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A Randomized Phase II Study of Oral Lenalidomide (Revlimid [TM]), an Antiangiogenic and Immunomodulatory Agent, in Subjects With Stage IV Ocular Melanoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Melanoma

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Trial Information

A Randomized Phase II Study of Oral Lenalidomide (Revlimid [TM]), an Antiangiogenic and Immunomodulatory Agent, in Subjects With Stage IV Ocular Melanoma


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).

Inclusion Criteria


-INCLUSION CRITERIA:

1. All patients with stage IV ocular melanoma, who have measurable disease will be
considered.

2. Patients must have histopathological documentation of ocular melanoma confirmed in
the Laboratory of Pathology/National Cancer Institute (NCI) of the Clinical Center at
the National Institutes of Health. This can be from tissue obtained outside the
National Institutes of Health (NIH).

3. Patient must be Eastern Cooperative Oncology Group (ECOG) performance status of less
than or equal to 2.

4. Patients must have a life expectancy of more than 3 months.

5. Hematological eligibility parameters (prescreen):

- Granulocyte count greater than 1,500/mm^3

- Platelet count greater than 100,000/mm^3

- If the creatinine is greater than 1.5 mg/dL, obtain a 24 hour urine collection.
Creatinine clearance must be greater than 60 mL/min/1.73m^2.

- Hepatic function: bilirubin (total) less than or equal to 2.0 mg/dl; Alanine
aminotransferase (ALT) less than 10 x upper limit of normal; Aspartate
aminotransferase (AST) less than 10 x upper limit of normal.

6. Patients must have recovered from any acute toxicity related to prior therapy or
surgery, to a grade 1 or less unless specified above.

7. 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.

8. Patients must not have an acute, critical illness, including a serious untreated
infection.

9. Patients must be willing to return to the National Institutes of Health (NIH) for
follow-up visits.

10. All patients who are sexually active and able to conceive will be required to use
contraception during treatment with lenalidomide.

Only two criteria are allowed by the Food and Drug Administration (FDA) for the status of
not of child bearing potential: hysterectomy or menopause for 24 consecutive months. Women
of child bearing potential will be required to use two methods of birth control, one
highly effective method and one additional method, at the same time during treatment and
for one month after the completion of lenalidomide treatment. These methods must be used
for at least four weeks before starting lenalidomide, during treatment, and for at least
four weeks following the last dose of lenalidomide. Acceptable forms of birth control
include:

Intrauterine device (IUD)

Latex condom

Hormonal (Birth control pills, injections, implants)

Diaphragm

Tubal Ligation

Cervical cap

Partner's vasectomy

Two barrier methods may be used if the physician agrees that the highly effective methods
are medically contraindicated.

Women of childbearing potential must have a negative urine pregnancy test 24 hours prior
to the start of lenalidomide.

Men who are sexually active must agree to use latex condoms.

Patients must be able to understand and sign informed consent form.

Patients must be greater than or equal to 18 years of age.

EXCLUSION CRITERIA:

1. 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.

2. 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.

3. 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.

4. 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.

5. Patients who have had prior therapy with lenalidomide.

6. Patients with known hypersensitivity reaction to lenalidomide.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Clinical Responses in Patients With Metastatic Ocular Melanoma

Outcome Description:

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.

Outcome Time Frame:

12 months

Safety Issue:

No

Principal Investigator

Steven K Libutti, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health

Authority:

United States: Federal Government

Study ID:

050095

NCT ID:

NCT00109005

Start Date:

April 2005

Completion Date:

April 2009

Related Keywords:

  • Melanoma
  • Response Rate
  • Toxicity
  • Progression-Free Survival
  • Overall Survival
  • Pharmacokinetic
  • Ocular Melanoma
  • Melanoma

Name

Location

National Cancer Institute (NCI)Bethesda, Maryland  20892