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

About this trial
This is an interventional treatment trial for Malignant Melanoma focused on measuring Melanoma, CALM
Eligibility Criteria
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 < 1:16)
- At least one tumor 0.5 to 10 cm in the longest diameter must be suitable for injection and at least one tumor must be equal to or greater than 1 cm and qualified to be a target lesion for RECIST 1.1 criteria
Patient must have adequate hematologic, hepatic and renal function, defined as:
- Absolute neutrophil count (ANC) > 1.5 x 10^9/L, platelets > 100 x 10^9/L
- Bilirubin < 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) < 2.5 x ULN
- Serum creatinine < 1.5 x ULN; if > 1.5 x ULN, it must be confirmed that creatinine clearance > 30 mL/minute
- Serum lactate dehydrogenase (LDH) levels < or = 1.5 x ULN
- Male or female age 18 years or older
- Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 or 1
- Estimated life expectancy of more than 6 months
- Recovered from prior therapy with at least 4 weeks since the last exposure to chemotherapy or radiotherapy
- Patient is able and willing to provide written informed consent to participate in the study
- Fertile males and females must agree to the use of an adequate form of contraception, e.g., condoms for males. A negative pregnancy test is required in female patients of childbearing potential.
Exclusion Criteria:
- Mucosal or ocular primary tumors
- Bone metastases
- Greater than 3 visceral metastases
- Any visceral metastases > 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
Sites / Locations
- Moores UCSD Cancer Center
- St Mary's Medical Center
- Mount Sinai Medical Center
- Rush University Medical Center
- Oncology Specialists, SC
- Investigative Clinical Research of Indiana
- Atlantic Melanoma Center
- Providence Cancer Center
- Mary Crowley Cancer Research Centers
- Huntsman Cancer Institute
Arms of the Study
Arm 1
Experimental
Intratumoral injection
Each patient will receive 4 separate Coxsackievirus A21 (CVA21) administrations in the first 8 days on trial (Days 1, 3, 5 and 8), followed by a fifth dose 2 weeks later (Day 22) and further administrations at 3 weekly intervals (Days 43, 64, 85, 106 and 127, up to a maximum of 10 sets of injections) until confirmed disease progression or development of excessive toxicity. Subjects with stable disease or better at Day 127 were eligible to receive up 9 more sets of CVA21 administrations under an extension protocol (VLA-008).