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Compensation: Varies

Number of Visits: 3

Duration: 6-12 months

210 Participants Needed

Sunitinib + Valproic Acid for Uveal Melanoma

Overseen ByMelanoma Research Group

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Must not be taking: Anticonvulsants, CYP3A4 inhibitors

Disqualifiers: Other malignancy, Metastatic melanoma, Cardiovascular disease, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using any strong CYP3A4 inhibitors or inducers and switch to a different medication with a weaker interaction before joining. If you are on valproic acid for non-cancer reasons, you may need to switch to another medication. Chronic use of aspirin over 81 mg/day is also not allowed.

What data supports the effectiveness of the drug combination Sunitinib and Valproic Acid for treating uveal melanoma?

Research shows that Sunitinib, a drug that targets specific proteins in cancer cells, has shown potential benefits in patients with metastatic uveal melanoma, with some patients experiencing stable disease for over a year. Additionally, Valproic Acid, known for its antiangiogenic properties, may help reduce cancer cell movement, which is crucial in preventing cancer spread.¹ ² ³ ⁴ ⁵

Is the combination of Sunitinib and Valproic Acid safe for humans?

Sunitinib has been safely administered in patients with metastatic uveal melanoma, but common side effects include fatigue, diarrhea, bleeding, loss of appetite, hand-foot syndrome (redness and swelling of the hands and feet), low thyroid function, and skin rash. Valproic Acid is not specifically mentioned in the context of uveal melanoma, but it is generally used as a medication for other conditions and may have its own side effects.¹ ² ⁴ ⁵ ⁶

How is the drug Sunitinib + Valproic Acid unique for treating uveal melanoma?

The combination of Sunitinib and Valproic Acid is unique for treating uveal melanoma because it targets multiple pathways involved in cancer progression, including inhibiting angiogenesis (formation of new blood vessels) and affecting cell motility, which are crucial for metastasis. This approach is different from other treatments that may focus on a single pathway or mechanism.¹ ² ⁴ ⁵ ⁶

What is the purpose of this trial?

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.

Research Team

Takami Sato, MD, PhD

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

Adults over 18 with high-risk uveal melanoma treated within the last 6 months, not pregnant or breastfeeding, and willing to use contraception. They must have a good performance status, no other cancers in the past 5 years (with some exceptions), no history of severe allergies to trial drugs, and their organs must function well.

Inclusion Criteria

If female, no pregnancy

Less than 6 months from the date that local treatment (surgical or radiation) of the primary tumor was finalized

You have been diagnosed with uveal melanoma.

See 12 more

Exclusion Criteria

You had any other type of cancer, except for certain types of skin, cervical, or early stage prostate cancer, within the past 5 years.

You have uveal melanoma that has spread to other parts of the body.

You had a serious allergic reaction to sunitinib or valproic acid before, or you can't take sunitinib or valproic acid.

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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sunitinib malate or valproic acid daily for 6 to 12 months depending on cohort assignment

6-12 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, every 6 months for 3 years, then annually

Treatment Details

Interventions

Sunitinib Malate
Valproic Acid

Trial Overview The trial is testing if sunitinib malate or valproic acid can prevent high-risk eye melanoma from spreading. Participants are randomly chosen to receive either drug. Sunitinib may block tumor growth signals; valproic acid might suppress tumor growth by changing gene expression.

Participant Groups

4Treatment groups

Experimental Treatment

Active Control

Group I: Valproic acid- (Cohort 1, Arm II)Experimental Treatment1 Intervention

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

Group II: Sunitinib- (Cohort 1, Arm I)Experimental Treatment1 Intervention

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

Group III: Sunitinib Malate (Cohort 2)Experimental Treatment1 Intervention

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

Group IV: Sunitinib Malate + Valproic Acid (Cohort 3)Active Control1 Intervention

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

Sunitinib Malate is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Sutent for:

Renal cell carcinoma
Gastrointestinal stromal tumor
Pancreatic neuroendocrine tumors

Approved in United States as Sutent for:

Renal cell carcinoma
Gastrointestinal stromal tumor
Pancreatic neuroendocrine tumors

Approved in United Kingdom as Sutent for:

Advanced and/or metastatic renal cell carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sidney Kimmel Cancer Center at Thomas Jefferson University

Lead Sponsor

Trials

164

Recruited

10,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Findings from Research

Uveal melanoma, the most common eye cancer in adults, has a significant risk of metastasis, with up to 50% of patients developing metastases within 15 years after treatment of the primary tumor.

Current systemic therapies for uveal melanoma have limited efficacy, but ongoing research is exploring new candidate drugs, including bortezomib and MEK inhibitors, to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic agents in uveal melanoma.Velho, TR., Kapiteijn, E., Jager, MJ.[2012]

The SUMIT trial is a phase III study involving 128 patients with metastatic uveal melanoma, testing the combination of selumetinib (a MEK1/2 inhibitor) and dacarbazine, aiming to improve progression-free survival compared to dacarbazine alone.

Previous studies indicated that selumetinib showed antitumor effects in pre-clinical models and improved outcomes in a phase II trial, making this combination a promising approach for patients who have not received prior systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT).Carvajal, RD., Schwartz, GK., Mann, H., et al.[2018]

The study evaluated the effectiveness of the MEK inhibitor selumetinib in combination with various drugs for treating metastatic uveal melanoma, finding that combining selumetinib with the chemotherapy drug DTIC did not enhance its antitumor effects, aligning with previous clinical trial results.

However, combinations of selumetinib with ERK and mTORC1/2 inhibitors showed promising efficacy in patient-derived xenograft models, suggesting these combinations may be more effective treatment strategies for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selumetinib-based therapy in uveal melanoma patient-derived xenografts.Decaudin, D., El Botty, R., Diallo, B., et al.[2019]