Clinical trial NCT00056056: Ultraviolet Light Therapy Using Methoxsalen With or Without Bexarotene in Treating Patients With Mycosis Fungoides
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lymphoma
Keywords: stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-03-07
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall response rate (complete clinical response [CCR) and partial response [PR])
timeFrame: 35 months after first patient in
Secondary outcomes:
measure: Cumulative dose of UVA required to achieve CCR
timeFrame: 35 months after first patient in
measure: Number of PUVA sessions necessary to achieve a CCR
timeFrame: 35 months after first patient in
measure: Duration of CCR as measured by Logrank every 4 weeks during treatment and then every 8 weeks until progression
timeFrame: 35 months after first patient in
measure: Time to relapse
timeFrame: 35 months after first patient in
measure: Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks
timeFrame: 35 months after first patient in
measure: Percentage of dropouts as measured by the percentage of cases not completing treatment due to toxicity at the completion of treatment
timeFrame: 35 months after first patient in
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Karl-Franzens-University Graz
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus - Universitatskliniken
city: Gent
country: Belgium
facility: Ghent University
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Nantes
country: France
facility: CHR Hotel Dieu
city: Mannheim
country: Germany
facility: Klinikum der Stadt Mannheim
city: Minden
country: Germany
facility: Klinikum Minden
city: Tuebingen
country: Germany
facility: Hospital Universitario Insular de Gran Canaria
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Wuerzburg
country: Germany
facility: Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Semmelweis University
city: Kaposvar
country: Hungary
facility: County Hospital
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Campus
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
city: Rome
country: Italy
facility: Istituto Dermopatico Dell' Immacolata
city: Turin
country: Italy
facility: Universita di Torino
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Senora de la Candelaria
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh at Little France
state: Scotland
Study officials:
affiliation: St. Thomas' Hospital
name: Sean J. Whittaker, MD
role: STUDY_CHAIR
References:
citation: 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.