Soy Isoflavones in Preventing Head and Neck Cancer Recurrence in Patients With Stage I-IV Head and Neck Cancer Undergoing Surgery

Recurrent Laryngeal Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase II Trial of Preoperative Soy Isoflavone Supplementation and Molecular Markers in the Prevention of Head and Neck Squamous Carcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02007200
• Other study ID #: NCI-2011-03618
• Secondary ID: NCI-2011-03618UM
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 4, 2013
• Last updated: September 28, 2015
• Start date: July 2009

Study information

• Verified date: June 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase II clinical trial studies how well soy isoflavones work in preventing head and neck cancer in patients with stage I-IV head and neck cancer undergoing surgery. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of soy isoflavones may prevent head and neck cancer recurrence.

Description:

PRIMARY OBJECTIVES:

I. To determine if short term, preoperative (300 mg/day x 14 treatment days) soy isoflavone supplementation modulates p16 methylation (% CpG sites methylated) and expression of p16, cyclooxygenase 2 [COX-2], vascular endothelial growth factor receptor [VEGF], epidermal growth factor receptor [EGFR], interleukin-6 [IL6], p53 and B-cell lymphoma-extra large [Bcl-xL] in tumor and non-tumor adjacent mucosa of patients with head and neck squamous carcinoma undergoing curative tumor resection.

II. To estimate correlations of tumor p16 methylation (% CpG sites methylated) with expression of p16 and levels of, IL6, VEGF, and 15-F2t-isoprostane in serum and saliva.

SECONDARY OBJECTIVES:

I. Describe the toxicity of short-term, preoperative treatment with soy isoflavone.

II. To determine overall and relapse-free survival.

OUTLINE:

Patients receive soy isoflavones orally (PO) for approximately 14 days before undergoing surgery.

After completion of treatment, patients are followed up, within the routine cancer management schedule, at 3, 6, 12, and 24 months.

Other known NCT identifiers

• NCT01028001

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 44
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 79 Years

Eligibility

Inclusion Criteria:

• Patients must have pathologically-confirmed, resectable, squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx

• Disease must be Stage I, II, III or IVa

• Tumor must be potentially surgically resectable and curable with conventional surgery and radiation therapy

• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

• Patients must give documented informed consent to participate in this study

Exclusion Criteria:

• Documented evidence of distant metastases

• Ongoing acute medical condition such as uncontrolled coronary artery disease, emphysema, or diabetes mellitus that would preclude surgical resection

• Pregnancy or lactation; patients of child bearing age must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of soy administration

• A medical or psychiatric illness which would compromise the patient's ability to tolerate this treatment or comply with administration of study drug

• Patients residing in prison

• Any patient with a history of breast or ovarian cancer

• Allergy to soy products

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Recurrent Hypopharyngeal Squamous Cell Carcinoma
• Recurrent Laryngeal Squamous Cell Carcinoma
• Recurrent Laryngeal Verrucous Carcinoma
• Recurrent Lip and Oral Cavity Squamous Cell Carcinoma
• Recurrent Oral Cavity Verrucous Carcinoma
• Recurrent Oropharyngeal Squamous Cell Carcinoma
• Stage I Hypopharyngeal Squamous Cell Carcinoma
• Stage I Laryngeal Squamous Cell Carcinoma
• Stage I Laryngeal Verrucous Carcinoma
• Stage I Lip and Oral Cavity Squamous Cell Carcinoma
• Stage I Oral Cavity Verrucous Carcinoma
• Stage I Oropharyngeal Squamous Cell Carcinoma
• Stage II Hypopharyngeal Squamous Cell Carcinoma
• Stage II Laryngeal Squamous Cell Carcinoma
• Stage II Laryngeal Verrucous Carcinoma
• Stage II Lip and Oral Cavity Squamous Cell Carcinoma
• Stage II Oral Cavity Verrucous Carcinoma
• Stage II Oropharyngeal Squamous Cell Carcinoma
• Stage III Hypopharyngeal Squamous Cell Carcinoma
• Stage III Laryngeal Squamous Cell Carcinoma
• Stage III Laryngeal Verrucous Carcinoma
• Stage III Lip and Oral Cavity Squamous Cell Carcinoma
• Stage III Oral Cavity Verrucous Carcinoma
• Stage III Oropharyngeal Squamous Cell Carcinoma
• Stage IV Hypopharyngeal Squamous Cell Carcinoma
• Stage IVA Laryngeal Squamous Cell Carcinoma
• Stage IVA Laryngeal Verrucous Carcinoma
• Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma
• Stage IVA Oral Cavity Verrucous Carcinoma
• Stage IVA Oropharyngeal Squamous Cell Carcinoma
• Tongue Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Soy Isoflavones
Given PO

Other:
• Survey Administration
Ancillary studies

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in p16 methylation (% CpG sites methylated) and expression of p16, COX-2, VEGF, EGFR, IL6, p53 and BclxL in tumor and non-tumor adjacent mucosa	The change in the endpoints (p16 methylation and expression of p16, COX-2, VEGF, EGFR, IL6, p53 and Bcl-xL) will be analyzed in parallel using a linear repeated measures model. The fixed effects will be time (pre-treatment versus post-treatment), current smoking status (yes or no), their interaction, and tissue type (tumor or not). Satterthwaite's adjustment to the degrees of freedom will be applied to account for heteroscedasticity. The differential effect of soy isoflavone on tumor and non-tumor tissues between smokers and non-smokers will be assessed using linear contrasts.	From baseline to surgery	No
Primary	Correlations of tumor p16 methylation status with serum/saliva markers of p16, IL6, and VEGF	Each of the tumor and mucosal markers will be dependent variables in repeated measures models that include serum and saliva markers as predictors. Graphical analyses will be used to characterize possible nonlinear relationships between variables. Linear or nonlinear regression, as appropriate, will be used to characterize the relationship between the putative predictors and outcomes. Subset analyses, considering, for example, differences in relationships between tumor markers and serum and saliva markers between smokers and non-smokers will be performed by means of indicator variables.	Up to 12 months	No
Secondary	Incidence of observed toxicities	Adverse events observed in the pre-operative and immediate (30 day) post-operative period will be tabulated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade and description, assessed relationship to treatment, and demographic and baseline clinical variables. The analyses will be descriptive and no hypothesis tests are planned.	Up to 30 days after surgery	Yes
Secondary	Overall survival	Survival and relapse-free survival functions will be estimated using the product-limit (Kaplan-Meier) method, with appropriate confidence intervals, for the entire sample and for subsets defined by demographic and baseline clinical variables. In addition, proportional hazards (Cox) regression will be used to assess the potential of biomarker response to treatment as a predictor of survival and relapse-free survival. These analyses are strictly exploratory and hypothesis-generating.	Up to 24 months	No
Secondary	Relapse-free survival	Survival and relapse-free survival functions will be estimated using the product-limit (Kaplan-Meier) method, with appropriate confidence intervals, for the entire sample and for subsets defined by demographic and baseline clinical variables. In addition, proportional hazards (Cox) regression will be used to assess the potential of biomarker response to treatment as a predictor of survival and relapse-free survival. These analyses are strictly exploratory and hypothesis-generating.	Up to 24 months	No