A Study Comparing Temozolomide and Selumetinib for Treating Patients with Metastatic Melanoma of the Eye


About this study

The purpose of this study is to compare the effectiveness of temozolomide to selumetinib for the treatment of patients who have melanoma of the eye that has spread to other places in the body. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether temozolomide is more effective than selumetinib in treating melanoma of the eye.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • Must have histologically or cytologically confirmed metastatic uveal melanoma
    • If histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma
    • Pathologic confirmation of diagnosis will be performed at Memorial Sloan-Kettering Cancer Center (MSKCC) or at a participating site
  • Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral computed tomography (CT) scan
  • Life expectancy of greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count (ANC) ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Hemoglobin ≥ 9.0 g/dL (not requiring transfusions within the past 2 weeks)
  • Total bilirubin ≤ 1.5 times upper limit of normal
    • Hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 times upper limit of normal for  no concurrent liver metastases
  • AST(SGOT)/ALT(SGPT) ≤ 5 X institutional ULN for  concurrent liver metastases
  • Creatinine ≤ 1.5 mg/dL
  • Tumor Gnaq and Gna11 status must be determined on all using a Clinical Laboratory Improvement Act (CLIA) approved assay
    • If initial CLIA testing is performed locally, patients must consent to provide a tumor block or unstained slides to MSKCC for central review of Gnaq and Gna11 status
    • This central review may be performed retrospectively and will not delay treatment  study
  • Must agree to provide all imaging studies for central radiology review
    • This central radiology review may be performed retrospectively and will not be utilized for decision making for study
  • Ability to understand and the willingness to sign a written informed consent document
  • Eligibility for enrollment in each cohort is dependent upon tumor Gnaq/Gna11 status and prior therapy
    • Cohort 1, no prior TMZ or DTIC
      • Mutant Gnaq/Gna11 status
    • Cohort 2, no prior TMZ or DTIC
      • Wild-type Gnaq/Gna11 status
    • Cohort 3, received prior TMZ or DTIC
      • Mutant or wild-type Gnaq/Gna11 status
  • Every effort must be made to avoid administration of drugs that are inhibitors or inducers of cytochrome P450 1A2 (CYP1A2) and CYP3A4

Exclusion Criteria

  • Previously treated with a mitogen-activated protein kinase kinase (MEK) inhibitor
    • May have had any number of other prior therapies
      • At least 3 weeks must have elapsed since the last dose of systemic therapy
      • At least 6 weeks must have elapsed if the last regimen included carmustine (BCNU), mitomycin C or an anti-CTLA4 antibody
      • Must have experienced disease progression on prior therapy in the opinion of the treating investigator
  • Is receiving any other investigational agents
  • Has active or untreated brain metastases
    • Treated brain metastases must have been stable for at least 2 months
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to TMZ or DTIC or AZD6244
  • Uncontrolled intercurrent illness including, but not limited to
    • Ongoing or active infection or bleeding
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Unstable cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant 
    • Breast-feeding should be discontinued if the mother is treated with AZD6244
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Women of child-bearing potential must have a negative pregnancy test prior to entry
    • If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately
    • The AZD6244 manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle
  • Known human immunodeficiency virus (HIV)-positive and on combination antiretroviral therapy
    • Compensated HIV, with adequate cluster of differentiation (CD)4+ T-cell counts, and not requiring antiretroviral medication will be allowed
  • Taking vitamin E supplements while on study
  • Concomitant anti-cancer chemotherapy or other systemic drugs
    • Palliative radiation therapy will be allowed as long as all other eligibility criteria is met
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Corrected QT (QTc) interval > 450 msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions
  • Every effort must be made to avoid the use of a concomitant medication that can prolong the QTc interval while receiving AZD6244
    • If patient cannot discontinue medications that prolong the QTc interval while receiving AZD6244, close cardiac monitoring should be performed

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

J Quevedo, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office


More information


Publications are currently not available

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