Sunitinib + Valproic Acid for Uveal Melanoma

Overseen By Melanoma 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 Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6-12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two treatments, sunitinib malate (a cancer drug) and valproic acid, in preventing the spread of uveal melanoma (a type of eye cancer). Researchers seek to determine if sunitinib can block signals that promote cancer cell growth and if valproic acid can alter certain genes to slow tumor growth. Candidates may qualify if they have been diagnosed with uveal melanoma, have already treated the primary tumor with surgery or radiation, and are at high risk for cancer spreading. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that sunitinib is safe for people with metastatic uveal melanoma. Patients tolerated sunitinib well, and it showed potential benefits. Research suggests that valproic acid might help reduce the risk and growth of melanoma. Additionally, both sunitinib and valproic acid have proven safe and tolerable for patients with high-risk uveal melanoma. These findings indicate that both treatments are generally well-tolerated, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they're exploring novel combinations for uveal melanoma, a condition with limited options like surgery, radiation, or chemotherapy. Sunitinib malate is unique as it primarily targets specific proteins that promote tumor growth, potentially halting the cancer more effectively than standard therapies. Valproic acid, traditionally used for seizures, may enhance the effectiveness of sunitinib by influencing cancer cell survival pathways. When combined, these drugs could offer a more comprehensive attack on the cancer cells, potentially improving outcomes for patients with this rare eye cancer.

What evidence suggests that this trial's treatments could be effective for uveal melanoma?

Research has shown that sunitinib malate, a treatment in this trial, can help treat uveal melanoma by blocking signals that allow cancer cells to grow. It has improved relapse-free survival, meaning patients remain cancer-free longer. Some studies have linked valproic acid, another treatment option in this trial, to a 36% reduction in melanoma risk. It may alter gene activity, slowing tumor growth. Early research combining these two treatments, tested in one of the trial arms, suggests they may help prevent the spread of high-risk uveal melanoma. ^{1 3 5 6 7}

Who Is on the Research Team?

Takami Sato, MD, PhD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Valproic acid- (Cohort 1, Arm II) Experimental Treatment 1 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 Treatment 1 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 Treatment 1 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 Control 1 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

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

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

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]

In a phase III trial involving 129 patients with metastatic uveal melanoma, the combination of selumetinib and dacarbazine did not significantly improve progression-free survival (PFS) compared to placebo plus dacarbazine, with median PFS of 2.8 months versus 1.8 months.

While the treatment had a tolerable safety profile, common side effects included nausea, rash, and diarrhea, indicating that while selumetinib is safe, it may not provide a substantial benefit over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT). Carvajal, RD., Piperno-Neumann, S., Kapiteijn, E., et al.[2022]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23114504/

A pilot study of sunitinib malate in patients with metastatic ... Sunitinib was safely administered and showed potential clinical benefit in patients with metastatic uveal melanoma. The lack of a correlation between c-kit ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02068586

Study Details | NCT02068586 | Sunitinib Malate or Valproic ... 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.

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.8577

Final results of a pilot study using sunitinib malate in ... Conclusions: Sunitinib at 37.5 mg daily is a feasible treatment with an acceptable safety profile and potential efficacy in metastatic uveal ...

4. cancerresearchuk.org cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-possible-new-treatment-for-eye-cancer-uveal-melanoma-suave

A study looking at a possible new treatment for a type of ... This study was looking to see how well the drug sunitinib (Sutent) worked to treat uveal melanoma. The uvea is the middle tissue layer of the eyeball.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2014-00338

Sunitinib Malate or Valproic Acid in Preventing Metastasis ... 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.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9586

Randomized phase II study of adjuvant sunitinib or valproic ... The primary endpoint was to evaluate the improvement of 2-year overall survival (OS) rate from 70% (historical references) to 85% in each arm.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02068586/

Clinical Trial: NCT02068586 To confirm the safety and tolerability of 6 months of adjuvant sunitinib and adjuvant valproic acid in patients with high-risk uveal melanoma.