Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaPhase 1/2NCT01469429
Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.
A Phase 1/2 study testing laboratory biomarker analysis, questionnaire administration and chemoprevention in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Salivary Gland Squamous Cell Carcinoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Salivary Gland Squamous Cell Carcinoma, Stage 0 Hypopharyngeal Cancer
- What is being tested?
- laboratory biomarker analysis, questionnaire administration and chemoprevention
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Sep 2007to 17 Sep 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- Conditions
- 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
- Being tested
- placebo, laboratory biomarker analysis, questionnaire administration, chemoprevention
- Keywords
- oral cancer
- Medical subject headings
- Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Nasopharyngeal Neoplasms, Oropharyngeal Neoplasms, Salivary Gland Neoplasms, Squamous Cell Carcinoma of Head and Neck, Paranasal Sinus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboOther
Also called PLCB
Receive lozenge placebo PO
laboratory biomarker analysisOther
Correlative studies
questionnaire administrationOther
Ancillary studies
chemopreventionDrug
Also called cancer chemoprevention, chemoprevention of cancer
Receive LBR lozenge PO
chemopreventionDrug
Also called cancer chemoprevention, chemoprevention of cancer
Receive LBR Saliva Substitute PO
placeboOther
Also called PLCB
Receive Saliva Substitute placebo PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Lozenge placebo) | Placebo comparator | Patients receive lozenge placebo PO QID. Receives: Other: placebo; Other: laboratory biomarker analysis; Other: questionnaire administration |
| Arm II (LBR lozenge) | Experimental | Patients receive lyophilized black raspberries lozenge PO (8gms/day) Receives: Other: laboratory biomarker analysis; Other: questionnaire administration; Drug: chemoprevention |
| Arm III (Saliva Substitute placebo) | Placebo comparator | Patients receive Saliva Substitute placebo PO QID. Receives: Other: laboratory biomarker analysis; Other: questionnaire administration; Other: placebo |
| Arm IV (LBR Saliva Substitute) | Experimental | Patients receive lyophilized black raspberries Saliva Substitute PO (8gms/day). Receives: Other: laboratory biomarker analysis; Other: questionnaire administration; Drug: chemoprevention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Define tolerability and potential adverse effects of long-term black raspberry administration of post-surgical HN cancer patients
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.
Measured: 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.
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.
Measured: up to 2 years
Correlation between change in gene expression within key regulatory pathways and dose and delivery method
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.
Measured: up to 2 years
Sustainability of the measures within genes found to show significant berry effects beyond the 6-month exposure period
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.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study start4 Sep 2007
- Primary completion17 Sep 2014
- Study completion17 Sep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amit Agrawal, Ohio State University Comprehensive Cancer Center
- Investigators
- Amit Agrawal, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469429
- Sponsor's protocol ID
- OSU-07085
- Other IDs
- NCI-2011-03226
- Status last verified
- Feb 2020
- First submitted
- 27 Oct 2011
- Last updated
- 20 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Food-Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer
- ClinicalTrials.gov ID
- NCT01469429
- Acronym / sponsor ID
- OSU-07085
- Conditions
- 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
- Keywords
- oral cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 4 Sep 2007 (actual)
- Primary completion
- 17 Sep 2014 (actual)
- Study completion
- 17 Sep 2014 (actual)
- First posted
- 10 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
PRIMARY OBJECTIVES:
- 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm I (Lozenge placebo) | Placebo comparator | Other: placebo, Other: laboratory biomarker analysis, Other: questionnaire administrationPatients receive lozenge placebo PO QID. |
| Arm II (LBR lozenge) | Experimental | Other: laboratory biomarker analysis, Other: questionnaire administration, Drug: chemopreventionPatients receive lyophilized black raspberries lozenge PO (8gms/day) |
| Arm III (Saliva Substitute placebo) | Placebo comparator | Other: laboratory biomarker analysis, Other: questionnaire administration, Other: placeboPatients receive Saliva Substitute placebo PO QID. |
| Arm IV (LBR Saliva Substitute) | Experimental | Other: laboratory biomarker analysis, Other: questionnaire administration, Drug: chemopreventionPatients receive lyophilized black raspberries Saliva Substitute PO (8gms/day). |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboAlso: PLCBReceive lozenge placebo PO | Other | Arm I (Lozenge placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (Lozenge placebo), Arm II (LBR lozenge), Arm III (Saliva Substitute placebo), Arm IV (LBR Saliva Substitute) |
| questionnaire administrationAncillary studies | Other | Arm I (Lozenge placebo), Arm II (LBR lozenge), Arm III (Saliva Substitute placebo), Arm IV (LBR Saliva Substitute) |
| chemopreventionAlso: cancer chemoprevention, chemoprevention of cancerReceive LBR lozenge PO | Drug | Arm II (LBR lozenge) |
| chemopreventionAlso: cancer chemoprevention, chemoprevention of cancerReceive LBR Saliva Substitute PO | Drug | Arm IV (LBR Saliva Substitute) |
| placeboAlso: PLCBReceive Saliva Substitute placebo PO | Other | Arm III (Saliva Substitute placebo) |
Primary outcome
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2020.
- JameslineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amit Agrawal principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing laboratory biomarker analysis, questionnaire administration and chemoprevention in people with Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma and Salivary Gland Squamous Cell Carcinoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Define tolerability and potential adverse effects of long-term black raspberry administration of post-surgical HN cancer patients (time frame: up to 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2020.