Iodine Supplementation on Breast Cancer

Effect of Dietary Iodine Supplementation on the Proliferation of Breast Cancer

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).

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Placebo; Drug: iodine; Drug: FEC/TE Placebo; Drug: FEC/TE iodine

Detailed 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).

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carmen Aceves, PhD; Phone Number: 52 442 2381067; Email: caracev@unam.mx

Study Locations

• Mexico
  • Queretaro
    • Querétaro, Queretaro, Mexico, 76001
      • Recruiting
      • Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE
      • Contact: Carlos Avecilla, MD; Phone Number: 442 2154944; Email: drcavecilla@gmail.com
      • Contact: Jose Miguel Torres-Martel, MD; Phone Number: 524422381067; Email: jmiguelmex@hotmail.com
    • Querétaro, Queretaro, Mexico, 76001
      • Recruiting
      • Hospital General Regional #1 IMSS
      • Contact: Joel Rojas, Md; Phone Number: 52 442 216 26 62; Email: joelro_onco@hotmail.com
      • Contact: Guillermo Peralta, MD; Phone Number: 524422381067; Email: drmemop@gmail.com
    • Querétaro City, Queretaro, Mexico, 76000
      • Recruiting
      • Hospital Médico TEC100
      • Contact: Guillermo Peralta Castillo, MD; Phone Number: 524424699698; Email: drmemop@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Early Cancer placebo; The daily supplement of a vegetable colored water solution (drops) for 7 to 35 days in early breast cancer diagnosticated woman. Placebo: vegetable colored water solution (drops). Evaluate the activity of placebo on tumor size, and molecular tumor response, as well as side effects attenuation	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).; Other Names: control
Experimental: Early Cancer Iodine; The daily supplement of an iodine solution (drops, 5 mg/day) for 7 to 35 days in early breast cancer diagnosticated woman	Drug: 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).; Other Names: experimental
Placebo Comparator: Advanced Cancer FEC/TE placebo; The daily supplement of an vegetable colored water solution (drops) within 4 to 6 cycles of chemotherapy with FEC/TE in advanced breast cancer diagnosticated woman. Placebo: vegetable colored water solution (drops). Evaluate the adjuvancy of placebo in FEC/TE treatment on tumor size and molecular tumor response, as well as side effects attenuation.	Drug: 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).
Experimental: Advanced Cancer FEC/TE + Iodine; The daily supplement of an iodine solution (drops, 5 mg/day) within 4 to 6 cycles of chemotherapy with FEC/TE in advanced breast cancer diagnosticated woman Drug: Iodine solution (5 mg/day). Evaluate the adjuvancy of I2 on FEC/TE treatment on tumor size and molecular tumor response, as well as side effects attenuation. Other Name: evaluating the adjuvancy of iodine supplement in FEC/TE treatment	Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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)]
Thyroid Test	Serum quantification of thyroxine, triiodothyronine, and thyroid stimulating hormone (nmol/ml) by ELISA Method	10 minutes (duration of blood withdrawal)
Cardiac damage	Measurement of creatine kinase myocardial band (CK-MB) concentration in serum (ImU/ml) by Colorimetric Method.	10 minutes (duration of blood withdrawal)
Iodine consumes	Measurement of iodine concentration in urine (ug/mL) by Ion Chromatography Method.	10 minutes (duration of urine recollection)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Universidad Nacional Autonoma de Mexico
• Collaborators: Hospital General Regional #1 IMSS, Queretaro México; Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE, Queretaro Mexico; Hospital Medico TEC100, Queretaro México
• Investigators: Principal Investigator: Carmen Aceves, PhD, Universidad Nacional Autonoma de Mexico

Publications and helpful links

General Publications

• Zambrano-Estrada X, Landaverde-Quiroz B, Duenas-Bocanegra AA, De Paz-Campos MA, Hernandez-Alberto G, Solorio-Perusquia B, Trejo-Mandujano M, Perez-Guerrero L, Delgado-Gonzalez E, Anguiano B, Aceves C. Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer. BMC Vet Res. 2018 Mar 12;14(1):87. doi: 10.1186/s12917-018-1411-6.
• Bontempo A, Ugalde-Villanueva B, Delgado-Gonzalez E, Rodriguez AL, Aceves C. Molecular iodine impairs chemoresistance mechanisms, enhances doxorubicin retention and induces downregulation of the CD44+/CD24+ and E-cadherin+/vimentin+ subpopulations in MCF-7 cells resistant to low doses of doxorubicin. Oncol Rep. 2017 Nov;38(5):2867-2876. doi: 10.3892/or.2017.5934. Epub 2017 Sep 1.
• Nava-Villalba M, Nunez-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.
• Alfaro Y, Delgado G, Carabez 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: 10.1186/1476-4598-12-45.
• 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.
• Garcia-Solis P, Alfaro Y, Anguiano B, Delgado G, Guzman RC, Nandi S, Diaz-Munoz M, Vazquez-Martinez 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 prevents cancer promotion. Mol Cell Endocrinol. 2005 May 31;236(1-2):49-57. doi: 10.1016/j.mce.2005.03.001. Epub 2005 Apr 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2005
• Primary Completion (Actual): December 1, 2009
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: September 26, 2018
• First Posted (Actual): September 28, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: September 26, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Trace Elements; Micronutrients; Iodine; Cadexomer iodine
• Other Study ID Numbers: INB-UNAM-004.H; IMSS-HGR1: 185-09-03-05/MPSS (Other Identifier: Hospital General Regional #1 IMSS); ISSSTE 22-205/CEI 248/2009 (Other Identifier: Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data for all primarily and secondary outcome measures will be made available
• IPD Sharing Time Frame: Data will be available within 12 months of study completion
• IPD Sharing Access Criteria: Requestors will be required to sign a data access agreement
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No