Clinical Trials /

Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma

NCT02068586

Description:

This randomized phase II trial studies how well sunitinib malate or valproic acid works in preventing high-risk uveal (eye) melanoma from spreading to other parts of the body. Sunitinib malate may stop the transmission of growth signals into tumor cells and prevents these cells from growing. Valproic acid may change the expression of some genes in uveal melanoma and suppress tumor growth.

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma
  • Official Title: A Randomized Phase ll Study of Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 13P.377
  • SECONDARY ID: 2013-047
  • NCT ID: NCT02068586

Conditions

  • Ciliary Body and Choroid Melanoma, Medium/Large Size
  • Ciliary Body and Choroid Melanoma, Small Size
  • Iris Melanoma
  • Stage I Intraocular Melanoma
  • Stage IIA Intraocular Melanoma
  • Stage IIB Intraocular Melanoma
  • Stage IIIA Intraocular Melanoma
  • Stage IIIB Intraocular Melanoma
  • Stage IIIC Intraocular Melanoma

Interventions

DrugSynonymsArms
SunitinibSunitinib malate, Sutent, SU11248Sunitinib
Valproic AcidVPA, Valproate, Valproate sodium, Depakote, Epilim, Valparin, Valpro, StavzorValproic acid

Purpose

This randomized phase II trial studies how well sunitinib malate or valproic acid works in preventing high-risk uveal (eye) melanoma from spreading to other parts of the body. Sunitinib malate may stop the transmission of growth signals into tumor cells and prevents these cells from growing. Valproic acid may change the expression of some genes in uveal melanoma and suppress tumor growth.

Detailed Description

      PRIMARY OBJECTIVES:

      1) To assess the efficacy of adjuvant sunitinib malate or adjuvant valproic acid used for 6
      months to improve overall survival (OS) at 2 years in patients with high-risk uveal melanoma.

      SECONDARY OBJECTIVES:

        1. To assess the efficacy of adjuvant sunitinib malate and adjuvant valproic acid used for
           6 months in preventing the development of distal metastases (relapse-free survival, RFS)
           in patients with high-risk uveal melanoma.

        2. To confirm the safety and tolerability of 6 months of adjuvant sunitinib and adjuvant
           valproic acid in patients with high-risk uveal melanoma.

        3. To assess the quality of life during the adjuvant treatment.

      TERTIARY OBJECTIVES:

      1) To determine whether blood myeloid-derived suppressor cells (MDSCs) concentration and
      other inflammatory cytokines correlates with OS and RFS.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive sunitinib malate orally (PO) daily for 6 months in the absence of
      disease progression or unacceptable toxicity.

      ARM II: Patients receive valproic acid PO daily for 6 months in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      every 6 months for 3 years, and then annually thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
SunitinibExperimentalPatients receive sunitinib malate PO daily for 6 months in the absence of disease progression or unacceptable toxicity
  • Sunitinib
Valproic acidExperimentalPatients receive valproic acid PO daily for 6 months in the absence of disease progression or unacceptable toxicity
  • Valproic Acid

Eligibility Criteria

        Inclusion Criteria:

          1. Age >= 18 years old.

          2. Histologically-confirmed primary uveal melanoma.

          3. Definitive local treatment for primary tumor, including surgical resection
             (enucleation) or radiation therapy (radioactive plaque or external proton beam).

          4. High risk for distal recurrence defined as any of the following conditions: A) -
             Confirmed both monosomy 3 and 8q amplification; B) - Class II tumor.

          5. Less than 6 months from the date that local treatment (surgical or radiation) of the
             primary tumor was finalized.

          6. Karnofsky performance status (PS) scores of 70 or greater.

          7. If female, no pregnancy.

          8. If of child-bearing potential (< one year post-menopausal), must agree to practice an
             effective method of avoiding pregnancy (including oral or implanted contraceptives,
             intrauterine device, condom, diaphragm with spermicidal, cervical cap, abstinence or
             sterile sex partner) from the time informed consent is signed (women only) or the time
             of initiation of sunitinib (men only); both men and women must agree to continue using
             such precautions while receiving sunitinib or valproic acid and for 30 days after the
             final dose.

          9. Adequate organ function that has been determined within 2 weeks prior to the study
             entry, defined as:

               -  Absolute neutrophil count (ANC) ≥ 1500/mm3, platelets ≥ 100,000/mm3, and
                  hemoglobin ≥ 8 g/dl

               -  Serum creatinine < 1.5 times upper limit of normal range (ULN) or creatinine
                  clearance ≥ 40 ml/min

               -  Serum bilirubin < 1.5 times ULN and serum albumin > 2.0 g/dl

               -  Adequate cardiac function (EF> 50%) based on MUGA scan

        Exclusion Criteria:

          1. Other malignancy within 5 years, except curatively treated non-melanomatous skin
             cancer, curatively treated carcinoma in situ of the uterine cervix, or early stage
             (stage I or IIa) prostate cancer.

          2. Metastatic uveal melanoma.

          3. History of severe allergic reaction to sunitinib or valproic acid; inability to
             receive sunitinib or valproic acid.

          4. Previous treatment with sunitinib or valproic acid for uveal melanoma.

          5. Active treatment with valproic acid for non-oncological conditions, if this cannot be
             safely switched to an alternative agent.

          6. Active epilepsy or convulsive conditions that require continuous use of
             anticonvulsants.

          7. Patients with known urea cycle disorders (i.e.: ornithine transcarbamylase
             deficiency).

          8. Severe cardiovascular disease within 6 months, including myocardial infarction,
             severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic
             congestive heart failure, cerebro-vascular accident or transient ischemic attack,
             pulmonary embolism, life threatening arrhythmias, uncontrollable hypertension or QT
             prolongation syndrome.

          9. History of active liver disease (i.e. cirrhosis, viral or autoimmune hepatitis, etc.).

         10. Pregnancy or unwillingness to stop breast-feeding.

         11. Prior myelosuppressive chemotherapy or other investigational drug therapy within the
             last 6 months prior to initiation of sunitinib or valproic acid.

         12. Current evidence of hematemesis, melena or gross hematuria.

         13. History or presence of any significant bleeding disorders.

         14. Concurrent use of a strong CYP3A4 inhibitor or inducer (refer to Section 7). These
             medications should be discontinued or switched to a different medication with a weaker
             CYP3A4 interaction prior to enrollment into the study. If patients need to continue
             the same medication(s), they are excluded from the study.

         15. Chronic usage of aspirin greater than 81 mg/day.

         16. Unable to render informed consent and to follow protocol requirements.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:Time of definitive treatment of the primary tumor until death from any cause, assessed at 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Relapse-free survival
Time Frame:Time of definitive treatment of the primary tumor until confirmed metastatic relapse or death from any cause, assessed at 2 years
Safety Issue:
Description:
Measure:Tolerability
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of patients able to complete 6 months of treatment, including those who underwent dose reduction

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

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