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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Terminated

CT.gov ID

NCT00056056

Collaborator

(none)

Enrollment

Locations

Arms

101

Duration (Months)

3.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: bexarotene Drug: methoxypsoralen Procedure: UV light therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

93 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2003

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bexarotene and PUVA	Drug: 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 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. Procedure: 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.
Active Comparator: PUVA	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. Procedure: 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.

Arm

Intervention/Treatment

Experimental: Bexarotene and PUVA

Drug: 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

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.

Procedure: 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.

Active Comparator: PUVA

Drug: methoxypsoralen

Procedure: UV light therapy

Outcome Measures

Primary Outcome Measures

Overall response rate (complete clinical response [CCR) and partial response [PR]) [35 months after first patient in]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Karl-Franzens-University Graz	Graz		Austria	A-8010
2	Allgemeines Krankenhaus - Universitatskliniken	Vienna		Austria	A-1090
3	Ghent University	Gent		Belgium	B-9000
4	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
5	Bispebjerg Hospital	Copenhagen		Denmark	2400
6	Helsinki University Central Hospital	Helsinki		Finland	FIN-00029
7	Centre Hospitalier Universitaire Henri Mondor	Creteil		France	94010
8	CHR Hotel Dieu	Nantes		France	44093
9	Klinikum der Stadt Mannheim	Mannheim		Germany	D-68135
10	Klinikum Minden	Minden		Germany	D-32423
11	Hospital Universitario Insular de Gran Canaria	Tuebingen		Germany	D-72076
12	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen		Germany	D-72076
13	Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg	Wuerzburg		Germany	D-
14	Semmelweis University	Budapest		Hungary	1085
15	County Hospital	Kaposvar		Hungary	H-7400
16	Rabin Medical Center - Beilinson Campus	Petah-Tikva		Israel	49100
17	Spedali Civili di Brescia	Brescia		Italy	25123
18	Istituto Dermopatico Dell' Immacolata	Rome		Italy	00167
19	Universita di Torino	Turin		Italy	10126
20	Leiden University Medical Center	Leiden		Netherlands	2300 CA
21	Hospital de la Santa Cruz i Sant Pau	Barcelona		Spain	08025
22	Hospital Clinic de Barcelona	Barcelona		Spain	08036
23	Hospital Universitari de Bellvitge	Barcelona		Spain	08907
24	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
25	Hospital Universitario Nuestra Senora de la Candelaria	Santa Cruz de Tenerife		Spain	38003
26	UniversitaetsSpital Zuerich	Zurich		Switzerland	CH-8091
27	St. Thomas' Hospital	London	England	United Kingdom	SE1 9RT
28	Royal Infirmary of Edinburgh at Little France	Edinburgh	Scotland	United Kingdom	EH16 4SA