The Malignant Melanoma Clinical Research Program at the OSUCCC – James offers patients access to clinical trials evaluating the newest agents and strategies for preventing, detecting, diagnosing and treating melanoma and other skin cancers.
In addition, preclinical, translational studies are under way investigating the fundamental causes of melanoma, which will lead to still newer agents to help prevent the disease and to treat it more effectively after onset.
The Malignant Melanoma Clinical Research Program also benefits from National Cancer Institute (NCI) funding to the OSUCCC – James that supports the cost of conducting phase I and phase II clinical trials and facilitates the movement of promising phase II studies into phase III national trials.
- Developing and evaluating immunotherapy approaches for malignant melanoma
- Developing a vaccine to slow or stop the growth of malignant melanoma
- Evaluating the use of new agents to inhibit growth of malignant melanoma
OSU-13197: A Phase 1 Study of Trametinib in Combination with Radiation Therapy for Brain Metastases from KRAS-, BRAF-, NRAS- or HRAS- Mutant Malignancies
PI: Evan Wuthrick
NCT ID: NCT02015117
This phase I trial studies the side effects and best dose of trametinib with or without whole-brain radiation therapy in patients with brain metastases. This trial evaluates whether trametinib given with whole brain radiation therapy will make tumor cells more sensitive to radiation therapy. If so, trametinib may be an effective treatment for brain metastases.
- Frequency of dose-limiting toxicities
- Quantification of trametinib in resected brain metastatic lesions utilizing high performance LC/MS/MS
- Overall tolerability and toxicity of the regimen
OSU-13210: Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
PI: Kari Kendra, MD
NCT ID: NCT01763164
A two-arm, randomized, prospective, open-label, multi-center, phase III study comparing the efficacy and safety of MEK162 versus dacarbazine in patients with advanced (Stage IIIC) unresectable or metastatic (Stage IV) NRAS Q61 mutation-positive cutaneous or unknown primary melanoma.
- Progression-free survival
- Overall survival
- Overall response rate
OSU-12118: Phase I Study of Ipilimumab Combined With Whole-Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastasis
PI: Evan Wuthrick
NCT ID: NCT01703507
Evaluates the side effects and best dose of ipilimumab when given together with whole-brain radiation therapy or stereotactic radiosurgery in treating patients with melanoma with brain metastases.
- Maximum tolerated dose of ipilimumab
- Rate of developing new brain metastases in each arm
- Response of extracranial disease/Overall survival/PFS
OSU-13124: A Phase I expansion cohort evaluating the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in patients with unresectable melanoma
PI: Kari Kendra, MD
NCT ID: NCT02120222
This trial studies the side effects of selinexor in treating patients with inoperable melanoma. Targeted therapies such as selinexor might stop the growth of tumor cells by stopping them from dividing.
- Incidence, types and severity of adverse events
- Complete biological response and progression-free survival
- Change in tumor markers by immunohistochemistry
Alliance-A091201: Randomized Phase II Study Comparing the MET Inhibitor Cabozantinib to Temozolomide/Dacarbazine in Ocular Melanoma
PI: Thomas Olencki, MD
NCT ID: NCT01835145
Studies how well cabozantinib-s-malate works compared with temozolomide or dacarbazine in treating patients with melanoma of the eye.
- Progression-free survival at four months
- Overall survival
- Response rate
Allelic Imbalance Mapping to Uncover CSCC Susceptibility Alleles (5R03CA173788)
PI: Amanda Toland, PhD
This work has the potential to validate a new method of identifying cancer susceptibility alleles, to characterize novel putative tumor suppressor genes at 11q24, important in cutaneous squamous cell carcinoma (SCC) tumorigenesis and to identify genetic differences at this region that play a role in SCC risk. The findings may lead to better SCC therapeutic targets and risk prevention strategies.
- Understand the mechanisms by which variants at 11q24 contribute to SCC tumorigenesis and risk and evaluate their candidacy for therapeutic or preventive strategies for cutaneous SCC
- Validate allele-specific imbalance as a method to identify genes and susceptibility alleles important in cancer, and their potential to identify new genes important in SCC
Mast Cells and Immunosuppression in Skin Cancer (5R21ES020462)
PI: Traci Wilgus, PhD
Over a million new cases of non-melanoma skin cancer (NMSC) are reported every year in the U.S. People who have received organ transplants are at especially high risk for NMSCs that are aggressive and more likely to spread to distant sites. These studies examine the involvement of mast cells, a cell of the immune system, in skin cancer development. The findings could lead to better ways of preventing and treating skin cancer.
- Examine the importance of mast cells to cyclosporine A-mediated tumor progression (cyclosporine A is an immunosuppressive drug commonly taken by transplant patients)
- Determine direct effects of cyclosporine A on dermal mast cells
- The findings will generate new information about the contribution of mast cells to the development and growth of UV-induced skin tumors, both in a normal setting and in the presence of immunosuppressive drugs
Melanoma Clinical Research Accomplishments
A phase I dose escalation trial showed that high-dose interleukin-2 followed by sorafenib was safe and feasible in patients with metastatic melanoma or renal cell carcinoma. The study assayed biomarkers related to the antitumor effects of IL-2 that might be altered by sorafenib: percentages of natural T-regulatory cells, myeloid-derived suppressor cells, and STAT5 phosphorylation in T cells. Twelve of 18 patients were evaluated for dose-limiting toxicity. None were observed. Three patients showed partial tumor responses. Published in the Journal of Immunotherapy.
A phase I trial explored whether administration of a cytokine could enhance the antitumor effects of a proteasome inhibitor. Studies had shown that bortezomib combined with interferon-α (IFN-α) induced synergistic apoptosis in human melanoma cell lines and prolonged survival in a murine model of melanoma. This phase I, dose-escalation study evaluated the tolerability and the maximum tolerated dose of bortezomib in combination with IFN-α-2b in 16 patients (eight women, eight men; median age 59) with metastatic melanoma. One patient had a partial response and seven had stable disease. Progression-free survival was 2.5 months; overall survival was 10.3 months. Bortezomib administration did not augment the ability of IFN-α to induce phosphorylation of STAT1 in circulating immune cells; however, it did reduce plasma levels of proangiogenic cytokines. The combination of bortezomib and IFN-α can be safely administered to melanoma patients. Published in the Journal of Immunotherapy.
A phase I study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma. This dose escalation trial evaluated the safety and feasibility of high-dose interleukin-2 (HD IL-2) followed by sorafenib in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC). It examined biomarkers relevant to the antitumor effects of IL-2 that might be altered by sorafenib, including the percentages of natural T-regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and STAT5 phosphorylation (pSTAT5) in T cells. No dose-limiting toxicity was observed in 12 of 18 evaluable patients. Treatment-related toxicity was predictable and did not seem to be additive with this schedule of administration. Three patients showed partial responses. No significant changes in the percentage of circulating Treg and MDSC were observed, and sorafenib did not adversely affect the ability of IL-2 to induce pSTAT5 in T cells. HD IL-2 followed by sorafenib was safe and feasible in patients with MM and RCC. Published in the Journal of Immunotherapy.
Translational Research Accomplishments
Targeting nuclear export proteins might provide a novel therapy for treating melanoma and other cancers. A preclinical study by OSUCCC – James researchers investigated a panel of selective inhibitors of nuclear export (SINE) that target the nuclear export protein exportin 1 (XPO1), also called chromosome region maintenance 1 (CRM1), as a potential treatment for melanoma. They showed that two oral compounds, KPT-276 and KPT-330, significantly inhibited growth of two human melanoma cell lines and showed significant antitumor activity in an animal model at well-tolerated doses. The findings suggested that XPO1 inhibitors could offer a new therapeutic approach for melanoma and possibly other malignancies. The findings helped lead to the clinical trial OSU-13124: A phase I expansion cohort evaluating the SINE KPT-330 in patients with unresectable melanoma. PI: Gregory Lesinski, PhD
miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions. This study explored whether microRNA (miR) expression in borderline melanocytic proliferations would provide a molecular profile that could, along with known prognostic factors, identify lesions with high malignant potential. Analysis of primary cutaneous melanomas revealed an 8.6-fold overexpression of miR-21 and a 7.5-fold overexpression of miR-155 compared with benign naevi. When borderline lesions were categorized by mitotic activity and Breslow thickness, miR-21 was associated with mitotic activity and miR-155 was associated with thickness. Among 14 patients with borderline lesions who underwent sentinel lymph-node biopsy (SLNB), positive biopsies were associated with increased miR-21 and miR-155 in the primary lesion compared with lesions with a negative SLNB. MicroRNA expression profiles can be used to characterize atypical melanocytic lesions. Published in the British Journal of Cancer.
MIF antagonist (CPSI-1306) protects against UVB-induced squamous cell carcinoma. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in cutaneous squamous cell carcinomas (SCC). This study used the small-molecule MIF inhibitor (CPSI-1306) to determine whether MIF inhibition could reduce UVB light-induced inflammation and squamous carcinogenesis. The study, which used hairless mice, suggested that CPSI-1306 could slow the rate of tumor development and decrease tumor burden. Overall, the findings suggest that MIF inhibition is a promising strategy for prevention of the deleterious cutaneous effects of acute and chronic UVB exposure. Published in Molecular Cancer Research