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

NCT ID: NCT00056056

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2011-06-30

Brief Summary

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

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.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bexarotene and PUVA

Group Type: EXPERIMENTAL

bexarotene

Intervention Type: DRUG

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

methoxypsoralen

Intervention Type: DRUG

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 therapy

Intervention Type: PROCEDURE

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.

PUVA

Group Type: ACTIVE_COMPARATOR

methoxypsoralen

Intervention Type: DRUG

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 therapy

Intervention Type: PROCEDURE

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.

Interventions

bexarotene

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

Intervention Type: DRUG

methoxypsoralen

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.

Intervention Type: DRUG

UV light therapy

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sean J. Whittaker, MD

Role: STUDY_CHAIR

St. Thomas' Hospital

Locations

Karl-Franzens-University Graz

Graz, , Austria

Allgemeines Krankenhaus - Universitatskliniken

Vienna, , Austria

Ghent University

Ghent, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Bispebjerg Hospital

Copenhagen, , Denmark

Helsinki University Central Hospital

Helsinki, , Finland

Centre Hospitalier Universitaire Henri Mondor

Créteil, , France

CHR Hotel Dieu

Nantes, , France

Klinikum der Stadt Mannheim

Mannheim, , Germany

Klinikum Minden

Minden, , Germany

Hospital Universitario Insular de Gran Canaria

Tübingen, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Semmelweis University

Budapest, , Hungary

County Hospital

Kaposvár, , Hungary

Rabin Medical Center - Beilinson Campus

Petah Tikva, , Israel

Spedali Civili di Brescia

Brescia, , Italy

Istituto Dermopatico Dell' Immacolata

Rome, , Italy

Universita di Torino

Turin, , Italy

Leiden University Medical Center

Leiden, , Netherlands

Hospital de la Santa Cruz i Sant Pau

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitari de Bellvitge

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, , Spain

UniversitaetsSpital Zuerich

Zurich, , Switzerland

St. Thomas' Hospital

London, England, United Kingdom

Royal Infirmary of Edinburgh at Little France

Edinburgh, Scotland, United Kingdom

Countries

Austria; Belgium; Denmark; Finland; France; Germany; Hungary; Israel; Italy; Netherlands; Spain; Switzerland; United Kingdom

References

Whittaker S, Ortiz P, Dummer R, Ranki A, Hasan B, Meulemans B, Gellrich S, Knobler R, Stadler R, Karrasch M. Efficacy and safety of bexarotene combined with psoralen-ultraviolet A (PUVA) compared with PUVA treatment alone in stage IB-IIA mycosis fungoides: final results from the EORTC Cutaneous Lymphoma Task Force phase III randomized clinical trial (NCT00056056). Br J Dermatol. 2012 Sep;167(3):678-87. doi: 10.1111/j.1365-2133.2012.11156.x.

Reference Type: DERIVED

PMID: 22924950 (View on PubMed)

Other Identifiers

2004-003701-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-21011

Identifier Type: -

Identifier Source: org_study_id