Ultraviolet Light Therapy Using Methoxsalen With or Without Bexarotene in Treating Patients With Mycosis Fungoides

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Determine if ultraviolet A light therapy with methoxsalen (PUVA) with or without bexarotene yields a significantly higher overall response rate in patients with mycosis fungoides. 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 145 patients will be accrued for this study within 25 months.

Official Title
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A Randomized, Open-Label Phase III Trial to Evaluate the Efficacy and Safety of Bexarotene (Targretin) Capsules Combined With PUVA, Compared to PUVA Treatment Alone in Patients With Mycosis Fungoides

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: bexarotene
* Drug: methoxypsoralen
* Procedure: UV light therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bexarotene and PUVA<br> | Drug: bexarotene<br>* The recommended initial dosage of Bexarotene (75 mg Bexarotene capsules to be administered according to body surface area) for patients entered in this trial is 300 mg/m2 /once a day, taken orally, till CCR, PD, unacceptable toxicity, 16 weeks of treatment, whichever comes first<br>Drug: methoxypsoralen<br>* The dose of methoxypsoralen, as conventional capsules or liquid-filled capsules, is based on the patient's weight. The standard dose of 0.6 mg/kg will be given to all patients three times weekly - Increasing dose of PUVA according to a set protocol after a Minimal Phototoxic Dose (MPD) testing.<br>Procedure: UV light therapy<br>* Initial UVA light exposure times should be based on the minimal phototoxic dose (MPD) for the specific light source being used. MPD can be determined by irradiating several skin areas 2 cm in diameter with varying light exposure times and determining the exposure time that produces erythema at 72 hours. The initial dose of UVA administered will be 70% of the MPD. The dose of UVA for the subsequent UVA sessions will be increased according to a standard protocol consisting of 20% increments with each successive treatment session depending on the presence of erythema.<br>|
| Active Comparator: PUVA<br> | Drug: methoxypsoralen<br>* The dose of methoxypsoralen, as conventional capsules or liquid-filled capsules, is based on the patient's weight. The standard dose of 0.6 mg/kg will be given to all patients three times weekly - Increasing dose of PUVA according to a set protocol after a Minimal Phototoxic Dose (MPD) testing.<br>Procedure: UV light therapy<br>* Initial UVA light exposure times should be based on the minimal phototoxic dose (MPD) for the specific light source being used. MPD can be determined by irradiating several skin areas 2 cm in diameter with varying light exposure times and determining the exposure time that produces erythema at 72 hours. The initial dose of UVA administered will be 70% of the MPD. The dose of UVA for the subsequent UVA sessions will be increased according to a standard protocol consisting of 20% increments with each successive treatment session depending on the presence of erythema.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (complete clinical response [CCR) and partial response [PR]) |  | 35 months after first patient in | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative dose of UVA required to achieve CCR |  | 35 months after first patient in | 
| Number of PUVA sessions necessary to achieve a CCR |  | 35 months after first patient in | 
| Duration of CCR as measured by Logrank every 4 weeks during treatment and then every 8 weeks until progression |  | 35 months after first patient in | 
| Time to relapse |  | 35 months after first patient in | 
| Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks |  | 35 months after first patient in | 
| Percentage of dropouts as measured by the percentage of cases not completing treatment due to toxicity at the completion of treatment |  | 35 months after first patient in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome