MelanomaPhase 2NCT00109005
Lenalidomide (Revlimid) to Treat Advanced Ocular Melanoma
A Phase 2 study testing Revlimid in people with Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will test whether an experimental drug called Revlimid (lenalidomide) can reduce tumor size and prolong survival in patients with metastatic melanoma (melanoma that has spread beyond the original tumor site). It will also examine the toxicity and blood effects of Revlimid. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Revlimid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to 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
Who may be able to join
None listed.
Who cannot join
- Patients with evidence of active brain metastases will be excluded. Patients must have had a complete excision or radiotherapy and remain asymptomatic with stable disease as shown by magnetic resonance imaging (MRI) for at least six months.
- Patients who are pregnant or lactating. No data is currently available about the excretion of lenalidomide in breast milk. Although no preclinical data suggest teratogenicity with this compound, because of the relationship to thalidomide, we will exclude patients who are pregnant or lactating.
- Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York class II-IV congestive heart failure, chronic obstructive lung disease requiring oxygen therapy or uncontrolled seizure activity are not eligible.
- Patients who are known positive for human immunodeficiency virus (HIV) as it may increase their risk of infection since lenalidomide has effects on cells involved in the immune system.
- Patients who have had prior therapy with lenalidomide.
- Patients with known hypersensitivity reaction to lenalidomide.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Official title: A Randomized Phase II Study of Oral Lenalidomide (Revlimid [TM]), an Antiangiogenic and Immunomodulatory Agent, in Subjects With Stage IV Ocular Melanoma
This study will test whether an experimental drug called Revlimid (lenalidomide) can reduce tumor size and prolong survival in patients with metastatic melanoma (melanoma that has spread beyond the original tumor site). It will also examine the toxicity and blood effects of Revlimid.
Patients 18 years of age and older with stage IV ocular melanoma may be eligible for this study. Candidates are screened with a medical history and physical and examination, blood and urine tests, electrocardiogram, chest x-ray, computed tomography (CT) scan and other imaging scans if needed, such as a bone scan, magnetic resonance imaging (MRI), ultrasound, or positron emission tomography (PET).
Read more
Participants are admitted to the National Institutes of Health (NIH) Clinical Center for 24 hours for their first oral dose of Revlimid. During the hospital stay, blood is drawn before the dose is given and again at 0.25, 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after dosing to see how the body handles the drug. If the drug is well tolerated, patients are sent home with a 21-day supply of drug to take once a day for 21 days, then go off drug 7 days. This regimen constitutes one 28-day treatment cycle. Treatment cycles may continue for up to 2 years.
Patients keep a daily diary of side effects and have blood drawn once a week. The drug dose may be adjusted according to the laboratory test results. If unacceptable toxicity occurs, treatment may be stopped.
Patients who agree to be biopsied undergo this procedure before treatment begins and at the end of treatment cycles 3 and 6. A small area of skin is numbed with medicine and a small piece of tumor is removed with a needle or by a small cut in the tumor. The tissue is examined under a microscope.
Patients return to NIH after the first month of treatment and then every 3 months to evaluate their tumors and treatment of side effects. The visits include a physical examination, x-rays and scans to evaluate tumors. Visits are scheduled every 3 months while on treatment; then every 3 months for 2 years afterwards; then every 4 months for 1 year; and as needed after that. Patients will have a brain magnetic resonance imaging scan once a year to watch for new tumor areas.
Read the detailed description
Background:
- Patients with stage IV ocular melanoma have very few available treatment options and an overall poor prognosis.
- Pre-clinical and early clinical evidence suggest that lenalidomide has activity against solid tumors.
- This trial is designed to evaluate the safety and efficacy of two different doses of a novel antiangiogenic and immunomodulatory agent, lenalidomide (Revlimid ).
Objectives:
Primary Objectives:
- Determine the response rate to lenalidomide at two dose levels for patients with Stage IV ocular melanoma.
- To determine the toxicity of lenalidomide at two dose levels in this setting.
Secondary Objectives:
- To determine the progression free and overall survival of patients with Stage IV ocular melanoma treated with lenalidomide.
- When easily accessible, obtain tissue at baseline and during therapy to evaluate the effects of these agents on pathways, thought to be modulated by lenalidomide in pre-clinical studies.
- To determine the pharmacokinetics of lenalidomide at these two doses in patients with Stage IV ocular melanoma.
- To determine if there is a dose level with potentially superior efficacy and acceptable toxicity.
Eligibility:
- Patients > 18 years of age with stage IV ocular melanoma, who have measurable disease.
- Patient must be Eastern Cooperative Oncology Group (ECOG) performance status of = 2 and a life expectancy of more than 3 months.
- Patients must have adequate organ function.
- Patients must not have had prior surgery, chemotherapy, hormonal therapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study medication.
- Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy.
- Patients must not have an acute, critical illness,.
- All patients who are sexually active and able to conceive will be required to use contraception during treatment with lenalidomide
Design:
- A phase II trial in which patients are randomized to 2 dose levels of lenalidomide administered for 21 days every 28 days for 2 years.
- 76 patients (allowing for up to 3 inevaluable patients per dose level) will be enrolled over 4 to 5 years.
- The objective of the trial will be to determine in each of the two groups of patients (5 mg and 25 mg dose levels) whether, CC5013 is able to be associated with a response rate (partial response (PR) + complete response (CR)) that can rule out 10% (p0=0.10) in favor of an improved response rate of 30% (p1=0.30).
- Conditions
- Melanoma
- Being tested
- Revlimid
- Keywords
- Response Rate, Toxicity, Progression-Free Survival, Overall Survival, Pharmacokinetic, Ocular Melanoma
- Medical subject headings
- Melanoma, Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RevlimidDrug
Also called Lenalidomide
oral dose (1 capsule) 25 mg per day 7 days a week for cohort 1 oral dose (1 capsule) 5 mg per day 7 days a week for cohort 2
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - 25 mg lenalidomide (Revlimid) | Experimental | oral dose (1 capsule) lenalidomide 25 mg per day 7 days a week for 3 weeks Receives: Drug: Revlimid |
| Cohort 2 - 5 mg lenalidomide (Revlimid) | Experimental | oral dose (1 capsule) lenalidomide 5 mg per day 7 days a week for 3 weeks Receives: Drug: Revlimid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Responses in Patients With Metastatic Ocular Melanoma
Clinical response is assessed by the Response Evaluation Criteria for Adverse Events in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: 12 months
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Measured: 24 months
Secondary outcomes (5)
Progression Free Survival
Time interval from start of treatment to documented evidence of disease progression.
Measured: up to 2 years
Overall Survival
Date of on-study to the date of death from any cause or last follow up.
Measured: up to 2 years
Determine Pharmacokinetics of Lenalidomide at Two Dose Levels: 5 mg and 25 mg
Plasma samples will be obtained and plasma concentrations will be determined by a reversed-phase high-performance liquid chromatography (HPLC) assay using mass spectrometry (MS) detection.
Measured: Prior to treatment on cycle 1, day 1 and then on cycle 1, day 1 at 0.25, 0.5, 1, 2, 4, 6, 9 and 12 hours. Cycle 1, day 2 at 24 hours.
Determine Dose Level With Superior Efficacy and Acceptable Toxicity
The most efficacious dose (with greater number of responses) with acceptable toxicity profile will be considered for use in subsequent trials. iI the number of responses is tied, then toxicity criteria (Common Terminology criteria (CTC) v3.0) will be used to select the preferred dose.
Measured: up to 2 years
Evaluate Effects of Lenalidomide on Pathways
Tissue will be obtained to evaluate the effects of lenalidomide on pathways thought to be modulated by lenalidomide.
Measured: Baseline and at the end of treatment cycles 3 and 6. Every 21 day supply of lenalidomide with a 7 day rest (total of 28 days) will be considered a cycle of therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2005 (estimated)
- Study startApr 2005
- Primary completionApr 2009
- Study completionApr 2009
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Caryn Steakley, R.N., National Institutes of Health Clinical Center (CC)
- Investigators
- Caryn Steakley, Principal investigator, National Cancer Institute, National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00109005
- Sponsor's protocol ID
- 050095
- Other IDs
- 05-C-0095
- Status last verified
- Nov 2016
- First submitted
- 21 Apr 2005
- Last updated
- 2 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Gragoudas ES, Egan KM, Seddon JM, Glynn RJ, Walsh SM, Finn SM, Munzenrider JE, Spar MD. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991 Mar;98(3):383-9; discussion 390. doi: 10.1016/s0161-6420(91)32285-1.
PubMed 2023760
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Oral Lenalidomide (Revlimid [TM]), an Antiangiogenic and Immunomodulatory Agent, in Subjects With Stage IV Ocular Melanoma
- ClinicalTrials.gov ID
- NCT00109005
- Acronym / sponsor ID
- 050095
- Conditions
- Melanoma
- Keywords
- Response Rate, Toxicity, Progression-Free Survival, Overall Survival, Pharmacokinetic, Ocular Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2005
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 22 Apr 2005 (estimated)
- Results
- Posted 30 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test whether an experimental drug called Revlimid (lenalidomide) can reduce tumor size and prolong survival in patients with metastatic melanoma (melanoma that has spread beyond the original tumor site). It will also examine the toxicity and blood effects of Revlimid.
Patients 18 years of age and older with stage IV ocular melanoma may be eligible for this study. Candidates are screened with a medical history and physical and examination, blood and urine tests, electrocardiogram, chest x-ray, computed tomography (CT) scan and other imaging scans if needed, such as a bone scan, magnetic resonance imaging (MRI), ultrasound, or positron emission tomography (PET).
Participants are admitted to the National Institutes of Health (NIH) Clinical Center for 24 hours for their first oral dose of Revlimid. During the hospital stay, blood is drawn before the dose is given and again at 0.25, 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after dosing to see how the body handles the drug. If the drug is well tolerated, patients are sent home with a 21-day supply of drug to take once a day for 21 days, then go off drug 7 days. This regimen constitutes one 28-day treatment cycle. Treatment cycles may continue for up to 2 years.
Patients keep a daily diary of side effects and have blood drawn once a week. The drug dose may be adjusted according to the laboratory test results. If unacceptable toxicity occurs, treatment may be stopped.
Patients who agree to be biopsied undergo this procedure before treatment begins and at the end of treatment cycles 3 and 6. A small area of skin is numbed with medicine and a small piece of tumor is removed with a needle or by a small cut in the tumor. The tissue is examined under a microscope.
Patients return to NIH after the first month of treatment and then every 3 months to evaluate their tumors and treatment of side effects. The visits include a physical examination, x-rays and scans to evaluate tumors. Visits are scheduled every 3 months while on treatment; then every 3 months for 2 years afterwards; then every 4 months for 1 year; and as needed after that. Patients will have a brain magnetic resonance imaging scan once a year to watch for new tumor areas.
Detailed description
Background:
- Patients with stage IV ocular melanoma have very few available treatment options and an overall poor prognosis.
- Pre-clinical and early clinical evidence suggest that lenalidomide has activity against solid tumors.
- This trial is designed to evaluate the safety and efficacy of two different doses of a novel antiangiogenic and immunomodulatory agent, lenalidomide (Revlimid ).
Objectives:
Primary Objectives:
- Determine the response rate to lenalidomide at two dose levels for patients with Stage IV ocular melanoma.
- To determine the toxicity of lenalidomide at two dose levels in this setting.
Secondary Objectives:
- To determine the progression free and overall survival of patients with Stage IV ocular melanoma treated with lenalidomide.
- When easily accessible, obtain tissue at baseline and during therapy to evaluate the effects of these agents on pathways, thought to be modulated by lenalidomide in pre-clinical studies.
- To determine the pharmacokinetics of lenalidomide at these two doses in patients with Stage IV ocular melanoma.
- To determine if there is a dose level with potentially superior efficacy and acceptable toxicity.
Eligibility:
- Patients > 18 years of age with stage IV ocular melanoma, who have measurable disease.
- Patient must be Eastern Cooperative Oncology Group (ECOG) performance status of = 2 and a life expectancy of more than 3 months.
- Patients must have adequate organ function.
- Patients must not have had prior surgery, chemotherapy, hormonal therapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study medication.
- Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy.
- Patients must not have an acute, critical illness,.
- All patients who are sexually active and able to conceive will be required to use contraception during treatment with lenalidomide
Design:
- A phase II trial in which patients are randomized to 2 dose levels of lenalidomide administered for 21 days every 28 days for 2 years.
- 76 patients (allowing for up to 3 inevaluable patients per dose level) will be enrolled over 4 to 5 years.
- The objective of the trial will be to determine in each of the two groups of patients (5 mg and 25 mg dose levels) whether, CC5013 is able to be associated with a response rate (partial response (PR) + complete response (CR)) that can rule out 10% (p0=0.10) in favor of an improved response rate of 30% (p1=0.30).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - 25 mg lenalidomide (Revlimid) | Experimental | Drug: Revlimidoral dose (1 capsule) lenalidomide 25 mg per day 7 days a week for 3 weeks |
| Cohort 2 - 5 mg lenalidomide (Revlimid) | Experimental | Drug: Revlimidoral dose (1 capsule) lenalidomide 5 mg per day 7 days a week for 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- Patients with evidence of active brain metastases will be excluded. Patients must have had a complete excision or radiotherapy and remain asymptomatic with stable disease as shown by magnetic resonance imaging (MRI) for at least six months.
- Patients who are pregnant or lactating. No data is currently available about the excretion of lenalidomide in breast milk. Although no preclinical data suggest teratogenicity with this compound, because of the relationship to thalidomide, we will exclude patients who are pregnant or lactating.
- Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York class II-IV congestive heart failure, chronic obstructive lung disease requiring oxygen therapy or uncontrolled seizure activity are not eligible.
- Patients who are known positive for human immunodeficiency virus (HIV) as it may increase their risk of infection since lenalidomide has effects on cells involved in the immune system.
- Patients who have had prior therapy with lenalidomide.
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 |
|---|---|---|
| RevlimidAlso: Lenalidomideoral dose (1 capsule) 25 mg per day 7 days a week for cohort 1 oral dose (1 capsule) 5 mg per day 7 days a week for cohort 2 | Drug | Cohort 1 - 25 mg lenalidomide (Revlimid), Cohort 2 - 5 mg lenalidomide (Revlimid) |
Primary outcome
Clinical Responses in Patients With Metastatic Ocular Melanoma
Time frame: 12 months
Clinical response is assessed by the Response Evaluation Criteria for Adverse Events in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Number of Participants With Adverse Events
Time frame: 24 months
Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
5 secondary outcomes
Progression Free Survival
Time frame: up to 2 years
Overall Survival
Time frame: up to 2 years
Determine Pharmacokinetics of Lenalidomide at Two Dose Levels: 5 mg and 25 mg
Time frame: Prior to treatment on cycle 1, day 1 and then on cycle 1, day 1 at 0.25, 0.5, 1, 2, 4, 6, 9 and 12 hours. Cycle 1, day 2 at 24 hours.
Determine Dose Level With Superior Efficacy and Acceptable Toxicity
Time frame: up to 2 years
Evaluate Effects of Lenalidomide on Pathways
Time frame: Baseline and at the end of treatment cycles 3 and 6. Every 21 day supply of lenalidomide with a 7 day rest (total of 28 days) will be considered a cycle of therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2023760Gragoudas ES, Egan KM, Seddon JM, Glynn RJ, Walsh SM, Finn SM, Munzenrider JE, Spar MD. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991 Mar;98(3):383-9; discussion 390. doi: 10.1016/s0161-6420(91)32285-1.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
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.
Caryn Steakley principal investigator
National Cancer Institute, National Institutes of Health
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 Revlimid in people with Melanoma, run by National Cancer Institute (NCI) 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?
The sponsor lists 0 inclusion and 6 exclusion criteria. 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: finished, as of the sponsor's last update on 2 Jan 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 30 Oct 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?
Clinical Responses in Patients With Metastatic Ocular Melanoma (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00109005, which also lists 1 linked publication.
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 2 Jan 2017.