Clinical Trials

Although important progress has been made in the treatment of melanoma, many important clinical questions still need to be answered. We continue to explore the frontiers of discovery in the treatment of melanoma thanks in part to the many patients who willingly to participate in new treatment trials. Participation in a new treatment trial can be a rewarding option for the appropriate patient.

Melanoma Clinical Trials Available at Johns Hopkins (Kimmel Cancer Center searchable database.)

Eastern Cooperative Oncology Group

Summary of Current Melanoma Trials

Trials for Patients with Stage II or III Melanoma:

J0650: Multicenter Selective Lymphadenectomy Trial II (MSLT-II). MSLT-II is a Phase III randomized trial that will compare, for patients with a positive sentinel lymph node (SLN) biopsy, the outcomes following close observation (ultrasound examination) of the draining lymph node basin versus immediate surgical removal of all the lymph nodes in that region (the current standard of care). SLN mapping is a surgical staging technique combined with pathology confirmation, which is used to determine if melanoma cells have spread from the primary skin site to the regional draining lymph nodes. In general, spreading of melanoma to the draining lymph nodes is associated with an increased risk for developing widespread disease. For 70-80% of patients found to have microscopic tumor deposits in their draining lymph nodes, the SLN biopsy technique removes all of the tumor-involved lymph nodes in the area, but for other patients microscopic tumor persists in the remaining lymph nodes. If it is proven safe to observe patients with a positive sentinel lymph node as opposed to immediate complete lymph node dissection, future patients could be spared the potential side effects and complications of a more radical surgical procedure. Patients must be assigned to one of the two arms of the study within 4 months of their primary melanoma skin biopsy. Study participants must be at least 18 years old and cannot have their primary melanoma site located in the eye (ocular) or the mucous membranes (mucosal). Patients who do not develop recurrent disease may be followed for up to 10 years. Johns Hopkins is one of many institutions involved in this international study, which will eventually enroll thousands of patients.

J1112: A FEASIBILITY AND TOXICITY STUDY OF A GM-CSF SECRETING ALLOGENEIC MELANOMA VACCINE (MELANOMA GVAX) ADMINISTERED ALONE OR IN COMBINATION WITH CYCLOPHOSPHAMIDE IN SUBJECTS WITH SURGICALLY RESECTED AT-RISK MELANOMA
This melanoma vaccine trial is a phase I study for patients with stage IIB, IIC, III or IV melanoma who have undergone complete surgical resection but who are at risk for developing recurrence of their disease.  Melanoma GVAX is an investigational vaccine designed to teach the immune system to recognize and eliminate melanoma tumors, which may persist at a microscopic level after surgery.  In this study, some patients will receive Melanoma GVAX alone (low dose or high dose), while others will receive Melanoma GVAX plus low-dose cyclophosphamide. Cyclophosphamide is a chemotherapy frequently used in cancer treatment.  In this study, it will be given at a low dose to try to augment the effects of the vaccine.  The purpose of this study is to find the optimal dose of Melanoma GVAX, with or without cyclophosphamide, that is safe and that produces an immune response.  The vaccine will be given in the skin monthly for four doses.  Eligible patients must be ≥18 years old with melanoma arising in the skin or mucous membranes (such as the nostrils, mouth, or rectum) that has been completely resected at least 2 weeks but no more than 6 months prior to receiving the first treatment on this trial.  Patients with melanomas arising in the eye (ocular) are not eligible.  Participants must not have hepatitis, HIV, or any history of an immune disorder.  Patients must not have received any type of cancer immunotherapy, such as interleukin-2, interferon alfa or other melanoma vaccines.  Patients will be evaluated on this trial for 6 months and then followed yearly for 5 years.

Treatment Trials for Advanced Melanoma (Stage III or IV)

J10122: An Open Label, Dose Escalation, Phase I Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the BRAF Inhibitor GSK2118436 in Combination with the MEK Inhibitor GSK1120212 in Subjects with BRAF Mutant Metastatic Melanoma
The purposes of this study are: 1) to test the safety of the drugs GSK1120212 and GSK2118436 taken separately and together, and 2) to examine how well these drugs work together in mediating tumor regression in patients with locally advanced or metastatic melanoma.  Individually, both drugs have been shown in previous studies to cause the regression of advanced metastatic melanoma. Scientific evidence suggests that the combination may improve outcomes.  Eligible subjects must have measurable metastatic melanoma tumors that contain the BRAF V600E mutation. Patients will be assigned to one of three treatment groups: BRAF inhibitor only, BRAF inhibitor plus high dose MEK inhibitor, or BRAF plus low dose MEK inhibitor.  Both medications are orally administered and need to be taken every day.  Patients will be seen every two weeks for the first month and then monthly thereafter.

The following conditions may exclude enrollment in this study:
• Prior exposure to BRAF or MEK inhibitors
• On warfarin (Coumadin)
• Certain ophthalmologic (eye) problems
• Uncontrolled hypertension, diabetes, hyperlipidemia, coagulopathy or NYHA Class II, III, or IV heart failure
• HIV, Hepatitis B or Hepatitis C infection
• Untreated or symptomatic melanoma metastases in the central nervous system (brain, spinal cord)
• Pregnancy
• Glucose-6-phosphate-dehydrogenase deficiency (G6PD deficiency)

J08113: Phase Ib Multicenter Multidose Study of an Anti-PD-1 Monoclonal Antibody (MDX-1106) in Patients with Selected Refractory or Relapsed Malignancies. This clinical trial is designed to evaluate the safety and tolerability of the human monoclonal antibody MDX-1106 in treating patients with advanced cancers. MDX-1106 blocks PD-1, a molecule found on the surface of activated T lymphocytes (immune cells). Normally, PD-1 dampens immune responses at the appropriate time, turning off immune activation. However, laboratory evidence suggests that PD-1 may also suppress immune responses against cancer, and that blocking PD-1 may enhance anti-tumor immunity thereby controlling tumor growth. This is the second trial to evaluate MDX-1106 in cancer patients. In the first-in-human clinical trial recently conducted at Johns Hopkins and 3 other centers, patients received progressively higher doses of MDX-1106 as a single intravenous infusion every 1-3 months. Tumor regressions were observed in some patients with melanoma, kidney, colon and lung cancer, and there were minimal side effects. This new trial will use more frequent dosing of MDX-1106, every 2 weeks in 2-month cycles. Patients with advanced metastatic melanoma (stage III or IV) whose disease has recurred after standard treatment may be eligible for enrollment, regardless of the site of their original melanoma (skin, eye, mucosal, unknown). In addition to melanoma, patients with advanced cancers of the kidney, lung and prostate will be included. Because MDX-1106 has immune stimulatory properties, patients with autoimmune diseases are not eligible.

J0918: A Phase 1, Open-label, Multicenter, Dose-escalation, Multidose Study of MDX-1105 Administered Every 14 Days in Subjects with Selected Advanced or Recurrent Solid Tumors. This is a first-in-human phase I trial of a monoclonal antibody targeting Programmed Death Ligand 1 (PD-L1). PD-L1 is a molecule involved in inhibiting the immune system, such that in healthy patients it protects against certain autoimmune diseases. In patients with cancer, however, PD-L1 is often expressed on the tumor cell surface and may diminish the efficacy of an immunologic anti-tumor attack. MDX-1105 blocks PD-L1, thereby allowing the patient’s immune system to more readily recognize and destroy cancer cells. The primary objective of this study is to assess the safety and tolerability of MDX-1105 when administered intravenously every 14 days, and to determine the maximum tolerated dose of this drug. The trial is also designed to evaluate the anti-tumor effects and pharmacologic properties of MDX-1105. Nearly 300 subjects with measurable, advanced, recurrent melanoma or other tumors, including cancers of the lung, ovary, kidney, colon, stomach, pancreas, and breast will be enrolled. Participants with melanoma must have unresectable treatment-refractory Stage III or IV disease. All melanomas regardless of primary site of disease will be allowed. Patients must have a good performance status and adequate hematologic, renal and hepatic function. Prior chemotherapy or IL-2 is allowed, but patients who have undergone therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies, or any other agents that target T cell co-stimulation, will not be eligible.

J0794: A Phase I/II dose escalation trial to evaluate RAF265 (CHIR-265) to treat patients with locally advanced or metastatic melanoma. The purpose of this study is to find the highest safe dose of RAF265 that can be given to patients who have locally advanced or metastatic melanoma, what side effects these patients may experience, and whether RAF265 is effective in treating melanoma. RAF265 is a “kinase inhibitor” which has been shown to slow or inhibit the growth of melanoma cells in the laboratory and in animals. This is the first time that RAF265 is being given to people. RAF265 is given by mouth, either daily or weekly, for 28-day cycles. During the first week of the study, RAF265 is given in the outpatient clinic, and blood samples and tumor biopsies are taken at various time intervals afterwards to determine the activity and clearance of the drug. Patients with metastatic melanoma arising from any site (skin, mucosal, ocular) may be eligible for this study. Patients previously treated with a VEGF inhibitor (for example, Avastin) or a RAF inhibitor (for example, Nexavar), or those with significant heart problems or requiring anticoagulants (blood thinners), will not be eligible for this trial. Patients on treatment will be assessed with radiological scans approximately every 2 months, and can continue treatment provided that they do not have melanoma progression or undue toxicity from RAF265.

J1045: The TEAM Trial (Tasigna Efficacy in Advanced Melanoma): A Randomized, Phase III, Open Label, Multi-center, Two-arm Study to Compare the Efficacy of Tasigna ® Versus Dacarbazine (DTIC) in the Treatment of Patients With Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation.  This is a phase III multicenter study for patients with locally advanced or metastatic mucosal melanoma (arising in the mucous membranes, such as the nostrils, mouth, or rectum), acral melanoma (arising in the palms, soles or under the nails), or solar melanoma (arising in skin with long-term sun damage) that cannot be removed by surgery.  The purpose of this study is to compare the efficacy (progression free survival) of nilotinib (Tasigna) versus dacarbazine (DTIC) in patients with c-Kit mutated melanoma. ‘C-Kit mutated’ means that a cancer has been genetically tested and a mutation in the c-Kit gene is present. Patients will be randomly assigned to receive either nilotinib or dacarbazine therapy.  Dacarbazine is the only FDA-approved chemotherapy drug for metastatic stage IV melanoma.  Nilotinib is an oral medication that blocks some of the molecules needed for tumor growth and is currently used to treat some types of leukemia.  Recent phase II trials suggest that drugs like nilotinib may be effective in patients with melanoma harboring a c-Kit mutation.  To join this study, a patient must have stage III unresectable or stage IV metastatic disease with one or more radiologically measurable lesions of at least 1 cm diameter.  The patient’s tumor must have one of several specific c-Kit mutations.  Patients with c-Kit amplifications only and no mutation are excluded.  Tumors may not have any NRAS or BRAF mutations.  Patients may not have brain involvement and may not have had any prior treatment with tyrosine kinase inhibitors (such as imatinib) or dacarbazine.

ECOG 2607: Phase II Study of Dasatinib in Patients with Unresectable Locally Advanced or Metastatic Mucosal, Acral, or Solar Melanoma.  This is a phase II multicenter study for patients with locally advanced or metastatic mucosal melanoma (arising in the mucous membranes, such as the nostrils, mouth, or rectum), acral melanoma (arising in the palms, soles or under the nails), or solar melanoma (arising in skin with long-term sun damage) that cannot be removed by surgery.  The purpose of this study is to evaluate if dasatinib can cause tumor regression in patients with these specific types of melanoma.  Dasatinib is an oral medication that blocks some of the molecules needed for tumor growth.  Dasatinib has historically been used in patients with certain types of leukemia, but has shown some activity in patients with certain types of melanoma.  On this trial, patients will receive dasatinib by mouth twice a day. Treatment may continue for as long as benefit is shown. After finishing treatment, patients will be evaluated periodically for up to 5 years. Eligible patients must be at least 18 years old, have measurable disease and be at least 4 weeks out from chemotherapy, biological therapy, or radiation therapy. Patients who have had previous imatinib or sunitinib are not eligible. Patients with melanomas arising in the eye (ocular) are not eligible.  Prior radiotherapy to a measurable lesion is allowed provided there is radiographic evidence of progression of that lesion.  Patients may have brain metastases provided they have completed radiotherapy or surgical treatment, there is no evidence of progression for at least 8 weeks, and they do not require steroids.  Tumor biopsy material must be available to evaluate genetic changes associated with susceptibility to dasatinib.