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

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.

• Laboratory Biomarker Analysis (Other): Correlative studies
• Soy Isoflavones (Drug), also known as NovaSoy, Solgen 40, Soy Isoflavone, Soybean Isoflavone Mixture: Given PO
• Survey Administration (Other): Ancillary studies

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 19 Years to 79 Years

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

Participant flow

Outcome results

• Mean Percent Change in p16 Methylation (% CpG Sites Methylated) in Tumor Tissue After Soy Isoflavone (Primary), Mean, Percent change: Treatment (Soy Isoflavones) 4.9 (-34.8 to 20.9) (p <0.005)
• Correlations of Tumor p16 Methylation Status With Serum/Saliva Markers of p16, IL6, and VEGF (Primary)
• The Number of Participants Alive at Follow-up (Secondary), Number, participants: Treatment (Soy Isoflavones) 29
• The Number of Participants Alive Without Relapse at Last Follow-up (Secondary), Number, participants: Treatment (Soy Isoflavones) 24

Adverse events

Serious adverse events by term

Other adverse events by term

10 more terms not shown.

• Greg Wolf, Principal investigator, University of Michigan Rogel Cancer Center

NIH grants: P30CA046592