Clinical trial NCT01007448: Study Evaluating Two Dose Levels of Targretin Capsules in Participants With Refractory Cutaneous T-Cell Lymphoma (CTCL)
Official title: Phase IV Randomized Study of Two Dose Levels of Targretin® Capsules in Subjects With Refractory Cutaneous T-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Refractory Cutaneous T-cell Lymphoma
Keywords: CTCL
bexarotene
Targretin
Refractory Cutaneous T-cell Lymphoma
cutaneous T-cell Lymphoma
MF
Mycoses fungoides
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2009-11-04
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, open-label, Phase IV study to assess the efficacy, tolerability, and safety of 2 initial dose levels of bexarotene capsules in participants with refractory CTCL.


Eligibility criteria: Inclusion Criteria:

1. A CTCL without central nervous system (CNS) involvement, confirmed by biopsy to be histologically consistent with CTCL diagnosis by a dermatopathologist.
2. Refractory to at least 1 systemic therapy for CTCL. (Refractory is defined as resistance to therapy due either to lack of response of at least 50% improvement or progression of disease while still on therapy after an initial response.)
3. Systemic therapy for CTCL is indicated.
4. A Karnofsky performance score ≥60%.
5. Age ≥18 years.
6. Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (ß-hCG) with a sensitivity of at least 50 milli-international units/liter (mIU/L) within 7 days prior to the initiation of treatment. Females of childbearing potential must have used simultaneously two highly effective methods of contraception (strongly recommended that 1 of the 2 forms of contraception be non-hormonal such as condom plus spermicide, condom plus diaphragm with spermicide, or have a vasectomized partner) or use an intrauterine device or must have been sexually abstinent for at least four weeks prior to or at least 1 menstrual cycle prior to (whichever is longer) the negative pregnancy test through entry in the study. Sexual abstinence or effective contraception must be used for at least 1 month prior to the initiation of therapy, during therapy, and for at least 1 month following discontinuation of therapy. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
7. Male participants with female partners of childbearing potential must agree to sexual abstinence or to practice 2 reliable forms of effective contraception used simultaneously (strongly recommended that 1 of the 2 forms of contraception be non-hormonal such as condom plus spermicide, condom plus diaphragm with spermicide, or partner with tubal ligation) or partner may use an intrauterine device, during the entire period of bexarotene capsule treatment and for at least 1 month after treatment is discontinued. Male participants with female sexual partners who are pregnant, possibly pregnant or who could become pregnant during the study must agree to use condoms during sexual intercourse during the entire period of bexarotene capsule treatment and for at least 1 month after the last dose of bexarotene capsules.
8. Must be willing and able to give informed consent and complete and understand, either oral or written, study procedures and assessments.
9. Participant must be suitable for participation in the study in the Investigator's opinion.
10. Fasting serum triglyceride within normal limits (\<150 mg/deciliter \[dL\]) prior to study entry.
11. Adequate renal function as evidenced by serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 milliliters (mL)/minute (min) as per the Cockroft and Gault formula.
12. Adequate hepatic function that is characterized by aspartate aminotransferase (SGOT \[AST\]), alanine aminotransferase (SGPT \[ALT\]), or serum bilirubin \<2.5 times the upper limit of normal.
13. Adequate bone marrow function as evidenced by hemoglobin ≥8 grams (g)/dL, absolute neutrophil count (ANC) ≥1,000/milliliters cubed (mm\^3), and platelets ≥50,000/mm\^3.

Exclusion Criteria

1. Cutaneous T-cell lymphoma involving the central nervous system.
2. Participants with known Human Immunodeficiency Virus (HIV) infection and active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection (HBV/HCV or HIV testing is not required for the purpose of this study).
3. Participation in any other investigational drug study within 30 days of entry in this study.
4. Within 5 years after the onset of menopause.
5. Received systemic corticosteroids within 6 months of entry in the study.
6. Known hypersensitivity to bexarotene or other component of bexarotene capsules.
7. Pregnancy, intent to become pregnant, or breast-feeding.
8. Received gemfibrozil within 1 day of starting the study.
9. Prior therapy for the treatment of CTCL:

   1. Psoralens and ultraviolet A light (PUVA) or ultraviolet B light (UVB) therapy within 3 weeks of study entry.
   2. Electron beam radiation therapy (EBT) or photopheresis within 3 weeks of study entry.
   3. Topical retinoids, nitrogen mustard, carmustine (BCNU), imiquimod, or other antipruritic medication within 2 weeks of study entry.

      If antipruritic medication cannot be avoided, antihistamine or antipruritic agents must be administered using a stable dose regimen for at least 1 week prior to initiation of study drug treatment and throughout the study, unless it is determined that a discontinuation or reduction in dose is indicated. Prior to the enrollment of any participant who will be taking systemic or dermatologically-applied antihistamine or anti-pruritic agent, the investigator must contact Eisai to discuss the need for such agent. Mineral oil, baby oil, and simple moisturizing lotions may be used as emollients. Low- to mid- potency topical corticosteroids are allowed only for participants with erythroderma (Stage III/IV CTCL) using a stable dose regimen for at least 4 weeks prior to study entry. High potency topical corticosteroids and tar baths are NOT permitted.

      NOTE: Prior to the enrollment of any participant who will be taking systemic or dermatologically-applied antihistamine or anti-pruritic agent, the Investigator must contact the Sponsor to discuss the need for such agent.
   4. Anticancer therapy of any kind (for example, methotrexate, cyclophosphamide, vorinostat, romidepsin, and interferon) within 30 days of entry to the study. Participant must recover from all signs of toxicity prior to entry in the study.
   5. Oral retinoid therapy for any indication within 3 months of study entry.
   6. Systemic therapy with Vitamin A in doses of greater than 15,000 International Units (IU) (5,000 microgram \[mcg\]) per day (equivalent to approximately 3 times Recommended Daily Allowance \[RDA\]) within 30 days of entry in this study.
10. Systemic antibiotic therapy within 2 weeks of entry in the study. (Participants with infections requiring antibiotics or likely to require antibiotics should be appropriately treated with a course of antibiotics terminating at least two weeks prior to entry, or if indicated, a chronic suppressive or prophylactic dose of antibiotics stabilized at least 2 weeks prior to entry. Participants who require initiation of or changes in antibiotic therapy during the study will not be considered a violation of the study protocol).
11. History of pancreatitis or significant risk factors for developing pancreatitis (for example, prior pancreatitis, uncontrolled hyperlipidemia, excessive alcohol consumption, uncontrolled diabetes mellitus, biliary tract disease, and medications known to increase triglyceride levels or to be associated with pancreatic toxicity).
12. Unwillingness or inability to minimize exposure to sunlight and artificial ultraviolet light while receiving bexarotene capsules.

Primary outcomes:
measure: Number of Participants With Tumor Response (Complete Response [CR], Clinical Complete Response [CCR], and Partial Response [PR]) in up to 5 Index Lesions as Determined by Investigator's Composite Assessment (CA) of Index Lesion Disease Severity
timeFrame: Baseline up to Week 24
measure: Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined by Physician's Global Assessment (PGA) of Clinical Condition
timeFrame: Baseline up to Week 24
measure: Number of Participants With Tumor Response of CR, CCR, PR, SD, and PD as Determined Percent Body Surface Area (BSA) Involvement
timeFrame: Baseline up to Week 24
Secondary outcomes:
measure: Duration of Tumor Response (CR, CCR, or PR) as Determined by Investigator's CA of Index Lesion Disease Severity
timeFrame: Baseline up to Week 24
measure: Duration of Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition
timeFrame: Baseline up to Week 24
measure: Duration of Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement
timeFrame: Baseline up to Week 24
measure: Time to Tumor Response (CR, CCR, or PR) as Determined by CA of Index Lesion Disease Severity
timeFrame: Baseline up to Week 24
measure: Time to Tumor Response (CR, CCR, or PR) as Determined by PGA of Clinical Condition
timeFrame: Baseline up to Week 24
measure: Time to Tumor Response (CR, CCR, or PR) as Determined by Percent BSA Involvement
timeFrame: Baseline up to Week 24
measure: Time to Tumor Progression as Determined by CA of Index Lesion Disease Severity
timeFrame: Baseline up to Week 24
measure: Time to Tumor Progression as Determined by PGA of Clinical Condition
timeFrame: Baseline up to Week 24
measure: Time to Tumor Progression as Determined by Percent BSA Involvement
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Miami
country: United States
facility: Florida Academic Dermatology Centers
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: New Orleans
country: United States
facility: Tulane
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals-Case Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute At the University of Utah
state: Utah
Study officials:
affiliation: Valeant Pharmaceutical NA
name: Mandeep Kaur, MD
role: STUDY_DIRECTOR
References: