Clinical trial NCT00109005
Conditions: Melanoma
Keywords: Response Rate Toxicity Progression-Free Survival Overall Survival Pharmacokinetic Ocular Melanoma
Sponsor: National Cancer Institute (NCI)
Start date: 2005-04-01; Completion date: 2009-04-01
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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).

Arms: arm 1: oral dose (1 capsule) lenalidomide 25 mg per day 7 days a week for 3 weeks arm 2: oral dose (1 capsule) lenalidomide 5 mg per day 7 days a week for 3 weeks
Interventions: intervention 1: Revlimid
Intervention descriptions: intervention 1: 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

Protocol documents: