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

Phase 3TerminatedNCT00056056

European Organisation for Research and Treatment of Cancer - EORTC93 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lymphoma

Interventions

bexaroteneDRUG

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

methoxypsoralenDRUG

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.

UV light therapyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (28)

Karl-Franzens-University Graz