Back to results

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

Primary Purpose

Intraocular Melanoma, Malignant Conjunctival Neoplasm

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

cyclophosphamide

lenalidomide

sunitinib malate

About this trial

This is an interventional treatment trial for Intraocular Melanoma focused on measuring recurrent intraocular melanoma, metastatic intraocular melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, conjunctival melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1-lenalidomide & cyclophosphamide

Cohort 2-sunitinib & cyclophosphamide

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Toxicity

Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Overall Survival

Time from date of on study to the date of death from any cause or last follow up

Secondary Outcome Measures

Progression Free Survival

Proportion of patients who progress or die after the start of treatment

Changes in Gene Expression, Methylation and Protein Modification

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.

Full Information

NCT ID

NCT00482911

First Posted

June 4, 2007

Last Updated

February 6, 2017

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00482911

Brief Title

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

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Terminated

Why Stopped

Investigator left the institute.

Study Start Date

April 2007 (Actual)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1-lenalidomide & cyclophosphamide

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2-sunitinib & cyclophosphamide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

cytoxan

Intervention Description

25-50 mg by mouth once daily on days 1-28.

Intervention Type

Drug

Intervention Name(s)

lenalidomide

Other Intervention Name(s)

revlimid

Intervention Description

10 mg by mouth once daily on days 1-28.

Intervention Type

Drug

Intervention Name(s)

sunitinib malate

Other Intervention Name(s)

sutent

Intervention Description

12.5 - 25 mg by mouth once daily on days 1-28.

Primary Outcome Measure Information:

Title

Response Rate (Complete and Partial Response)

Description

Time Frame

2 years

Title

Toxicity

Description

Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Time Frame

16 months

Title

Overall Survival

Description

Time from date of on study to the date of death from any cause or last follow up

Time Frame

up to 16 months

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

Proportion of patients who progress or die after the start of treatment

Time Frame

up to 16 months

Title

Changes in Gene Expression, Methylation and Protein Modification

Description

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.

Time Frame

Baseline and end of treatment course 1 and 2, approximately 42 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven K. Libutti, MD

Organizational Affiliation

NCI - Surgery Branch

Official's Role

Principal Investigator

Facility Information:

Facility Name

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892-1182

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs