LymphomaPhase 3NCT00056056
Ultraviolet Light Therapy Using Methoxsalen With or Without Bexarotene in Treating Patients With Mycosis Fungoides
A Phase 3 study testing bexarotene, methoxypsoralen and UV light therapy in people with Lymphoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 28 sites in 13 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- bexarotene, methoxypsoralen and UV light therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 28 sitesin 13 countries
- Study dates
- Jan 2003to Jun 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
28 sites in 13 countries.
28 sites in 13 countries
Germany5 sites
Klinikum der Stadt Mannheim
Mannheim, D-68135
Klinikum Minden
Minden, D-32423
Hospital Universitario Insular de Gran Canaria
Tübingen, D-72076
Southwest German Cancer Center at Eberhard-Karls-University
Tübingen, D-72076
Medizinische Klinik und Poliklinik II - Universitaetsklinikum Wuerzburg
Würzburg, D-
Spain5 sites
Hospital de la Santa Cruz i Sant Pau
Barcelona, 08025
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitari de Bellvitge
Barcelona, 08907
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Nuestra Senora de la Candelaria
Santa Cruz de Tenerife, 38003
Italy3 sites
Spedali Civili di Brescia
Brescia, 25123
Istituto Dermopatico Dell' Immacolata
Rome, 00167
Universita di Torino
Turin, 10126
Austria2 sites
Karl-Franzens-University Graz
Graz, A-8010
Allgemeines Krankenhaus - Universitatskliniken
Vienna, A-1090
France2 sites
Centre Hospitalier Universitaire Henri Mondor
Créteil, 94010
CHR Hotel Dieu
Nantes, 44093
Hungary2 sites
Semmelweis University
Budapest, 1085
County Hospital
Kaposvár, H-7400
United Kingdom2 sites
Royal Infirmary of Edinburgh at Little France
Edinburgh, Scotland, EH16 4SA
St. Thomas' Hospital
London, England, SE1 9RT
About this study
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
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.
Read the 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
- Being tested
- bexarotene, methoxypsoralen, UV light therapy
- Keywords
- stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome
- Medical subject headings
- Lymphoma, Mycosis Fungoides, Sezary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bexaroteneDrug
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
methoxypsoralenDrug
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 therapyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Bexarotene and PUVA | Experimental | Not described Receives: Drug: bexarotene; Drug: methoxypsoralen; Procedure: UV light therapy |
| PUVA | Active comparator | Not described Receives: Drug: methoxypsoralen; Procedure: UV light therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (complete clinical response [CCR) and partial response [PR])
Measured: 35 months after first patient in
Secondary outcomes (6)
Cumulative dose of UVA required to achieve CCR
Measured: 35 months after first patient in
Number of PUVA sessions necessary to achieve a CCR
Measured: 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
Measured: 35 months after first patient in
Time to relapse
Measured: 35 months after first patient in
Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks
Measured: 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
Measured: 35 months after first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2003 (estimated)
- Study startJan 2003
- Primary completionMay 2010
- Study completionJun 2011
Why it stopped: poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Sean J. Whittaker, MD, Study chair, St. Thomas' Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00056056
- Sponsor's protocol ID
- EORTC-21011
- Other IDs
- 2004-003701-24, 2004
- Status last verified
- Jul 2018
- First submitted
- 6 Mar 2003
- Last updated
- 9 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22924950
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00056056
- Acronym / sponsor ID
- EORTC-21011
- Conditions
- Lymphoma
- Keywords
- stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor accrual
- Enrolment
- 93 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Jan 2003
- Primary completion
- May 2010 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 7 Mar 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bexarotene and PUVA | Experimental | Drug: bexarotene, Drug: methoxypsoralen, Procedure: UV light therapy |
| PUVA | Active comparator | Drug: methoxypsoralen, Procedure: UV light therapy |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bexaroteneThe 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 | Bexarotene and PUVA |
| methoxypsoralenThe 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. | Drug | Bexarotene and PUVA, PUVA |
| UV light therapyInitial 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. | Procedure or surgery | Bexarotene and PUVA, PUVA |
Primary outcome
Overall response rate (complete clinical response [CCR) and partial response [PR])
Time frame: 35 months after first patient in
6 secondary outcomes
Cumulative dose of UVA required to achieve CCR
Time frame: 35 months after first patient in
Number of PUVA sessions necessary to achieve a CCR
Time frame: 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
Time frame: 35 months after first patient in
Time to relapse
Time frame: 35 months after first patient in
Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks
Time frame: 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
Time frame: 35 months after first patient in
Results and safety
The study was stopped early (reason given: poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Derived from this study: PubMed 22924950Whittaker 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.
Related trials for Lymphoma
RecruitingPhase 4
Efficacy and Safety of Polatuzumab Vedotin, Rituximab Combined With Reduced-dose Cyclophosphamide, Doxorubicin and Prednisone Regimen in the Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma: A Multicenter, Single-arm, Prospective Study
Diffuse Large B-Cell Lymphoma
Not yet recruitingPhase 1
huCART19-IL18-CD428z Cells for the Treatment of Patients With HIV With CD19+ Cancers
Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
Active, not recruitingPhase 2
Nivolumab, Ifosfamide, Carboplatin, and Etoposide as Second-Line Therapy in Treating Patients With Refractory or Relapsed HL
Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sean J. Whittaker, MD study chair
St. Thomas' Hospital
28 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bexarotene, methoxypsoralen and UV light therapy in people with Lymphoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 28 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Germany, Spain, Italy, Austria, Belgium and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: poor accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (complete clinical response [CCR) and partial response [PR]) (time frame: 35 months after first patient in). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00056056, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2018.