Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma

NCT02068586 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 13P.3772013-047JT 2437
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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; Stage I Uveal Melanoma AJCC V7; Stage II Uveal Melanoma AJCC V7; Stage III Uveal Melanoma AJCC V7; Ciliary Body and Choroid Melanoma, Medium/Large Size

Outcome Measures

Primary Outcomes (2)

• Overall survival (Cohort 1)

  OS distribution will be summarized using the method of Kaplan-Meier and the 2-year OS rate with two-sided 90% confidence interval (CI) will be provided. OS will be compared to the historic OS using a one-sample log-rank test.

  Time of definitive treatment of the primary tumor until death from any cause, assessed at 2 years

• Relapse-free survival (RFS) (Cohort 2 and 3)

  RFS distribution will be summarized using the method of Kaplan-Meier. 1.5-year, 2-year PFS rate will be computed with the corresponding two-sided 90% confidence intervals. OS and RFS will be compared to the null hypothesis OS or RFS using a one-sided one-sample Brookmeyer-Crowley test with alpha 0.05

  Time of definitive treatment of the primary tumor until confirmed metastatic relapse or death from any cause, assessed at 2 years

Secondary Outcomes (5)

• Relapse-free survival (Cohort 1)

  Time of definitive treatment of the primary tumor until confirmed metastatic relapse or death from any cause, assessed at 2 years

• Overall survival (Cohort 2)

  Time of definitive treatment of the primary tumor until death from any cause, assessed at 2 years

• Tolerability, defined as the proportion of patients able to complete 6 months of treatment, including those who underwent dose reduction

  6 months

• Incidence of toxicity assessed according to the National Institute of Health Common Terminology Criteria for Adverse Events (NIH CTCAE) version 4.0

  Up to 5 years

• Quality of life (QOL) assessed by Functional Assessment of Cancer Therapy-General (FACT-G) questionnaires

  Up to 6 months

Study Arms (4)

Sunitinib- (Cohort 1, Arm I)

EXPERIMENTAL

Patients receive sunitinib malate PO daily for 6 months in the absence of disease progression or unacceptable toxicity Quality-of-Life Assessment-Ancillary studies \- Laboratory Biomarker Analysis-Correlative studies

Drug: Sunitinib

Valproic acid- (Cohort 1, Arm II)

EXPERIMENTAL

Patients receive valproic acid PO daily for 6 months in the absence of disease progression or unacceptable toxicity Quality-of-Life Assessment-Ancillary studies Laboratory Biomarker Analysis-Correlative studies

Drug: Valproic Acid

Sunitinib Malate (Cohort 2)

EXPERIMENTAL

Patients receive sunitinib malate PO daily for 12 months in the absence of disease progression or unacceptable toxicity Quality-of-Life Assessment-Ancillary studies Laboratory Biomarker Analysis-Correlative studies

Drug: Sunitinib Malate

Sunitinib Malate + Valproic Acid (Cohort 3)

ACTIVE COMPARATOR

Patients receive sunitinib malate PO daily and valproic acid PO daily for 12 months in the absence of disease progression or unacceptable toxicity. Quality-of-Life Assessment-Ancillary studies Laboratory Biomarker Analysis-Correlative studies

Drug: Sunitinib Malate + Valproic Acid

Interventions

Sunitinib DRUG

Given PO

Also known as: Sunitinib malate, Sutent, SU11248, 341031-54-7 Butanedioic acid

Sunitinib- (Cohort 1, Arm I)

Valproic Acid DRUG

Given PO

Also known as: VPA, Valproate, Valproate sodium, Depakote, Epilim, Valparin, Valpro, Stavzor, Depakene, Di-n-propylacetic Acid

Valproic acid- (Cohort 1, Arm II)

Sunitinib Malate DRUG

Given PO

Also known as: sunitinib, Sutent, SU011248

Sunitinib Malate (Cohort 2)

Sunitinib Malate + Valproic Acid DRUG

Given PO

Also known as: Sunitinib Malate, sunitinib, Sutent, SU011248, Valproic Acid, VPA, Valproate, Valproate sodium, Depakote, Epilim, Valparin, Valpro, Stavzor, Depakene, Di-n-propylacetic Acid

Sunitinib Malate + Valproic Acid (Cohort 3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (sunitinib malate) (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
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelets \>= 100,000/mm\^3
• 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
• Serum albumin \> 2.0 g/dl
• Adequate cardiac function (ejection fraction \[EF\] \> 50%) based on multi gated acquisition (MUGA) scan or 2 dimensional-echocardiogram (2D-Echo)

You may not qualify if:

• 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
• 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 cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitor or inducer; 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

Sponsors & Collaborators

• Pfizer: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Sunitinib; Valproic Acid; Epilim

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Takami Sato, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2014
• First Posted: February 21, 2014
• Study Start: November 19, 2014
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)