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

Intraocular Melanoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00482911
• Other study ID #: 070134
• Secondary ID: NCI-07-C-0134
• Status: Terminated
• Phase: Phase 2
• First received: June 4, 2007
• Last updated: September 29, 2015
• Start date: April 2007
• Est. completion date: April 2009

Study information

• Verified date: November 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Conjunctival Neoplasms
• Intraocular Melanoma
• Malignant Conjunctival Neoplasm
• Melanoma
• Uveal Neoplasms

Intervention

Drug:
• cyclophosphamide
25-50 mg by mouth once daily on days 1-28.
• lenalidomide
10 mg by mouth once daily on days 1-28.
• sunitinib malate
12.5 - 25 mg by mouth once daily on days 1-28.

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate (Complete and Partial Response)	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 years	No
Primary	Toxicity	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.	16 months	Yes