Lenalidomide, Sunitinib, and Cyclophosphamide in Treating Patients With Stage IV Eye Melanoma
RATIONALE: Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with sunitinib and low doses of cyclophosphamide once a day may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving lenalidomide together with sunitinib and cyclophosphamide works in treating patients with stage IV eye melanoma.
|Intraocular Melanoma Malignant Conjunctival Neoplasm||Drug: cyclophosphamide Drug: lenalidomide Drug: sunitinib malate||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Combination Oral CC-5013 Lenalidomide (Revlimid™), Oral Sunitinib (Sutent™) and Low Dose Oral Metronomic Cyclophosphamide for the Treatment of Stage IV Ocular Melanoma|
- Response Rate (Complete and Partial Response) [ Time Frame: 2 years ]Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
- Toxicity [ Time Frame: 16 months ]Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
- Overall Survival [ Time Frame: up to 16 months ]Time from date of on study to the date of death from any cause or last follow up
- Progression Free Survival [ Time Frame: up to 16 months ]Proportion of patients who progress or die after the start of treatment
- Changes in Gene Expression, Methylation and Protein Modification [ Time Frame: Baseline and end of treatment course 1 and 2, approximately 42 days ]Ribonucleic acid (RNA), deoxyribonucleic acid (DNA) and protein obtained from blood, urine and/or tissue was to be evaluated for changes in gene expression, methylation and/or protein modification.
|Actual Study Start Date:||April 2007|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Experimental: Cohort 1-lenalidomide & cyclophosphamide
Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).
25-50 mg by mouth once daily on days 1-28.
Other Name: cytoxanDrug: lenalidomide
10 mg by mouth once daily on days 1-28.
Other Name: revlimid
Experimental: Cohort 2-sunitinib & cyclophosphamide
2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).
25-50 mg by mouth once daily on days 1-28.
Other Name: cytoxanDrug: sunitinib malate
12.5 - 25 mg by mouth once daily on days 1-28.
Other Name: sutent
- Determine the response rate in patients with stage IV ocular melanoma treated with lenalidomide, sunitinib malate, and low-dose metronomic cyclophosphamide.
- Determine the toxicity of this regimen in these patients.
- Determine the progression-free survival of patients treated with this regimen.
- Obtain blood, urine, and tissue samples from these patients, when easily accessible, to determine the effects of this regimen on pathways thought to have been modulated by this regimen in pre-clinical studies.
OUTLINE: This is nonrandomized, uncontrolled, open-label study.
Patients receive oral lenalidomide, oral sunitinib malate*, and oral low-dose cyclophosphamide once daily on days 1-28. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
NOTE: *Some patients will not receive sunitinib malate during course 1.
After completion of study treatment, patients are followed every 3 months for 2 years, every 4 months for 3 years and then annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00482911
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Principal Investigator:||Steven K. Libutti, MD||NCI - Surgery Branch|