Ciliary Body and Choroid Melanoma, Medium/Large SizePhase 2NCT02068586

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

A Phase 2 study testing Sunitinib, Valproic Acid and Sunitinib Malate in people with Ciliary Body and Choroid Melanoma, Medium/Large Size and Ciliary Body and Choroid Melanoma, Small Size, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Iris Melanoma
What is being tested?: Sunitinib, Valproic Acid and Sunitinib Malate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 210 participants
Where: 1 siteUnited States
Study dates: 19 Nov 2014to 31 Dec 2027
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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)
Life expectancy of at least 5 years

Who cannot join

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

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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
Unable to render informed consent and to follow protocol requirements
Any other medical condition(s) that, at the discretion of the principal investigator (PI), would make the patient inappropriate for this study

Trial locations and contacts

1 site in 1 country.

United States1 site

Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

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

Read the detailed description

PRIMARY OBJECTIVES:

To assess the efficacy of adjuvant sunitinib malatate (sunitinib) and adjuvant valproic acid used for 6 months to improve overall survival (OS) at 2 years in patients with high risk uveal melanoma. (Cohort 1) II. To assess the efficacy of adjuvant sunitinib used for 12 months to improve 1.5-year relapse free survival (RFS) in patients with high-risk uveal melanoma. (Cohort 2) III. To assess whether the combination of sunitinib and valproic acid used for 12 months improve the 2-year relapse free survival (RFS) in patients with high-risk uveal melanoma. (Cohort 3)

SECONDARY OBJECTIVES:

To assess the efficacy of adjuvant sunitinib, in terms of RFS and adjuvant valproic acid used for 6 months in preventing the development of distal metastases in patients with high risk uveal melanoma. (Cohort 1) II. To assess the efficacy of adjuvant sunitinib, in terms of OS, used for 12 months in patients with high risk uveal melanoma. (Cohort 2) III. To assess the efficacy of adjuvant sunitinib in combination with valproic acid, in terms of OS in patients with high risk uveal melanoma. (Cohort 3) IV. To confirm the safety and tolerability of 6 months of adjuvant sunitinib and adjuvant valproic acid. (Cohort 1) V. To confirm the safety and tolerability of 12 months of adjuvant sunitinib. (Cohort 2) VI. To confirm the safety and tolerability of 12 months of adjuvant sunitinib and valproic acid. (Cohort 3)

TERTIARY OBJECTIVES:

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

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT 1: Participants are randomized to 1 of 2 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.

COHORT 2: Patients receive sunitinib malate PO daily for 12 months in the absence of disease progression or unacceptable toxicity.

COHORT 3: Patients receive sunitinib malate PO daily and valproic acid PO daily for 12 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.

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
Being tested: Sunitinib, Valproic Acid, Sunitinib Malate, Sunitinib Malate + Valproic Acid
Medical subject headings: Uveal Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SunitinibDrug
Also called Sunitinib malate, Sutent, SU11248, 341031-54-7 Butanedioic acid
Given PO
Valproic AcidDrug
Also called VPA, Valproate, Valproate sodium, Depakote
Given PO
Sunitinib MalateDrug
Also called sunitinib, Sutent, SU011248
Given PO
Sunitinib Malate + Valproic AcidDrug
Also called Sunitinib Malate, sunitinib, Sutent, SU011248
Given PO

Study groups in NCT02068586
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Sunitinib Malate + Valproic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: 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)
RFS distribution will be summarized using the method of Kaplan-Meier, and two-sided 90% confidence interval (CI) will be provided.
Measured: 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)
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.
Measured: 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
Proportion of patients completing six months of treatment will be summarized using descriptive statistics.
Measured: 6 months
Incidence of toxicity assessed according to the National Institute of Health Common Terminology Criteria for Adverse Events (NIH CTCAE) version 4.0
Type and grade of toxicity will be assessed on every schedule visit and recorded based on NIH CTCAE 4.0 grading system. Descriptive statistics will be used to summarized type and grade of toxicity.
Measured: Up to 5 years
Quality of life (QOL) assessed by Functional Assessment of Cancer Therapy-General (FACT-G) questionnaires
The FACT-G questionnaires will be scored at baseline, 1 month, 3 months, and 6 months. The difference between two treatment groups will be analyzed with standard t-test at individual evaluation points. Average QOL scores during the study will be calculated and compared between the treatment groups. To estimate the magnitude of the difference between treatment groups, the standardized effect size and minimally important difference will be used. Repeated-measures mixed-effects models with random intercepts and slopes will be used to assess treatment differences in QOL measures over time.
Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Nov 201431 Dec 2027

First posted21 Feb 2014 (estimated)
Study start19 Nov 2014
Primary completion31 Dec 2027 (estimated)
Study completion31 Dec 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Ciliary Body and Choroid Melanoma, Medium/Large SizeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 210 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02068586
Sponsor's protocol ID: 13P.377
Other IDs: 2013-047, JT 2437
Status last verified: Oct 2026
First submitted: 19 Feb 2014
Last updated: 22 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No