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

February 18, 2020 updated by: Amit Agrawal, Ohio State University Comprehensive Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Detailed Description

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 cavity scrapings, blood, urine, and saliva samples are collected periodically for laboratory analyses.

After completion of study treatment, some patients are followed up at weeks 1-5 and then at 2, 6, 12, and 18 months.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Eligible subjects includes all adult HN cancer patients who have been previously diagnosed with Stage 1-4 and in-situ squamous cell carcinoma within the past 36 months (mos); with or without further adjuvant therapy and have been determined to be disease free at the time of consent
  • Patients must be able to take nutrition/medications orally
  • Have no prior history of intolerance or allergy to berry or berry-containing products
  • Patients taking cyclooxygenase (COX)-1/COX-2 inhibitors (Indomethacin, Ibuprofen, celebrex) chronically, herbal supplements, who cannot be taken off the medication/supplement due to their clinical condition are eligible to participate in the study but should document daily doses of these medications in their logbooks

Exclusion Criteria:

  • History of intolerance (including hypersensitivity or allergy) to berry or berry-containing products
  • Inability to take oral nutrition/liquids or history of aspiration pneumonia
  • Pregnant women: Although there are no known adverse effects of black raspberries upon the fetus, if patients become pregnant during period of lyophilized black raspberries (LBR) administration, then LBR will be discontinued and patient will be removed from the study; we should however emphasize, given this is a food based-study, that risks are likely extremely low even though a participant should become pregnant; as such, we are not recommending active contraception for women, but rather if participants become pregnant, that they notify their study doctor, and that they will likely be removed from study; there are no expected or logical risks if men were to father a child, and as such, no contraception will be recommended for men
  • Inability to grant informed consent
  • Strict Vegetarians will be excluded from the study; it was found that consuming one portion per day of fruit or vegetables resulted in a significant decrease in oral cancer incidence; in those persons consuming multiple portions each day, there was a 50% reduction in risk; we assume that strict vegetarians will consume multiple portions each day of foods with chemopreventive activity and therefore inclusion of these individuals would have a negative impact on the study; there are several reports in the literature that herbal or multivitamin/mineral supplements have no effect on oral cancer incidence

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Arm I (Lozenge placebo)
Patients receive lozenge placebo PO QID.
Correlative studies
Ancillary studies
Receive lozenge placebo PO
Other Names:
  • PLCB
Receive Saliva Substitute placebo PO
Other Names:
  • PLCB
EXPERIMENTAL: Arm II (LBR lozenge)
Patients receive lyophilized black raspberries lozenge PO (8gms/day)
Correlative studies
Ancillary studies
Receive LBR lozenge PO
Other Names:
  • cancer chemoprevention
  • chemoprevention of cancer
Receive LBR Saliva Substitute PO
Other Names:
  • cancer chemoprevention
  • chemoprevention of cancer
PLACEBO_COMPARATOR: Arm III (Saliva Substitute placebo)
Patients receive Saliva Substitute placebo PO QID.
Correlative studies
Ancillary studies
Receive lozenge placebo PO
Other Names:
  • PLCB
Receive Saliva Substitute placebo PO
Other Names:
  • PLCB
EXPERIMENTAL: Arm IV (LBR Saliva Substitute)
Patients receive lyophilized black raspberries Saliva Substitute PO (8gms/day).
Correlative studies
Ancillary studies
Receive LBR lozenge PO
Other Names:
  • cancer chemoprevention
  • chemoprevention of cancer
Receive LBR Saliva Substitute PO
Other Names:
  • cancer chemoprevention
  • chemoprevention of cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Define tolerability and potential adverse effects of long-term black raspberry administration of post-surgical HN cancer patients
Time Frame: up to 6 months
Use diaries and collection of "empties" over 6-month treatment period. Test both measures simultaneously using global test. Two measures tested individually at alpha=0.05 if global test is significant. First check for interaction effect between dose and delivery with double-sided test at alpha=0.01. If that isn't significant, use data from both doses to perform a double-sided alpha=0.05 on difference in compliance between delivery methods. Dose response effect in compliance also tested. Exploring for interaction effects with continued tobacco use vs not and oral cavity patients vs others.
up to 6 months
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
A double-sided test at alpha=0.05 and a mean summary across the repeated measures to test the difference in delivery methods will be used. Relationship between diary compliance and empties records and the two berry components measures over time will be modeled. The critical statistical result from this analysis will be the degree to which the individual patient's trends in the compliance measures correlate with the trends for the two components measured. Interaction effects with continued tobacco use will also be checked.
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.
up to 2 years
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.
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 4, 2007

Primary Completion (ACTUAL)

September 17, 2014

Study Completion (ACTUAL)

September 17, 2014

Study Registration Dates

First Submitted

October 27, 2011

First Submitted That Met QC Criteria

November 9, 2011

First Posted (ESTIMATE)

November 10, 2011

Study Record Updates

Last Update Posted (ACTUAL)

February 20, 2020

Last Update Submitted That Met QC Criteria

February 18, 2020

Last Verified

February 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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