Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Gene Expression Profiling and Phototoxicity in Adults and Children Exposed to Ultraviolet Radiation

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Biomarker/Laboratory analysis, Natural history/Epidemiology Active 8 and over NCI NCI-06-C-0198 NCI-P6963, NCT00411008

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Determine the global gene expression profiles of phototoxic skin reactions in healthy volunteers treated with doxycycline and compare these expression profiles with the expression profiles of skin exposed to ultraviolet radiation in the absence of doxycycline.
2. Characterize voriconazole-related phototoxicity in participants utilizing phototesting.
3. Determine if participants with phototoxicity related to voriconazole receive reasonable phototoxic protection from the use of sunblock.

Secondary

1. Determine the relationship between voriconazole phototoxicity and pharmacogenomics (cytochrome P450 isoenzyme CYP2C19).
2. Determine the role of UVA (320-400 nm) and visible light in phototoxicity reactions associated with doxycycline and voriconazole.

Entry Criteria

Disease Characteristics:

• Meets 1 of the following criteria:
  • Scheduled to begin voriconazole therapy OR previously received OR currently receiving chronic voriconazole therapy
    • 8 years of age and over
    • Any skin phototype
    • Unexposed skin available for testing (no extensive skin disease) (for participants who are scheduled to begin voriconazole therapy)
      • Test sites for solar-stimulated ultraviolet radiation (ssUVR), UVA, and visible light exposures must be devoid of sunburn, suntan, scars, active dermal lesions, prior radiotherapy exposure, or uneven skin tone
      • Presence of nevi allowed provided they will not interfere with study results
      • Excess hair allowed if clipped or shaved
    • No history of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria (for participants who are scheduled to begin voriconazole therapy)
      • Prior remote history of phototoxicity reaction allowed
    • No history of keloid formation (for adult participants who are scheduled to begin voriconazole therapy and are undergoing modified shave biopsy)
  • Healthy volunteer
    • Age 18 to 45 years
    • Skin phototype II
    • Antinuclear antibodies/extractable nuclear antigen < 3
    • No history of idiopathic abnormal response to sunlight, such as polymorphic light eruption or solar urticaria
      • Prior remote history of phototoxicity reaction allowed
    • Unexposed skin available for testing (no extensive skin disease)
      • Test sites for ssUVR, UVA, and visible light exposures must be devoid of sunburn, suntan, scars, active dermal lesions, prior radiotherapy exposure, or uneven skin tone
      • Presence of nevi allowed provided they will not interfere with study results
      • Excess hair allowed if clipped or shaved
    • No history of keloid formation

Prior/Concurrent Therapy:

• See Disease Characteristics
• More than 7 days or 7 half-lives of phototesting (whichever is longer) since prior and no concurrent systemic medication, herbal supplements, or vitamins that are known to be associated with abnormal light response or effect cytochrome P450 enzymes (for healthy volunteers)
• No concurrent medications, herbal supplements, vitamins, or compounds containing bismuth subsalicylate (e.g., Pepto-Bismol) (for healthy volunteers)

Patient Characteristics:

• Not pregnant or nursing
• Fertile participants must use effective contraception
• No confounding past or present medical illness that, in the opinion of the investigator, would increase risk for study participation, including any of the following:
  • History of graft-vs-host disease
  • Receiving concurrent chemotherapy or completed chemotherapy within the past 2 weeks with known photoexacerbating agents (e.g., alkylating agents, doxorubicin hydrochloride, methotrexate, or cisplatin)
  • Received prior radiotherapy to the intended sites for phototesting
• No history of allergic reaction to lidocaine (for healthy volunteers OR for adult participants who are scheduled to begin voriconazole therapy and are undergoing modified shave biopsy)
• No allergy to tetracycline (for healthy volunteers)
• Liver function profile normal (for healthy volunteers)
  • No history of liver disease or hepatitis
• Willing to avoid excessive sun exposure and tanning equipment for 6 weeks prior to, during, and for 1 week after study participation

Expected Enrollment

A total of 195 participants will be accrued for this study.

Outcomes

Global gene expression profiles of phototoxic skin reactions in healthy volunteers treated with doxycycline
Comparison of gene expression profiles of phototoxic skin reactions in healthy volunteers treated with doxycycline with gene expression profiles of skin exposed to ultraviolet radiation in the absence of doxycycline
Voriconazole-related phototoxicity utilizing phototesting
Phototoxic protection from the use of sunblock in participants with phototoxicity related to voriconazole

Relationship between voriconazole phototoxicity and pharmacogenomics
Role of UVA (320-400 nm) and visible light in phototoxicity reactions associated with doxycycline and voriconazole

Outline

This is a pilot study.

• Healthy volunteers: On day 1, participants undergo baseline phototesting comprising solar-simulated ultraviolet radiation (ssUVR), UVA, and visible light exposures on sun-protected skin and pre- and post-exposure photographic documentation. On day 2, participants undergo additional photographic documentation, colorimeter measurements of non-exposed laterally adjacent skin and post-exposure sites with minimal visible erythema, and biopsies (using a modified shave biopsy technique) of exposed and unexposed skin. Participants receive oral doxycycline twice daily on days 3-5. On day 6, participants receive the final dose (7th dose of oral doxycycline) followed 2 hours later by blood draws (for liver function testing and pharmacologic analyses). Participants also undergo phototesting comprising ssUVR, UVA, and visible light exposure and pre- and post-exposure photographic documentation. On day 7, participants undergo additional photographic documentation, colorimeter measurements, and biopsies of exposed and unexposed skin.

  Skin biopsies are examined by gene expression microarray studies.




• Participants currently receiving, previously received, or scheduled to receive voriconazole: On days 1 and 2, participants undergo baseline phototesting, pre- and post-exposure photographic documentation, and colorimeter measurements as in healthy volunteers. Biopsies are optional. On or about day 10 (after ≥ 7 days of receiving oral voriconazole), participants receive a dose of oral voriconazole followed 1 hour later by blood draws (for liver function testing and pharmacologic analyses). Participants also undergo sunscreen phototesting comprising ssUVR, UVA, and visible light exposure on skin protected with an over-the-counter sunscreen and sunblock, and pre- and post-exposure photographic documentation. On day 11, participants undergo additional photographic documentation, colorimeter measurements, and optional biopsies.

  Blood is examined for cytochrome P450 genotyping (CYP2C19 gene variations) via restriction fragment-length polymorphism-based techniques or nucleotide sequencing.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Maria Turner, MD, Principal investigator		Ph: 301-496-7737

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Registry Information
Official Title		A Pilot Pediatric/Adult Study of Gene Expression Profiling and Clinical Characterization of Phototoxicity
Trial Start Date		2006-06-01
Trial Completion Date		2008-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00411008
Date Submitted to PDQ		2006-07-24
Information Last Verified		2008-04-06

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