Clinical trial NCT00482911: Lenalidomide, Sunitinib, and Cyclophosphamide in Treating Patients With Stage IV Eye Melanoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Intraocular Melanoma
Malignant Conjunctival Neoplasm
Keywords: recurrent intraocular melanoma
metastatic intraocular melanoma
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
iris melanoma
conjunctival melanoma
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-06-05
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: OBJECTIVES:

Primary

* Determine the response rate in patients with stage IV ocular melanoma treated with lenalidomide, sunitinib malate, and low-dose metronomic cyclophosphamide.

Secondary

* 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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

* 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

PRIOR CONCURRENT THERAPY:

* 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

Primary outcomes:
measure: Response Rate (Complete and Partial Response)
timeFrame: 2 years
measure: Toxicity
timeFrame: 16 months
measure: Overall Survival
timeFrame: up to 16 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: up to 16 months
measure: Changes in Gene Expression, Methylation and Protein Modification
timeFrame: Baseline and end of treatment course 1 and 2, approximately 42 days
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
state: Maryland
Study officials:
affiliation: NCI - Surgery Branch
name: Steven K. Libutti, MD
role: PRINCIPAL_INVESTIGATOR
References: