RATIONALE: Ultraviolet light therapy uses light and drugs that make cancer cells more sensitive to light to kill tumor cells. It is not yet known whether ultraviolet light therapy is more effective with or without bexarotene in treating mycosis fungoides.

PURPOSE: Randomized phase III trial to compare the effectiveness of ultraviolet light therapy using methoxsalen with or without bexarotene in treating patients who have mycosis fungoides.

Condition	Treatment or Intervention	Phase
stage I mycosis fungoides/Sezary syndrome stage II mycosis fungoides/Sezary syndrome recurrent mycosis fungoides/Sezary syndrome	Drug: bexarotene  Drug: methoxsalen  Procedure: UV light therapy  Procedure: chemotherapy  Procedure: phototherapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the cumulative dose of ultraviolet A light required to achieve a complete clinical response (CCR) in patients with mycosis fungoides treated with ultraviolet A light therapy with methoxsalen (PUVA) with or without bexarotene.
• Compare the overall response rate (CCR and partial response) in patients treated with these regimens.
• Compare the duration of CCR and time to relapse of patients treated with these regimens.
• Compare the number of PUVA sessions necessary to achieve a CCR in these patients.
• Determine the percentage of dropouts by patients treated with these regimens.
• Determine the safety of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, age (60 and under vs over 60), and stage of disease (IB vs IIA). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive PUVA comprising oral methoxsalen given 2 hours before whole body ultraviolet A therapy. PUVA is given 3 times per week.
• Arm II: Patients receive oral bexarotene once daily and PUVA as in arm I. In both arms, treatment repeats for up to 16 weeks in the absence of complete clinical response, disease progression, or unacceptable toxicity.

Patients are followed every 8 weeks until the first documented progression or relapse.

PROJECTED ACCRUAL: A total of 134 patients (67 per treatment arm) will be accrued for this study within 17 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed mycosis fungoides
• Stage IB or IIA
• Confirmed by current or prior diagnostic lesion biopsy

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2 times ULN
• Calcium no greater than 11.5 mg/dL

Cardiovascular

• No New York Heart Association grade III or IV cardiac insufficiency

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study participation* NOTE: *Women using hormonal contraception must also use a non-hormonal treatment
• Fasting triglycerides normal (prior antilipemic agents allowed to reach normalization)
• Willing and able to avoid prolonged exposure to the sun
• Willing to limit sun exposure on day of PUVA therapy
• No prior intolerance of or unresponsiveness to PUVA therapy
• No other prior or concurrent malignant tumor except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer
• No prior pancreatitis
• No other concurrent serious illness or infection that would preclude study participation
• No concurrent excessive alcohol consumption
• No photosensitivity due to intrinsic (e.g., lupus) or extrinsic (e.g., photosensitive drugs) factors
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• No known contraindications to study drug
• No known hypersensitivity to retinoids or hypervitaminosis A
• No uncontrolled diabetes mellitus
• No uncontrolled thyroid disease

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 3 months since prior interferon therapy

Chemotherapy

• No prior systemic combination chemotherapy
• No prior participation in another study of bexarotene
• At least 3 months since prior topical chemotherapy

Endocrine therapy

• At least 1 month since prior topical corticosteroids

Radiotherapy

• At least 6 months since prior total skin electron beam therapy
• At least 1 month since prior superficial radiotherapy

Surgery

• Not specified

Other

• At least 30 days since prior participation in another investigational drug study
• At least 3 months since prior photopheresis
• At least 1 month since prior UVB/PUVA phototherapy
• At least 1 month since prior retinoid class drugs
• At least 1 month since prior beta-carotene compounds
• At least 1 month since other prior topical medications (e.g., tar baths)
• No prior participation in this study
• No other concurrent anticancer therapy
• No other concurrent investigational drug therapy
• No concurrent drugs associated with pancreatic toxicity or known to increase triglyceride concentrations

Austria
      Allgemeines Krankenhaus der Stadt Wien, Vienna,  A-1090,  Austria; Recruiting
      Karl-Franzens-University Graz, Graz,  A-8010,  Austria; Recruiting
Belgium
      Universiteit Gent, Gent,  B-9000,  Belgium; Recruiting
Finland
      Helsinki University Central Hospital, Helsinki,  FIN-00029,  Finland; Recruiting
Germany
      Klinikum Minden, Minden,  D-32423,  Germany; Recruiting
Hungary
      Semmelweis University, Budapest,  1085,  Hungary; Recruiting
Israel
      Rabin Medical Center - Beilinson Campus, Petah-Tikva,  49100,  Israel; Recruiting
Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
Spain
      CSU Bellvitge - Hospital Princeps d'Espanya, Barcelona,  08907,  Spain; Recruiting
      Hospital Clinic de Barcelona, Barcelona,  08036,  Spain; Recruiting
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain; Recruiting
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain; Recruiting
Switzerland
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland; Recruiting
United Kingdom, England
      Guy's and St. Thomas' Hospitals NHS Foundation Trust, London,  England,  SE1 9RT,  United Kingdom; Recruiting
United Kingdom, Scotland
      Royal Infirmary of Edinburgh at Little France, Edinburgh,  Scotland,  EH16 4SA,  United Kingdom; Recruiting

Study chairs or principal investigators

Sean J. Whittaker, MD,  Guy's and St. Thomas' Hospitals NHS Foundation Trust   

Study ID Numbers:  CDR0000271933; EORTC-21011; NCT00056056
Record last reviewed:  March 2005
Last Updated:  March 15, 2005
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00056056
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08