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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.

Current Primary Outcome:

• Mean Percent Change in p16 Methylation (% CpG Sites Methylated) in Tumor Tissue After Soy Isoflavone [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome:

• 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 [ Time Frame: From baseline to surgery ]
  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.
• Correlations of Tumor p16 Methylation Status With Serum/Saliva Markers of p16, IL6, and VEGF [ Time Frame: 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.

Current Secondary Outcome:

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

Original Secondary Outcome:

• Overall survival [ Time Frame: Up to 24 months ]
  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.
• Relapse-free survival [ Time Frame: Up to 24 months ]
  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.
• Incidence of observed toxicities [ Time Frame: Up to 30 days after surgery ]
  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.

Dates:
Date Received: December 4, 2013
Date Started: July 2009
Date Completion:
Last Updated: September 1, 2016
Last Verified: September 2016