A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )

Inclusion Criteria

• Patient with histologically proven stage IIIc or stage IV melanoma who fails to qualify for curative surgery and who bears one or more tumors that are accessible for direct injection
• Patient must have had no more than one previous systemic regimen for management of melanoma; however, adjuvant chemotherapy administered 6 months or longer before entering the trial does not count as a line of treatment
• Absence of circulating serum neutralizing antibodies to CVA21 (titer 1.5 x 10^9/L, platelets > 100 x 10^9/L
• Bilirubin 1.5 x ULN, it must be confirmed that creatinine clearance > 30 mL/minute
• Serum lactate dehydrogenase (LDH) levels 10 cm
• Serum anti-CVA21 neutralizing titer of > 1:16 at baseline
• Presence of any central nervous system (CNS) tumor that has not been stable for at least 3 months off corticosteroids and confirmed by imaging
• Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigators, could cause occlusion into a major vessel in the case of necrosis
• Only measurable tumor had prior local radiotherapy without subsequent nodule progression
• Patient has received chemotherapy within the last 4 weeks prior to first injection
• ECOG score greater than 1
• Estimated life expectancy of less than 6 months
• Pregnancy or breastfeeding
• Primary or secondary immunodeficiency, including immunosuppressive disease, and immunosuppressive doses of corticosteroids (e.g., prednisolone > 7.5 mg per day) or other immunosuppressive medications including cyclosporine, azathioprine, interferons within the past 4 weeks prior to screening
• Positive serology for human immunodeficiency virus (HIV), hepatitis B or C
• Full dose anticoagulation or a history of bleeding diathesis or poorly controlled bleeding in the last month prior to screening
• Previous splenectomy
• Presence of uncontrolled infection
• Presence of unstable neurological disease
• Any uncontrolled medical condition that, in the opinion of the investigator, is likely to place the patient at unacceptable risk during the study or reduce his/her ability to complete the study
• Participation in another study requiring administration of an investigational drug or biological agent within the last 4 weeks prior to screening
• Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
• Participation in any previous melanoma immunotherapy trial within 1 month prior to entry to this trial or any trial of any other investigational agent within the last month prior to entry to this trial
• Active infections or serious general medical conditions
• Patients with previous malignancies should only be permitted if they have been in a continued state of "no evidence of disease" for at least 5 years with the exception of adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of the breast, and basal cell/squamous cell skin cancer
• Known allergy to treatment medication or its excipients and/or to the contrast medium