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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02068586
Recruitment Status : Recruiting
First Posted : February 21, 2014
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Tracking Information
First Submitted Date  ICMJE February 19, 2014
First Posted Date  ICMJE February 21, 2014
Last Update Posted Date May 28, 2020
Actual Study Start Date  ICMJE November 19, 2014
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
Overall survival [ Time Frame: Time of definitive treatment of the primary tumor until death from any cause, assessed at 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma
Official Title  ICMJE A Randomized Phase ll Study of Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Sunitinib
    Given PO
    Other Names:
    • Sunitinib malate
    • Sutent
    • SU11248
  • Drug: Valproic Acid
    Given PO
    Other Names:
    • VPA
    • Valproate
    • Valproate sodium
    • Depakote
    • Epilim
    • Valparin
    • Valpro
    • Stavzor
Study Arms  ICMJE
  • Experimental: Sunitinib
    Patients receive sunitinib malate PO daily for 6 months in the absence of disease progression or unacceptable toxicity
    Intervention: Drug: Sunitinib
  • Experimental: Valproic acid
    Patients receive valproic acid PO daily for 6 months in the absence of disease progression or unacceptable toxicity
    Intervention: Drug: Valproic Acid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 17, 2018)
150
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2014)
90
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takami Sato, MD 215-955-8874
Contact: Melanoma Research Group 215-955-9980
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02068586
Other Study ID Numbers  ICMJE 13P.377
2013-047 ( Other Identifier: CCRRC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Study Sponsor  ICMJE Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Takami Sato, MD Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP