Intraocular MelanomaPhase 2NCT00482911
Lenalidomide, Sunitinib, and Cyclophosphamide in Treating Patients With Stage IV Eye Melanoma
A Phase 2 study testing cyclophosphamide, lenalidomide and sunitinib malate in people with Intraocular Melanoma and Malignant Conjunctival Neoplasm, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intraocular Melanoma, Malignant Conjunctival Neoplasm
- What is being tested?
- cyclophosphamide, lenalidomide and sunitinib malate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Apr 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
About this study
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
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.
Read the 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.
- Being tested
- cyclophosphamide, lenalidomide, sunitinib malate
- Keywords
- recurrent intraocular melanoma, metastatic intraocular melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, conjunctival melanoma
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Also called cytoxan
25-50 mg by mouth once daily on days 1-28.
lenalidomideDrug
Also called revlimid
10 mg by mouth once daily on days 1-28.
sunitinib malateDrug
Also called sutent
12.5 - 25 mg by mouth once daily on days 1-28.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1-lenalidomide & cyclophosphamide | Experimental | 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). Receives: Drug: cyclophosphamide; Drug: lenalidomide |
| Cohort 2-sunitinib & cyclophosphamide | Experimental | 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). Receives: Drug: cyclophosphamide; Drug: sunitinib malate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Toxicity
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Measured: 16 months
Overall Survival
Time from date of on study to the date of death from any cause or last follow up
Measured: up to 16 months
Secondary outcomes (2)
Progression Free Survival
Proportion of patients who progress or die after the start of treatment
Measured: up to 16 months
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.
Measured: Baseline and end of treatment course 1 and 2, approximately 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2007 (estimated)
- Study startApr 2007
- Primary completionApr 2009
- Study completionApr 2009
Why it stopped: Investigator left the institute.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Intraocular MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Caryn Steakley, R.N., National Institutes of Health Clinical Center (CC)
- Investigators
- Steven K. Libutti, MD, Principal investigator, NCI - Surgery Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00482911
- Sponsor's protocol ID
- 070134
- Other IDs
- NCI-07-C-0134
- Status last verified
- Feb 2017
- First submitted
- 4 Jun 2007
- Last updated
- 27 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00482911
- Acronym / sponsor ID
- 070134
- Keywords
- recurrent intraocular melanoma, metastatic intraocular melanoma, ciliary body and choroid melanoma, medium/large size, extraocular extension melanoma, iris melanoma, conjunctival melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator left the institute.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2007 (actual)
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 5 Jun 2007 (estimated)
- Results
- Posted 14 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1-lenalidomide & cyclophosphamide | Experimental | Drug: cyclophosphamide, Drug: lenalidomideParticipants 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). |
| Cohort 2-sunitinib & cyclophosphamide | Experimental | Drug: cyclophosphamide, Drug: sunitinib malate2 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideAlso: cytoxan25-50 mg by mouth once daily on days 1-28. | Drug | Cohort 1-lenalidomide & cyclophosphamide, Cohort 2-sunitinib & cyclophosphamide |
| lenalidomideAlso: revlimid10 mg by mouth once daily on days 1-28. | Drug | Cohort 1-lenalidomide & cyclophosphamide |
| sunitinib malateAlso: sutent12.5 - 25 mg by mouth once daily on days 1-28. | Drug | Cohort 2-sunitinib & cyclophosphamide |
Primary outcome
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
2 secondary outcomes
Progression Free Survival
Time frame: up to 16 months
Changes in Gene Expression, Methylation and Protein Modification
Time frame: Baseline and end of treatment course 1 and 2, approximately 42 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven K. Libutti, MD principal investigator
NCI - Surgery Branch
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cyclophosphamide, lenalidomide and sunitinib malate in people with Intraocular Melanoma and Malignant Conjunctival Neoplasm, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (Complete and Partial Response) (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2017.