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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT02068586
First received: February 19, 2014
Last updated: August 21, 2014
Last verified: August 2014
  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.


Condition Intervention Phase
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
Drug: Sunitinib
Drug: Valproic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase ll Study of Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Time of definitive treatment of the primary tumor until death from any cause, assessed at 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Tolerability [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Defined as the proportion of patients able to complete 6 months of treatment, including those who underwent dose reduction


Estimated Enrollment: 90
Study Start Date: March 2014
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sunitinib
Patients receive sunitinib malate PO daily for 6 months in the absence of disease progression or unacceptable toxicity
Drug: Sunitinib
Given PO
Other Names:
  • Sunitinib malate
  • Sutent
  • SU11248
Experimental: Valproic acid
Patients receive valproic acid PO daily for 6 months in the absence of disease progression or unacceptable toxicity
Drug: Valproic Acid
Given PO
Other Names:
  • VPA
  • Valproate
  • Valproate sodium
  • Depakote
  • Epilim
  • Valparin
  • Valpro
  • Stavzor

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02068586

Contacts
Contact: Takami Sato, MD 215-955-8874
Contact: Mary Ann Laudadio, RN 215-955-9980 MaryAnn.Laudadio@jefferson.edu

Locations
United States, Pennsylvania
Thomas Jefferson University Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Takami Sato, MD         
Contact: Mary Ann Laudadio, RN    215-955-9980    MaryAnn.Laudadio@jefferson.edu   
Sub-Investigator: Jianqing Lin, MD         
Sub-Investigator: Kendra Feeney, MD         
Sub-Investigator: Michael Mastrangelo, MD         
Sub-Investigator: Carol Shields, MD         
Sub-Investigator: Jerry Shields, MD         
Sponsors and Collaborators
Thomas Jefferson University
Pfizer
Investigators
Principal Investigator: Takami Sato, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT02068586     History of Changes
Other Study ID Numbers: 13P.377, 2013-047
Study First Received: February 19, 2014
Last Updated: August 21, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases
Sunitinib
Valproic Acid
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Anticonvulsants
Central Nervous System Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Antimanic Agents

ClinicalTrials.gov processed this record on September 18, 2014