of oral supplement of molecular iodine (I2) alone and in combination with 4 to 6 cycles of FEC/TE (5-fluorouracil, epirubicin, cyclophosphamide/taxotere, epirubicin) treatment in woman diagnosticated with early (stage II) and advance (stage III) breast cancer, respectively. The study analyzes the clinical response [tumor size, thyroid status, side effects (Common Toxicity Criteria V4.0)] and molecular mechanisms in the tumor samples (transcriptomic, proteins and immune responses).

Description:

The leading causes of failure of breast cancer treatment are the rapid development of metastases and tumor resistance to antineoplastic drugs. Anthracyclines (doxorubicin (DOX), epirubicin, etc.) are the golden standard in neoadjuvant therapy and are commonly used in the FEC/TE (5-fluorouracil, epirubicin, cyclophosphamide/taxotere, epirubicin) combination therapy during advanced breast cancer. However, even when treated with this potent chemotherapeutic combination, 30% of patients develop chemoresistance and cardiomyopathic side effects. Previous studies support that the oral supplement of molecular iodine (I2) exerts synergistic antineoplastic and cardioprotective impact when used in combination with the DOX in rodent and canine mammary cancer model. The present study performed two randomized clinical groups including women with early (stage II) and advanced (stage III) breast cancer. In the Early group, women were treated with I2 (5 mg/day) or placebo (colored water) for 7 to 35 days. In the Advanced group, patients received treatment (I2 or placebo) along with 4 to 6 cycles of FEC/TE treatment. The study analyzes the clinical response [tumor size, thyroid status, side effects (Common Toxicity Criteria V4.0)] and molecular mechanisms in the tumor samples (transcriptomic, proteins and immune responses).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 2020
• Est. primary completion date: December 1, 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 81 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed, stage II or III breast cancer

• Scheduled to surgical of the primary tumor (stage II)

• Will receive neoadjuvant FEC/TE chemotherapy (stage III).

• age > 18 and < 81 years

• Non-pregnant

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Known sensitivity to iodine or FEC/TE

• Concurrent severe and/or uncontrolled disease

• Myocardial infarction within the last six months before the study

• Unstable or uncontrolled hypertension

• Thyroid dysfunction

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Placebo
Selected patients with early breast cancer (stage II) non-pretreated received colored water solution (placebo) within the time before the hospital assigned them to her surgery (7 to 35 days).
• iodine
Selected patients with early breast cancer (stage II) non-pretreated received iodine solution (Experimental) within the time before the hospital assigned them to her surgery (7 to 35 days).
• FEC/TE Placebo
The selected patients with advanced breast cancer (stage III) non-pretreated received colored water solution (placebo) within the time of oncology designed chemotherapy treatment FEC/TE (4 or 6 cycles/ every 21 days).
• FEC/TE iodine
The selected patients with advanced breast cancer (stage III) non-pretreated received iodine solution (experimental) within the time of oncology designed chemotherapy treatment (4 or 6 cycles/ every 21 days).

Locations

Country	Name	City	State
Mexico	Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE	Querétaro	Queretaro
Mexico	Hospital General Regional #1 IMSS	Querétaro	Queretaro
Mexico	Hospital Médico TEC100	Querétaro City	Queretaro

Sponsors (4)

Lead Sponsor	Collaborator
Universidad Nacional Autonoma de Mexico	Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE, Queretaro Mexico, Hospital General Regional #1 IMSS, Queretaro México, Hospital Medico TEC100, Queretaro México

Country where clinical trial is conducted

Mexico, 

References & Publications (6)

Aceves C, Anguiano B, Delgado G. The extrathyronine actions of iodine as antioxidant, apoptotic, and differentiation factor in various tissues. Thyroid. 2013 Aug;23(8):938-46. doi: 10.1089/thy.2012.0579. Review. — View Citation

Alfaro Y, Delgado G, Cárabez A, Anguiano B, Aceves C. Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection. Mol Cancer. 2013 May 24;12:45. doi: 10.1186/1476-459 — View Citation

Bontempo A, Ugalde-Villanueva B, Delgado-González E, Rodríguez ÁL, Aceves C. Molecular iodine impairs chemoresistance mechanisms, enhances doxorubicin retention and induces downregulation of the CD44+/CD24+ and E-cadherin+/vimentin+ subpopulations in MCF- — View Citation

García-Solís P, Alfaro Y, Anguiano B, Delgado G, Guzman RC, Nandi S, Díaz-Muñoz M, Vázquez-Martínez O, Aceves C. Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I-) treatment Evidence that I2 — View Citation

Nava-Villalba M, Nuñez-Anita RE, Bontempo A, Aceves C. Activation of peroxisome proliferator-activated receptor gamma is crucial for antitumoral effects of 6-iodolactone. Mol Cancer. 2015 Sep 17;14:168. doi: 10.1186/s12943-015-0436-8. — View Citation

Zambrano-Estrada X, Landaverde-Quiroz B, Dueñas-Bocanegra AA, De Paz-Campos MA, Hernández-Alberto G, Solorio-Perusquia B, Trejo-Mandujano M, Pérez-Guerrero L, Delgado-González E, Anguiano B, Aceves C. Molecular iodine/doxorubicin neoadjuvant treatment imp — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response [change in size]	The size of the tumor is calculated by measuring the largest diameter of the tumor in the axial plane. The first measurement is obtained in the mammography taken before the start of the protocol and the second measurement is made on the tissue after surgery. The change percentage is obtained by dividing the final size between the initial size by 100.	20 minutes
Primary	Incidence of treatment-emergent adverse events [Safety and Tolerability]).	Presence or not of: Edema, hand-foot syndrome, anorexia, vomiting, diarrhea, nausea, asthenia (patient interview and clinical auscultation)	40 minutes
Primary	Differential Blood Count	Differential blood count gives relative percentage of each type of white blood cell and helps reveal abnormal white blood cell populations (eg, blasts, immature granulocytes, or circulating mature cells in the peripheral blood).	10 minutes (duration of blood withdrawal)]
Primary	Thyroid Test	Serum quantification of thyroxine, triiodothyronine, and thyroid stimulating hormone (nmol/ml) by ELISA Method	10 minutes (duration of blood withdrawal)
Primary	Cardiac damage	Measurement of creatine kinase myocardial band (CK-MB) concentration in serum (ImU/ml) by Colorimetric Method.	10 minutes (duration of blood withdrawal)
Primary	Iodine consumes	Measurement of iodine concentration in urine (ug/mL) by Ion Chromatography Method.	10 minutes (duration of urine recollection)
Primary	Tumor classification type and modification after treatment	Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) presence in biopsy (initial) and tumor sample after treatments (final) by immunohistochemical method (number of positive cells/field).	40 minutes
Secondary	Disease-free survival	The follow-up of the disease-free survival (DFS) at 5 years. (patient interview and clinical auscultation each six months)	Every 6 months for 5 years