Clinical trial NCT03688958: Iodine Supplementation on Breast Cancer
Official title: Effect of Dietary Iodine Supplementation on the Proliferation of Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Universidad Nacional Autonoma de Mexico
Sponsor class: OTHER
Collaborators: name: Hospital General Regional #1 IMSS, Queretaro México
name: Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE, Queretaro Mexico
name: Hospital Medico TEC100, Queretaro México
First posted: 2018-09-28
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 81
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: Tumor response [change in size]
timeFrame: 20 minutes
measure: Incidence of treatment-emergent adverse events [Safety and Tolerability]).
timeFrame: 40 minutes
measure: Differential Blood Count
timeFrame: 10 minutes (duration of blood withdrawal)]
measure: Thyroid Test
timeFrame: 10 minutes (duration of blood withdrawal)
measure: Cardiac damage
timeFrame: 10 minutes (duration of blood withdrawal)
measure: Iodine consumes
timeFrame: 10 minutes (duration of urine recollection)
measure: Tumor classification type and modification after treatment
timeFrame: 40 minutes
Secondary outcomes:
measure: Disease-free survival
timeFrame: Every 6 months for 5 years
Other outcomes:
Locations:
city: Querétaro City
country: Mexico
facility: Hospital Médico TEC100
state: Queretaro
city: Querétaro
country: Mexico
facility: Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE
state: Queretaro
city: Querétaro
country: Mexico
facility: Hospital General Regional #1 IMSS
state: Queretaro
Study officials:
affiliation: Universidad Nacional Autonoma de Mexico
name: Carmen Aceves, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.