CY503 for the Treatment of Malignant Melanoma Stage IV After Failure of Prior Therapy

A Phase II Multicenter Study to Test Progression-free and Overall Survival of CY-503 in the Treatment of Patients With Unresectable Stage IV Metastatic Melanoma After Antineoplastic Treatment Failure

The trial is designed as a phase II evaluation of the effect of CY-503 on progression free survival (PFS) in patients with stage IV malignant melanoma after failure of prior therapy. The aim of the study is at least a rate of 25% (PFS >/= 3 months).

Inclusion Criteria:

• Histologically confirmed, unresectable, Stage IV metastatic melanoma
• Failure of prior chemotherapy and / or immunotherapy based regimen
• Measurable disease (based on RECIST criteria)
• Males and females of at least 18 years of age
• Women of reproductive potential (defined as being <1 year post-menopausal) must have a negative pregnancy test within 3 days prior to randomization; and men and women of reproductive potential must agree to practice an effective method of avoiding pregnancy
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
• Life expectancy of at least 3 months
• WBC ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelet count ≥100,000/mm3
• Bilirubin ≤ 1.5 mg/dL (25.65 μmol/L) (unless due to Gilbert's syndrome in which case the bilirubin should be ≤3.5 mg/dL (59.86 μmol/L)), aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN); hepatic alkaline phosphatase ≤ 3.0 × ULN
• LDH ≤ 2.5 upper limit of normal (ULN)
• Serum creatinine ≤ 1.5 mg/dL (132.60 μmol/L), proteinuria < 2.0 g/24 hr urine
• Patients who have had prior treatment with adjuvant or palliative immunotherapy are eligible provided that therapy ended at least 1 month prior to randomization and all treatment-related toxicities have resolved
• Patients with bone metastasis should be evaluated by the investigator and prior treatment should be finished at least 1 month prior to randomization
• Prior radiotherapy (for palliative care only) is allowed provided there is measurable/evaluable disease outside of the radiation field and all radiation-related toxicities have resolved; if there is only one measurable lesion it may not have been irradiated unless subsequent progression has been documented
• Patients who had prior major surgery are eligible if at least 4 weeks have passed since their surgery and all surgical wounds have healed prior to randomization and at least one measurable tumor is present
• All toxicities related to prior adjuvant therapy must have resolved
• Written informed consent

Exclusion Criteria:

• Pregnancy or nursing
• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer
• Current or planned participation in a research protocol
• Received an investigational agent within 4 weeks prior to randomization
• Brain metastases or primary brain tumors, symptomatic pleural effusion or ascites requiring paracentesis
• Ocular melanoma
• History of prior malignancies within the past 5 years other than non-melanomatous skin cancers that have been controlled, carcinoma in situ of the cervix, T1a or b prostate cancer noted incidentally during a transurethral resection of prostate (TURP) with prostate-specific antigen (PSA) values within normal limits since TURP, or superficial bladder cancer
• Any evidence of or history elicited by the investigator of symptomatic cerebrovascular events within 6 months prior to randomization; or any history or evidence of pulmonary embolism or thrombophlebitis requiring anticoagulant therapy
• Any current evidence of hematemesis, melena, hematochezia, or gross hematuria
• Elective surgery planned during the study period through 30 days after the last dose of CY-503
• History of hypersensitivity to previously administered mistletoe
• Prior therapy with mistletoe
• History of primary immunodeficiency
• Known human immunodeficiency virus (HIV) or known active viral hepatic infections
• Prior treatment with CY-503
• A general medical or psychological condition or behaviour in the opinion of the investigator, might not permit the patient to complete the study or sign the informed consent.