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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Tongue Carcinoma, 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

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Soy Isoflavones
* Other: Survey Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (soy isoflavones)<br>Patients receive soy isoflavones PO for approximately 14 days before undergoing surgery. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Soy Isoflavones<br>* Given PO<br>* Other names: Soybean Isoflavone Mixture;Other: Survey Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in p16 Methylation (% CpG Sites Methylated) in Tumor Tissue After Soy Isoflavone | The change in methylation 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, up to 42 days | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Alive at Follow-up | Overall survival at last follow-up will be determined. | Up to 24 months | 
| The Number of Participants Alive Without Relapse at Last Follow-up | Relapse-free survival will be determined at the last follow-up visit. | Up to 24 months |