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Lenalidomide, Sunitinib, and Cyclophosphamide in Treating Patients With Stage IV Eye Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00482911
Recruitment Status : Terminated (Investigator left the institute.)
First Posted : June 5, 2007
Results First Posted : November 14, 2012
Last Update Posted : March 27, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Caryn Steakley, R.N., National Institutes of Health Clinical Center (CC)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Intraocular Melanoma Malignant Conjunctival Neoplasm Drug: cyclophosphamide Drug: lenalidomide Drug: sunitinib malate Phase 2

Detailed Description:



  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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
Actual Study Start Date : April 2007
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Arm Intervention/treatment
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).
Drug: cyclophosphamide
25-50 mg by mouth once daily on days 1-28.
Other Name: cytoxan

Drug: 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).
Drug: cyclophosphamide
25-50 mg by mouth once daily on days 1-28.
Other Name: cytoxan

Drug: sunitinib malate
12.5 - 25 mg by mouth once daily on days 1-28.
Other Name: sutent

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: up to 16 months ]
    Proportion of patients who progress or die after the start of treatment

  2. 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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed ocular melanoma

    • Stage IV disease
  • Measurable disease
  • No active brain metastases

    • Patients with brain metastases must have had a complete excision or radiotherapy and remain asymptomatic with stable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan for ≥ 6 months


  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy > 3 months
  • Granulocyte count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
  • Bilirubin ≤ 2.0 mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 10 times upper limit of normal (ULN)
  • Prothrombin time (PT)/partial thromboplastin time (PTT)/International Normalized Ratio (INR) normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use one highly effective method of contraception (with an additional method) or barrier methods of contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy
  • Ejection fraction normal by echocardiogram
  • No acute, critical illness, including serious untreated infection
  • No history of any of the following:

    • Unstable or newly diagnosed angina pectoris
    • Myocardial infarction within the past 6 months
    • New York Heart Association class II-IV heart disease
    • Congestive heart failure
    • Chronic obstructive lung disease requiring oxygen therapy
    • Chronic uncontrollable hypertension
    • Uncontrolled seizure activity
  • No known human immunodeficiency virus (HIV) positivity
  • No known hypersensitivity reaction to thalidomide, lenalidomide, sunitinib malate, or cyclophosphamide


  • See Disease Characteristics
  • Recovered from all prior therapy
  • At least 4 weeks since prior surgery, chemotherapy (6 weeks for mitomycin C, nitrosoureas, or carboplatin), hormonal therapy, radiotherapy, or biological therapy
  • No concurrent grapefruit or grapefruit juice
  • No other concurrent antitumor therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00482911

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United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
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Principal Investigator: Steven K. Libutti, MD NCI - Surgery Branch

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Responsible Party: Caryn Steakley, R.N., Deputy Clinical Director, Center for Cancer Research, National Institutes of Health Clinical Center (CC) Identifier: NCT00482911     History of Changes
Other Study ID Numbers: 070134
First Posted: June 5, 2007    Key Record Dates
Results First Posted: November 14, 2012
Last Update Posted: March 27, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Caryn Steakley, R.N., National Institutes of Health Clinical Center (CC):
recurrent intraocular melanoma
metastatic intraocular melanoma
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
iris melanoma
conjunctival melanoma
Additional relevant MeSH terms:
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Conjunctival Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Conjunctival Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors