Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02068586 |
Recruitment Status :
Active, not recruiting
First Posted : February 21, 2014
Last Update Posted : August 16, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | 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 |
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:
- 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.
- To confirm the safety and tolerability of 6 months of adjuvant sunitinib and adjuvant valproic acid in patients with high-risk uveal melanoma.
- 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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 150 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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 |
Actual Study Start Date : | November 19, 2014 |
Estimated Primary Completion Date : | December 31, 2022 |
Estimated Study Completion Date : | June 30, 2023 |

Arm | Intervention/treatment |
---|---|
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:
|
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:
|
- Overall survival [ Time Frame: Time of definitive treatment of the primary tumor until death from any cause, assessed at 2 years ]
- 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 ]
- Tolerability [ Time Frame: 6 months ]Defined as the proportion of patients able to complete 6 months of treatment, including those who underwent dose reduction

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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age >= 18 years old.
- Histologically-confirmed primary uveal melanoma.
- Definitive local treatment for primary tumor, including surgical resection (enucleation) or radiation therapy (radioactive plaque or external proton beam).
- High risk for distal recurrence defined as any of the following conditions: A) - Confirmed both monosomy 3 and 8q amplification; B) - Class II tumor.
- Less than 6 months from the date that local treatment (surgical or radiation) of the primary tumor was finalized.
- Karnofsky performance status (PS) scores of 70 or greater.
- If female, no pregnancy.
- 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.
-
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:
- 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.
- Metastatic uveal melanoma.
- History of severe allergic reaction to sunitinib or valproic acid; inability to receive sunitinib or valproic acid.
- Previous treatment with sunitinib or valproic acid for uveal melanoma.
- Active treatment with valproic acid for non-oncological conditions, if this cannot be safely switched to an alternative agent.
- Active epilepsy or convulsive conditions that require continuous use of anticonvulsants.
- Patients with known urea cycle disorders (i.e.: ornithine transcarbamylase deficiency).
- 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.
- History of active liver disease (i.e. cirrhosis, viral or autoimmune hepatitis, etc.).
- Pregnancy or unwillingness to stop breast-feeding.
- Prior myelosuppressive chemotherapy or other investigational drug therapy within the last 6 months prior to initiation of sunitinib or valproic acid.
- Current evidence of hematemesis, melena or gross hematuria.
- History or presence of any significant bleeding disorders.
- 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.
- Chronic usage of aspirin greater than 81 mg/day.
- Unable to render informed consent and to follow protocol requirements.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02068586
United States, Pennsylvania | |
Sidney Kimmel Cancer Center at Thomas Jefferson University | |
Philadelphia, Pennsylvania, United States, 19107 |
Principal Investigator: | Takami Sato, MD | Thomas Jefferson University |
Responsible Party: | Sidney Kimmel Cancer Center at Thomas Jefferson University |
ClinicalTrials.gov Identifier: | NCT02068586 |
Other Study ID Numbers: |
13P.377 2013-047 ( Other Identifier: CCRRC ) |
First Posted: | February 21, 2014 Key Record Dates |
Last Update Posted: | August 16, 2022 |
Last Verified: | August 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | Yes |
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 Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticonvulsants GABA Agents Neurotransmitter Agents Antimanic Agents Tranquilizing Agents Central Nervous System Depressants |