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

Phase 2

Completed

Conditions: Recurrent Laryngeal Squamous Cell Carcinoma
Recurrent Laryngeal Verrucous Carcinoma
Stage I Hypopharyngeal Squamous Cell Carcinoma
Stage I Laryngeal Squamous Cell Carcinoma
Stage I Oropharyngeal Squamous Cell Carcinoma
Stage II Laryngeal Squamous Cell Carcinoma
Stage IV Hypopharyngeal Squamous Cell Carcinoma
Stage IVA Laryngeal Squamous Cell Carcinoma
Recurrent Lip and Oral Cavity Squamous Cell Carcinoma
Recurrent Hypopharyngeal Squamous Cell Carcinoma

Interventions: Other: Laboratory Biomarker Analysis
Drug: Soy Isoflavones
Other: Survey Administration

Brief 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.

Detailed 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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Treatment (soy isoflavones)	Survey Administration	Patients receive soy isoflavones PO for approximately 14 days before undergoing surgery.
Treatment (soy isoflavones)	Laboratory Biomarker Analysis	Patients receive soy isoflavones PO for approximately 14 days before undergoing surgery.
Treatment (soy isoflavones)	Soy Isoflavones	Patients receive soy isoflavones PO for approximately 14 days before undergoing surgery.

Primary Outcome Measures

Name	Time	Method
Mean Percent Change in p16 Methylation (% CpG Sites Methylated) in Tumor Tissue After Soy Isoflavone	From baseline to surgery, up to 42 days	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.
Correlations of Tumor p16 Methylation Status With Serum/Saliva Markers of p16, IL6, and VEGF	Up to 12 months	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.

Secondary Outcome Measures

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

Locations (3): 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, United States