Clinical Trial: Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Food-Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer

Brief Summary: This randomized phase I/II trial studies the side effects and best way to give lyophilized black raspberries in preventing oral cancer in high-risk patients previously diagnosed with stage I-IV or in situ head and neck cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of lyophilized black raspberries may prevent oral cancer. Studying samples of oral cavity scrapings, blood, urine, and saliva in the laboratory from patients receiving lyophilized black raspberries may help doctors learn more about changes that occur in DNA and the effect of lyophilized back raspberries on biomarkers.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the adherence of post-surgical head and neck (HN) cancer patients to clinical trial design expectations and define tolerability and potential adverse effects of long-term black raspberry administration in this patient cohort.

II. Determine the effects of dose and delivery vehicle on the degree of uptake of black raspberry components in target oral tissues of post-surgical HN cancer patients over time and determine the relationships between adherence/exposure data and uptake.

III. Determine the ability of black raspberries to modulate patterns of gene expression within key regulatory pathways in "at-risk normal" oral mucosa of post-surgical HN cancer patients that would favor the inhibition, delay or reversal of oral carcinogenesis.

IV. Determine the persistence of modulation of "berry-responsive genes" for 2 years following commencement of black raspberry treatment and preliminarily define rate of recurrence and second primary oral cancers in a former oral cancer patient sub-cohort.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive lozenge placebo orally (PO) four times daily (QID).

ARM II: Patients receive lyophilized black raspberries lozenge PO QID.

ARM III: Patients receive Saliva Substitute placebo PO QID.

ARM IV: Patients receive lyophilized black raspberries Saliva Substitute PO QID.

In all arms, treatment continues for 6 months. Oral cavi
Sponsor: Ohio State University Comprehensive Cancer Center

Current Primary Outcome:

  • Define tolerability and potential adverse effects of long-term black raspberry administration of post-surgical HN cancer patients [ Time Frame: up to 2 years ]
  • Effects of dose and delivery vehicle on the degree of uptake of black raspberry components in target oral tissues of post-surgical HN cancer patients over time and determine the relationships between adherence/exposure data and uptake. [ Time Frame: up to 2 years ]
  • Correlation between change in gene expression within key regulatory pathways and dose and delivery method [ Time Frame: up to 2 years ]
    Using qRT-PCR measurements for each of 8 genes. Multiple endpoint approach for each gene will be used. Linear mixed models will be used for the repeated measures. Global test at 0.05 to decide superior delivery method. Mean summary statistic across the repeated measures will be used. Interaction effect of dose and delivery tested. Test for interaction of tobacco use at 0.05. Proc Mixed used to estimate both within person (over time changes) and between person relationships across berry components and pathway measures.
  • Sustainability of the measures within genes found to show significant berry effects beyond the 6-month exposure period [ Time Frame: up to 2 years ]
    Slopes of change (toward baseline) estimated. Hypothesis testing to rule out chance as explanation of changes toward baseline in the berry exposed groups. Relationship between sustainability and the delivery dose studied. Effects on sustainability of continued or changing tobacco use will be estimated. Measures during extended follow-up that are clear indicators of efficacy will be collected.


Original Primary Outcome:

  • Define tolerability and potential adverse effects of long-term black raspberry administration of post-surgical HN cancer patients [ Time Frame: 2007-presesnt ]
  • Effects of dose and delivery vehicle on the degree of uptake of black raspberry components in target oral tissues of post-surgical HN cancer patients over time and determine the relationships between adherence/exposure data and uptake. [ Time Frame: 2007-present ]
  • Correlation between change in gene expression within key regulatory pathways and dose and delivery method [ Time Frame: 2007-present ]
    Using qRT-PCR measurements for each of 8 genes. Multiple endpoint approach for each gene will be used. Linear mixed models will be used for the repeated measures. Global test at 0.05 to decide superior delivery method. Mean summary statistic across the repeated measures will be used. Interaction effect of dose and delivery tested. Test for interaction of tobacco use at 0.05. Proc Mixed used to estimate both within person (over time changes) and between person relationships across berry components and pathway measures.
  • Sustainability of the measures within genes found to show significant berry effects beyond the 6-month exposure period [ Time Frame: 2007-present ]
    Slopes of change (toward baseline) estimated. Hypothesis testing to rule out chance as explanation of changes toward baseline in the berry exposed groups. Relationship between sustainability and the delivery dose studied. Effects on sustainability of continued or changing tobacco use will be estimated. Measures during extended follow-up that are clear indicators of efficacy will be collected.


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Ohio State University Comprehensive Cancer Center

Dates:
Date Received: October 27, 2011
Date Started: September 4, 2007
Date Completion: January 1, 2019
Last Updated: January 20, 2017
Last Verified: January 2017