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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amit Agrawal, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01469429
First received: October 27, 2011
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Salivary Gland Squamous Cell Carcinoma
Stage 0 Hypopharyngeal Cancer
Stage 0 Laryngeal Cancer
Stage 0 Lip and Oral Cavity Cancer
Stage 0 Nasopharyngeal Cancer
Stage 0 Oropharyngeal Cancer
Stage 0 Paranasal Sinus and Nasal Cavity Cancer
Stage I Salivary Gland Cancer
Stage I Squamous Cell Carcinoma of the Hypopharynx
Stage I Squamous Cell Carcinoma of the Larynx
Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage I Squamous Cell Carcinoma of the Nasopharynx
Stage I Squamous Cell Carcinoma of the Oropharynx
Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage I Verrucous Carcinoma of the Larynx
Stage I Verrucous Carcinoma of the Oral Cavity
Stage II Salivary Gland Cancer
Stage II Squamous Cell Carcinoma of the Hypopharynx
Stage II Squamous Cell Carcinoma of the Larynx
Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage II Squamous Cell Carcinoma of the Nasopharynx
Stage II Squamous Cell Carcinoma of the Oropharynx
Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage II Verrucous Carcinoma of the Larynx
Stage II Verrucous Carcinoma of the Oral Cavity
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Oral Cavity Squamous Cell Carcinoma
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Nasal Cavity and Paranasal Sinus Cancer
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Oral Cavity Squamous Cell Carcinoma
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Salivary Gland Cancer
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Oral Cavity Squamous Cell Carcinoma
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Paranasal Sinus and Nasal Cavity Squamous Cell Carcinoma
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Other: placebo
Other: laboratory biomarker analysis
Other: questionnaire administration
Drug: chemoprevention
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Food-Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Define tolerability and potential adverse effects of long-term black raspberry administration of post-surgical HN cancer patients [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Correlation between change in gene expression within key regulatory pathways and dose and delivery method [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 140
Study Start Date: September 2007
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm I (Lozenge placebo)
Patients receive lozenge placebo PO QID.
Other: placebo
Receive lozenge placebo PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Experimental: Arm II (LBR lozenge)
Patients receive lyophilized black raspberries lozenge PO (8gms/day)
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Drug: chemoprevention
Receive LBR lozenge PO
Other Names:
  • cancer chemoprevention
  • chemoprevention of cancer
Placebo Comparator: Arm III (Saliva Substitute placebo)
Patients receive Saliva Substitute placebo PO QID.
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Other: placebo
Receive Saliva Substitute placebo PO
Other Name: PLCB
Experimental: Arm IV (LBR Saliva Substitute)
Patients receive lyophilized black raspberries Saliva Substitute PO (8gms/day).
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Drug: chemoprevention
Receive LBR Saliva Substitute PO
Other Names:
  • cancer chemoprevention
  • chemoprevention of cancer

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469429

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: Amit Agrawal Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Amit Agrawal, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01469429     History of Changes
Other Study ID Numbers: OSU-07085, NCI-2011-03226
Study First Received: October 27, 2011
Last Updated: November 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
oral cancer

Additional relevant MeSH terms:
Carcinoma
Laryngeal Neoplasms
Carcinoma, Squamous Cell
Laryngeal Diseases
Mouth Neoplasms
Tongue Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Hypopharyngeal Neoplasms
Carcinoma in Situ
Carcinoma, Verrucous
Head and Neck Neoplasms
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Lip Neoplasms
Paranasal Sinus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Otorhinolaryngologic Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Neoplasms, Squamous Cell
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases

ClinicalTrials.gov processed this record on August 18, 2014