Study to Determine the Maximum Tolerated Dose and Safety of PEP005 Topical Gel

This study has been completed.
Sponsor:
Information provided by:
Peplin
ClinicalTrials.gov Identifier:
NCT00239135
First received: October 12, 2005
Last updated: December 22, 2008
Last verified: December 2008
  Purpose

The purpose of this study is :

  • To determine the maximum tolerated dose (MTD) for PEP005 Topical Gel in patients with actinic keratoses.
  • To evaluate patients for clinical safety
  • To determine the systemic absorption of PEP005 Topical Gel

Condition Intervention Phase
Keratosis
Drug: PEP005
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose Escalation, Cohort Study to Determine the Maximum Tolerated Dose and Safety of PEP005 Topical Gel When Applied on Day 1 and Day 2 to Actinic Keratoses on the Shoulders, Chest, Back or Arms Followed by a Post-Treatment Follow-up Period Lasting at Four Weeks

Resource links provided by NLM:


Further study details as provided by Peplin:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD)

Secondary Outcome Measures:
  • Safety and clinical efficacy
  • Systemic absorption

Estimated Enrollment: 34
Study Start Date: September 2005
Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Detailed Description:

Actinic keratoses (AK) is a common skin condition characterized by rough, scaly patches or sores on the top layer of the skin which if left untreated can progress to skin cancer. Current treatments can cause scarring and hypopigmentation, be inconvenient, or require long treatment duration. Non-invasive alternative therapy for treatment of AK lesions is thus being researched.

This is an open label, dose escalation, cohort study to determine the maximum tolerated dose (MTD) of PEP005 Topical Gel, administered once daily for two consecutive days (90 ul gel applied topically over a 3 x 3cm template surrounding a target lesion), to patients with actinic keratoses (AK). The study will be conducted in one centre in the US. Three patients will be entered initially at the lowest dose level (0.01%) with up to an additional three patients to be entered in the event of a dose limiting toxicity (DLT) in the initial patients. DLT are defined as 'severe' local skin reactions observed by the Investigator, either prior to treatment on Day 2 ( following treatment on Day 1 ) or observed on Day 8 (following treatment on Day 2). Based on findings from phase I studies and the low systemic absorption found in non-clinical toxicokinetic evaluations, no systemic toxicity is anticipated.Once determined A total of 10 patients will be treated at the MTD in order to confirm it's determination. Based on findings from the phase I study, the starting dose will be 0.01% PEP005 Gel.

Secondary objectives of the study are (1) evaluate the clinical efficiency of PEP005 Topical Gel, when administered once daily for two consecutive days and (2) determine the systemic absorption of PEP005 Topical Gel at the MTD . Hematologic and biochemical assessments will be undertaken at the screening visit and at days 8 and 29 . Adverse events will be assessed at every study visit. Clinical response to treatment will be assessed at Days 8, 15 and 29.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female at least 18 years of age
  • One AK lesion selected for treatment on the shoulders, chest, back or arms
  • Longest diameter of the selected lesion between 3mm and 15mm
  • Screening laboratory values within the references ranges as defined by the laboratory or "out of range" test results that are clinically acceptable to the Investigator
  • Ability to follow study instructions and likely to complete all study requirements
  • Written informed consent has been obtained
  • Written Authorization for the Use and Release of Health and Research Study Information has been obtained
  • Agreement from the patient to allow photographs of the selected lesion to be taken and used as part of the study data package.

Exclusion Criteria:

  • Females of child bearing potential (a female is considered to be of childbearing potential unless she is post-menopausal, i.e no menses for at least 12 consecutive months or is without a uterus)
  • Actinic Keratoses selected for treatment that are hypertrophic
  • Location of the selected actinic keratoses lesion:

    1. within 5 cm of a scar
    2. within 5 cm of any actinic keratosis lesion not selected for treatment
    3. within 5 cm of an incompletely healed wound
    4. on the breast
    5. within 5 cm of an area previously treated with surgical excision
  • Presence of suspected basal cell carcinoma or squamous cell carcinoma within 5 cm of the selected treatment area
  • Presence of known or suspected metastatic disease
  • History or evidence of skin conditions other than AK which would interfere with the evaluation of the study medication (e.g eczema, unstable psoriasis, xeroderma pigmentosa)
  • Known sensitivity to any of the ingredients in the study medication
  • A cosmetic or therapeutic procedure (e.g liquid nitrogen, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) located within 10cm of the actinic keratosis lesion selected for treatment during three months prior to study entry or anticipated treatment within 10cm of the selected lesion during the study
  • Within four weeks prior to study entry, a cosmetic or therapeutic procedure located anywhere on the body
  • Within three months prior to the study entry, treatment with 5-flourouracil, imiquimod, diclofenac, masoprocol, or photodynamic therapy for lesions located within 10cm of the actinic keratosis lesion selected for treatment
  • Within four weeks prior to study entry, treatment with 5-flourouracil, imiquimod, masoprocol, or photodynamic therapy for lesion located anywhere on the body
  • Previous treatment with other immunomodulators (e.g vinblastine, podophyllin, colhamin, camptothecin), cytotoxic drugs (e;g cyclophosphamide, azathioprine, chlorambucil, nitrogen mustard, methotrexate), or interferon/interferon inducers (other than imiquimod)within four weeks prior to study entry
  • Previous treatment with psoralen plus UVA or use of UVB therapy within six months prior to study entry
  • Patients who require or desire excess or prolonged exposure to ultraviolet light(e.g sunlight, tanning beds) during the study
  • Use of medications that suppress the immune system within four weeks prior study entry (e.g cyclosporine, prednisone, methotrexate, alefacept, infliximab)
  • Within four weeks prior to study entry, use of topical retinoids or light chemical peels located within 10cm of the actinic keratosis lesion selected for treatment
  • Use of systemic retinoids (e.g isotretinoin, acitretin, bexarotene) within six months prior to study entry
  • Within four weeks prior to study entry, use of acid containing products (e.g salicylic acids or fruit acids such as alpha and beta hydroxy acids and glycolic acids). located within 10 cm of the actinic keratosis lesion selected for treatment
  • Anticipated need to use acid containing products on the treatment area during the study ( e.g salicylic acids or fruit acids, such as alpha and beta hydroxy acids and glycolic acids)
  • Concurrent disease that supresses the immune system(e.g HIV)
  • Uncontrolled systemic disease (e.g uncontrolled hypertension)
  • Anticipated need for surgery or hospitalization during the study
  • Current evidence of chronic alcohol or drug abuse
  • Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study
  • Patient has a condition or is in a situation which in the Investigator's opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patients participation in the study.
  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: NCT00239135

Locations
United States, Texas
Dermatology Associates of Tyler
Tyler, Texas, United States, 75703
Sponsors and Collaborators
Peplin
Investigators
Principal Investigator: Lawrence Anderson, MD, F.A.C.P
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00239135     History of Changes
Other Study ID Numbers: PEP005-004
Study First Received: October 12, 2005
Last Updated: December 22, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Peplin:
Actinic Keratosis
Topical
Maximum Tolerated Dose
Solar Keratosis
Sun Spots
Dermatology

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Neoplasms
Precancerous Conditions
Skin Diseases

ClinicalTrials.gov processed this record on October 23, 2014