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

Primary Purpose

Lymphoma

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
bexarotene
methoxypsoralen
UV light therapy
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Karl-Franzens-University Graz
  • Allgemeines Krankenhaus - Universitatskliniken
  • Ghent University
  • U.Z. Gasthuisberg
  • Bispebjerg Hospital
  • Helsinki University Central Hospital
  • Centre Hospitalier Universitaire Henri Mondor
  • CHR Hotel Dieu
  • Klinikum der Stadt Mannheim
  • Klinikum Minden
  • Hospital Universitario Insular de Gran Canaria
  • Southwest German Cancer Center at Eberhard-Karls-University
  • Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
  • Semmelweis University
  • County Hospital
  • Rabin Medical Center - Beilinson Campus
  • Spedali Civili di Brescia
  • Istituto Dermopatico Dell' Immacolata
  • Universita di Torino
  • Leiden University Medical Center
  • Hospital de la Santa Cruz i Sant Pau
  • Hospital Clinic de Barcelona
  • Hospital Universitari de Bellvitge
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario Nuestra Senora de la Candelaria
  • UniversitaetsSpital Zuerich
  • St. Thomas' Hospital
  • Royal Infirmary of Edinburgh at Little France

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Bexarotene and PUVA

PUVA

Arm Description

Outcomes

Primary Outcome Measures

Overall response rate (complete clinical response [CCR) and partial response [PR])

Secondary Outcome Measures

Cumulative dose of UVA required to achieve CCR
Number of PUVA sessions necessary to achieve a CCR
Duration of CCR as measured by Logrank every 4 weeks during treatment and then every 8 weeks until progression
Time to relapse
Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks
Percentage of dropouts as measured by the percentage of cases not completing treatment due to toxicity at the completion of treatment

Full Information

First Posted
March 6, 2003
Last Updated
July 6, 2018
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00056056
Brief Title
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

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
January 2003 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
93 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bexarotene and PUVA
Arm Type
Experimental
Arm Title
PUVA
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
bexarotene
Intervention Description
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
Intervention Name(s)
methoxypsoralen
Intervention Description
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
Procedure
Intervention Name(s)
UV light therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall response rate (complete clinical response [CCR) and partial response [PR])
Time Frame
35 months after first patient in
Secondary Outcome Measure Information:
Title
Cumulative dose of UVA required to achieve CCR
Time Frame
35 months after first patient in
Title
Number of PUVA sessions necessary to achieve a CCR
Time Frame
35 months after first patient in
Title
Duration of CCR as measured by Logrank every 4 weeks during treatment and then every 8 weeks until progression
Time Frame
35 months after first patient in
Title
Time to relapse
Time Frame
35 months after first patient in
Title
Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks
Time Frame
35 months after first patient in
Title
Percentage of dropouts as measured by the percentage of cases not completing treatment due to toxicity at the completion of treatment
Time Frame
35 months after first patient in

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sean J. Whittaker, MD
Organizational Affiliation
St. Thomas' Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Karl-Franzens-University Graz
City
Graz
ZIP/Postal Code
A-8010
Country
Austria
Facility Name
Allgemeines Krankenhaus - Universitatskliniken
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Ghent University
City
Gent
ZIP/Postal Code
B-9000
Country
Belgium
Facility Name
U.Z. Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
FIN-00029
Country
Finland
Facility Name
Centre Hospitalier Universitaire Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
CHR Hotel Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Klinikum der Stadt Mannheim
City
Mannheim
ZIP/Postal Code
D-68135
Country
Germany
Facility Name
Klinikum Minden
City
Minden
ZIP/Postal Code
D-32423
Country
Germany
Facility Name
Hospital Universitario Insular de Gran Canaria
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Southwest German Cancer Center at Eberhard-Karls-University
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
City
Wuerzburg
ZIP/Postal Code
D-
Country
Germany
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1085
Country
Hungary
Facility Name
County Hospital
City
Kaposvar
ZIP/Postal Code
H-7400
Country
Hungary
Facility Name
Rabin Medical Center - Beilinson Campus
City
Petah-Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Spedali Civili di Brescia
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Istituto Dermopatico Dell' Immacolata
City
Rome
ZIP/Postal Code
00167
Country
Italy
Facility Name
Universita di Torino
City
Turin
ZIP/Postal Code
10126
Country
Italy
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 CA
Country
Netherlands
Facility Name
Hospital de la Santa Cruz i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Universitari de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario Nuestra Senora de la Candelaria
City
Santa Cruz de Tenerife
ZIP/Postal Code
38003
Country
Spain
Facility Name
UniversitaetsSpital Zuerich
City
Zurich
ZIP/Postal Code
CH-8091
Country
Switzerland
Facility Name
St. Thomas' Hospital
City
London
State/Province
England
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Royal Infirmary of Edinburgh at Little France
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH16 4SA
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
22924950
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.
Results Reference
derived

Learn more about this trial

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

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