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

This study has been terminated.
(poor accrual)
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00056056
First received: March 6, 2003
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Lymphoma
Drug: bexarotene
Drug: methoxypsoralen
Procedure: UV light therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Overall response rate (complete clinical response [CCR) and partial response [PR]) [ Time Frame: 35 months after first patient in ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cumulative dose of UVA required to achieve CCR [ Time Frame: 35 months after first patient in ] [ Designated as safety issue: No ]
  • Number of PUVA sessions necessary to achieve a CCR [ Time Frame: 35 months after first patient in ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to relapse [ Time Frame: 35 months after first patient in ] [ Designated as safety issue: No ]
  • Safety as assessed by CTC v2.0 every 4 weeks during treatment, then every 8 weeks [ Time Frame: 35 months after first patient in ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 93
Study Start Date: January 2003
Study Completion Date: June 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00056056

  Show 28 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Sean J. Whittaker, MD St. Thomas' Hospital
  More Information

No publications provided by European Organisation for Research and Treatment of Cancer - EORTC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00056056     History of Changes
Other Study ID Numbers: EORTC-21011, 2004-003701-24
Study First Received: March 6, 2003
Last Updated: June 19, 2012
Health Authority: Switzerland: Swissmedic
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
Israel: Israeli Health Ministry Pharmaceutical Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome

Additional relevant MeSH terms:
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bexarotene
Methoxsalen
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Photosensitizing Agents
Dermatologic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 22, 2014