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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00056056
• Other study ID #: EORTC-21011
• Secondary ID: 2004-003701-24
• Status: Terminated
• Phase: Phase 3
• Start date: January 2003
• Est. completion date: June 2011

Study information

• Verified date: July 2018
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 93
• Est. completion date: June 2011
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Mycoses
• Mycosis Fungoides

Intervention

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
• 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.

Locations

Country	Name	City	State
Austria	Karl-Franzens-University Graz	Graz
Austria	Allgemeines Krankenhaus - Universitatskliniken	Vienna
Belgium	Ghent University	Gent
Belgium	U.Z. Gasthuisberg	Leuven
Denmark	Bispebjerg Hospital	Copenhagen
Finland	Helsinki University Central Hospital	Helsinki
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	CHR Hotel Dieu	Nantes
Germany	Klinikum der Stadt Mannheim	Mannheim
Germany	Klinikum Minden	Minden
Germany	Hospital Universitario Insular de Gran Canaria	Tuebingen
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Germany	Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg	Wuerzburg
Hungary	Semmelweis University	Budapest
Hungary	County Hospital	Kaposvar
Israel	Rabin Medical Center - Beilinson Campus	Petah-Tikva
Italy	Spedali Civili di Brescia	Brescia
Italy	Istituto Dermopatico Dell' Immacolata	Rome
Italy	Universita di Torino	Turin
Netherlands	Leiden University Medical Center	Leiden
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Cruz i Sant Pau	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
Switzerland	UniversitaetsSpital Zuerich	Zurich
United Kingdom	Royal Infirmary of Edinburgh at Little France	Edinburgh	Scotland
United Kingdom	St. Thomas' Hospital	London	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (complete clinical response [CCR) and partial response [PR])		35 months after first patient in
Secondary	Cumulative dose of UVA required to achieve CCR		35 months after first patient in
Secondary	Number of PUVA sessions necessary to achieve a CCR		35 months after first patient in
Secondary	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
Secondary	Time to relapse		35 months after first patient in
Secondary	Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks		35 months after first patient in
Secondary	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