Other Benign Neoplasm of Skin, UnspecifiedPhase 2NCT00601640
Eflornithine and/or Diclofenac in Treating Patients With Sun-Damaged Skin
A Phase 2 study testing Diclofenac Na gel and Eflornithine HCL ointment in people with Other Benign Neoplasm of Skin, Unspecified, run by University of Arizona at 3 sites in United States.
Trial summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of eflornithine and diclofenac may stop cancer from growing in patients with sun-damaged skin. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Other Benign Neoplasm of Skin, Unspecified
- What is being tested?
- Diclofenac Na gel and Eflornithine HCL ointment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2007to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Visible sun-induced damage to the skin as assessed by the study dermatologists
- No inflammation of the skin on the lateral forearms
- No more than 10 actinic keratoses on the left forearm, and no actinic keratoses in the treatment area
- Resident of Pima or an adjoining Southern Arizona county
- History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin at any site other than the left forearm allowed if excision or topical treatment was completed more than 30 days ago (60 days for radiotherapy)
- History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin on the left forearm allowed 6 months after treatment is completed
Show all 25Show fewer
- Must agree to avoid sun exposure to the left forearm as much as possible
- Not pregnant or nursing
- Not moderately to highly immunosuppressed by virtue of medication or disease, except for mildly suppressive disorders (e.g., diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma)
- No serious concurrent illness that could interfere with study participation
- No active peptic ulcer disease, bleeding disorder, renal failure (creatinine > 2.0 mg/dL), or porphyria
- No known hypersensitivity to diclofenac sodium, eflornithine, acetylsalicylic acid, or NSAIDS
- No evidence of serious underlying medical conditions as demonstrated by abnormal values on baseline laboratory assessment
- More than 6 months since prior chemotherapy and in complete remission
- More than 60 days since prior and no concurrent oral diclofenac sodium (Cataflam®, Voltaren®, Voltaren-XR®) or combination of diclofenac and misoprostol (Arthrotec®)
- More than 60 days since prior and no concurrent IV eflornithine hydrochloride
- More than 30 days since prior and no concurrent topical retinoids, steroids, imiquimod (Aldara®), aminolevulinic acid HCl (Levulan®), eflornithine (Vaniqa®), diclofenac sodium gel (Solaraze®), or fluorouracil at any site
- More than 30 days since prior and no concurrent topical medication, other than emollients or sunscreens, on the left forearm
- Not undergoing concurrent bone marrow or solid organ transplant
- No concurrent immunosuppressive therapy (e.g., systemic chemotherapy or rheumatologic agents such as infliximab [Remicade®])
- No concurrent sunscreen use to the left forearm
- No concurrent active therapy for any invasive cancer
- No concurrent NSAIDs for more than 14 days per month for arthritic and other pain conditions
- Concurrent prednisone or other steroids with doses up to 20 mg/day (or the equivalent dose) allowed
- At least 30 days since prior and no concurrent enrollment on other investigational drug or device trial
Who cannot join
- Individuals receiving concurrent topical therapy with retinoids, steroids, 5-fluorouracil, Levulan, Vaniqa (eflornithine), Solaraze, or Imiquimod (Aldara®) within 30 days prior to study enrollment will be excluded. Subjects may be reconsidered for eligibility 30 days after the last topical treatment.
- Individuals who have had treatment for basal cell carcinoma or squamous cell carcinoma of the skin of the left forearm within six months prior to evaluation for the study will not be eligible. If interested, these subjects will be encouraged to return for re-evaluation once the six-month period is over.
- Individuals who are moderately to highly immunosuppressed by virtue of medication or disease will not be allowed to participate. This category includes individuals undergoing bone marrow or solid organ transplant, or receiving immunosuppressive therapy such as systemic chemotherapy or rheumatologic agents such as infliximab (Remicade®). However, individuals with mildly suppressive disorders such as diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma will be eligible for participation. Doses up to 20 mg of prednisone per day or the equivalent dose of other steroids will be allowed.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Tucson, Arizona, 85258
Veterans Affairs Medical Center - Tucson
Tucson, Arizona, 85723
Arizona Cancer Center at University of Arizona Health Sciences Center
Tucson, Arizona, 85724-5024
About this study
Official title: Phase IIB Study to Evaluate the Safety and Efficacy of Topical Difluoromethylornithine and Topical Diclofenac in the Treatment of Sun-Damaged Skin on the Forearm
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of eflornithine and diclofenac may stop cancer from growing in patients with sun-damaged skin.
PURPOSE: This randomized phase II trial is studying the side effects and how well eflornithine works compared with diclofenac, given alone or together, in treating patients with sun-damaged skin.
Read the detailed description
OBJECTIVES:
Primary
- To determine if combination therapy with topical eflornithine hydrochloride ointment and topical diclofenac sodium gel over 3-months increases the efficacy versus either agent used alone in the treatment of moderately sun-damaged skin.
Secondary
- To evaluate the safety of sequential administration of topical eflornithine hydrochloride ointment and topical diclofenac sodium gel.
- To determine the correlation of karyometric changes with histopathologic, immunohistochemical, clinical, and genetic polymorphism data.
- To obtain materials for microarray analysis.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
- Eflornithine hydrochloride : Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90.
- Diclofenac sodium : Patients apply topical diclofenac sodium gel to their left forearm once daily on days 1-90.
- Eflornithine hydrochloride/Diclofenac sodium : Patients apply topical eflornithine hydrochloride ointment as in arm I twice daily and topical diclofenac sodium gel as in arm II once daily on days 1-90.
Prior to treatment, three 4-mm punch biopsies are taken from the skin of the left lateral forearm for assessment of histopathology, the cyclooxygenase-2 enzyme and p53 expression, apoptosis, and nuclear chromatin karyometry. Tissue is also obtained for future use in microarray analysis. Blood is drawn for assessment of ornithine decarboxylase polymorphisms and for banking for subsequent studies. Biopsies are repeated 2-3 weeks after completion of treatment.
Digital photographs are taken at baseline and 1-2 weeks after completion of study therapy to document improvement of sun damage, appearance of new skin lesions, and toxicity.
- Being tested
- Diclofenac Na gel, Eflornithine HCL ointment
- Keywords
- skin cancer
- Medical subject headings
- Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diclofenac Na gelDrug
Also called Solaraze
Given topically twice daily on days 1-90
Eflornithine HCL ointmentDrug
Also called Vaniqa
Given topically twice daily on days 1-90
| Study group | Role | What they receive |
|---|---|---|
| Eflornithine HCL | Experimental | Patients apply Eflornithine HCL ointment to their left forearm twice daily on days 1-90. Receives: Drug: Eflornithine HCL ointment |
| Diclofenac Na | Active comparator | Patients apply topical Diclofenac Na gel to their left forearm once daily on days 1-90. Receives: Drug: Diclofenac Na gel |
| Eflornithine HCL and Diclofenac Na | Experimental | Eflornithine HCl ointment and Diclofenac Na gel applied twice and once daily, respectively on days 1-90. Receives: Drug: Diclofenac Na gel; Drug: Eflornithine HCL ointment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Putrescine Over 3 Months
Putrescine is measured in nmole/g skin per biopsy. Baseline and End of Study biopsies were measured and the change was produced by subtracting baseline levels from End of Study levels. There was one baseline biopsy and one End of Study biopsy per participant.
Measured: 3 months
Safety of Combination Therapy With Topical Eflornithine Hydrochloride Ointment and Topical Diclofenac Sodium Gel Over 3-months
Adverse events were compared across three treatment groups by severity determined by the clinician. All adverse events were resolved by the end of follow up.
Measured: 3 months
Secondary outcomes (1)
Change in Histologic Score Diagnosis and Treatment Group
Change scores were computed by subtracting baseline histologic score from End of Study histologic score. Slides were formalin fixed. Histologic Score has been developed by this research group over the course of Grant (reference below). A standardized form captures data on the following criteria: basal or suprabasilar pleomorphism (atypia); inflammation; hyperkeratosis; parakeratosis. The atypia and inflammation were rated as: none (0), mild to moderate(1), and severe (2). The remaining criteria were rated as present (1) or absent (0). Histologic Scores were computed by adding together the codes for the histologic criteria. Higher scores reflected higher level of epidermal /dermal damage.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2008 (estimated)
- Study startJan 2007
- Primary completionFeb 2010
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Other Benign Neoplasm of Skin, UnspecifiedStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Joanne M. Jeter, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00601640
- Sponsor's protocol ID
- 07-0032-04
- Other IDs
- P30CA023074, P01CA027502, UARIZ-BIO-06182, 07-0032-04
- Status last verified
- Feb 2017
- First submitted
- 22 Jan 2008
- Last updated
- 23 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bozzo P, Saboda K, Einspahr JG, Ranger-Moore J, Farmer ER, Cockerell CJ, Elder DE, Bangert JL, Hart N, Kramer CB, Alberts DS. Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies. Anal Quant Cytol Histol. 2003 Oct;25(5):285-92.
PubMed 14603727Jeter JM, Curiel-Lewandrowski C, Stratton SP, Myrdal PB, Warneke JA, Einspahr JG, Bartels HG, Yozwiak M, Bermudez Y, Hu C, Bartels P, Alberts DS. Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm. Cancer Prev Res (Phila). 2016 Feb;9(2):128-34. doi: 10.1158/1940-6207.CAPR-15-0232. Epub 2015 Dec 28.
PubMed 26712942
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIB Study to Evaluate the Safety and Efficacy of Topical Difluoromethylornithine and Topical Diclofenac in the Treatment of Sun-Damaged Skin on the Forearm
- ClinicalTrials.gov ID
- NCT00601640
- Acronym / sponsor ID
- 07-0032-04
- Keywords
- skin cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2007
- Primary completion
- Feb 2010 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 28 Jan 2008 (estimated)
- Results
- Posted 23 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of eflornithine and diclofenac may stop cancer from growing in patients with sun-damaged skin.
PURPOSE: This randomized phase II trial is studying the side effects and how well eflornithine works compared with diclofenac, given alone or together, in treating patients with sun-damaged skin.
Detailed description
OBJECTIVES:
Primary
- To determine if combination therapy with topical eflornithine hydrochloride ointment and topical diclofenac sodium gel over 3-months increases the efficacy versus either agent used alone in the treatment of moderately sun-damaged skin.
Secondary
- To evaluate the safety of sequential administration of topical eflornithine hydrochloride ointment and topical diclofenac sodium gel.
- To determine the correlation of karyometric changes with histopathologic, immunohistochemical, clinical, and genetic polymorphism data.
- To obtain materials for microarray analysis.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
- Eflornithine hydrochloride : Patients apply topical eflornithine hydrochloride ointment to their left forearm twice daily on days 1-90.
- Diclofenac sodium : Patients apply topical diclofenac sodium gel to their left forearm once daily on days 1-90.
- Eflornithine hydrochloride/Diclofenac sodium : Patients apply topical eflornithine hydrochloride ointment as in arm I twice daily and topical diclofenac sodium gel as in arm II once daily on days 1-90.
Prior to treatment, three 4-mm punch biopsies are taken from the skin of the left lateral forearm for assessment of histopathology, the cyclooxygenase-2 enzyme and p53 expression, apoptosis, and nuclear chromatin karyometry. Tissue is also obtained for future use in microarray analysis. Blood is drawn for assessment of ornithine decarboxylase polymorphisms and for banking for subsequent studies. Biopsies are repeated 2-3 weeks after completion of treatment.
Digital photographs are taken at baseline and 1-2 weeks after completion of study therapy to document improvement of sun damage, appearance of new skin lesions, and toxicity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Eflornithine HCL | Experimental | Drug: Eflornithine HCL ointmentPatients apply Eflornithine HCL ointment to their left forearm twice daily on days 1-90. |
| Diclofenac Na | Active comparator | Drug: Diclofenac Na gelPatients apply topical Diclofenac Na gel to their left forearm once daily on days 1-90. |
| Eflornithine HCL and Diclofenac Na | Experimental | Drug: Diclofenac Na gel, Drug: Eflornithine HCL ointmentEflornithine HCl ointment and Diclofenac Na gel applied twice and once daily, respectively on days 1-90. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Visible sun-induced damage to the skin as assessed by the study dermatologists
- No inflammation of the skin on the lateral forearms
- No more than 10 actinic keratoses on the left forearm, and no actinic keratoses in the treatment area
- Resident of Pima or an adjoining Southern Arizona county
- History of treated basal cell carcinoma and/or squamous cell carcinoma of the skin at any site other than the left forearm allowed if excision or topical treatment was completed more than 30 days ago (60 days for radiotherapy)
Key exclusion criteria (3 listed)
- Individuals receiving concurrent topical therapy with retinoids, steroids, 5-fluorouracil, Levulan, Vaniqa (eflornithine), Solaraze, or Imiquimod (Aldara®) within 30 days prior to study enrollment will be excluded. Subjects may be reconsidered for eligibility 30 days after the last topical treatment.
- Individuals who have had treatment for basal cell carcinoma or squamous cell carcinoma of the skin of the left forearm within six months prior to evaluation for the study will not be eligible. If interested, these subjects will be encouraged to return for re-evaluation once the six-month period is over.
- Individuals who are moderately to highly immunosuppressed by virtue of medication or disease will not be allowed to participate. This category includes individuals undergoing bone marrow or solid organ transplant, or receiving immunosuppressive therapy such as systemic chemotherapy or rheumatologic agents such as infliximab (Remicade®). However, individuals with mildly suppressive disorders such as diabetes mellitus or on mildly immunosuppressive therapy such as inhaled steroids for asthma will be eligible for participation. Doses up to 20 mg of prednisone per day or the equivalent dose of other steroids will be allowed.
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 |
|---|---|---|
| Diclofenac Na gelAlso: SolarazeGiven topically twice daily on days 1-90 | Drug | Diclofenac Na, Eflornithine HCL and Diclofenac Na |
| Eflornithine HCL ointmentAlso: VaniqaGiven topically twice daily on days 1-90 | Drug | Eflornithine HCL, Eflornithine HCL and Diclofenac Na |
Primary outcome
Changes in Putrescine Over 3 Months
Time frame: 3 months
Putrescine is measured in nmole/g skin per biopsy. Baseline and End of Study biopsies were measured and the change was produced by subtracting baseline levels from End of Study levels. There was one baseline biopsy and one End of Study biopsy per participant.
Safety of Combination Therapy With Topical Eflornithine Hydrochloride Ointment and Topical Diclofenac Sodium Gel Over 3-months
Time frame: 3 months
Adverse events were compared across three treatment groups by severity determined by the clinician. All adverse events were resolved by the end of follow up.
1 secondary outcome
Change in Histologic Score Diagnosis and Treatment Group
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14603727Bozzo P, Saboda K, Einspahr JG, Ranger-Moore J, Farmer ER, Cockerell CJ, Elder DE, Bangert JL, Hart N, Kramer CB, Alberts DS. Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies. Anal Quant Cytol Histol. 2003 Oct;25(5):285-92.
- Derived from this study: PubMed 26712942Jeter JM, Curiel-Lewandrowski C, Stratton SP, Myrdal PB, Warneke JA, Einspahr JG, Bartels HG, Yozwiak M, Bermudez Y, Hu C, Bartels P, Alberts DS. Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm. Cancer Prev Res (Phila). 2016 Feb;9(2):128-34. doi: 10.1158/1940-6207.CAPR-15-0232. Epub 2015 Dec 28.
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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.
Joanne M. Jeter, MD principal investigator
University of Arizona
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diclofenac Na gel and Eflornithine HCL ointment in people with Other Benign Neoplasm of Skin, Unspecified, run by University of Arizona at 3 sites 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 25 inclusion and 3 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 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Yes. Results are posted in the registry (first posted 23 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Putrescine Over 3 Months (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00601640, which also lists 2 linked publications.
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 23 Mar 2017.