A Study of Intratumoral CAVATAK™ in Patients With Stage IIIc and Stage IV Malignant Melanoma (VLA-007 CALM )
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: Coxsackievirus A21 (CVA21)
Intervention description: CVA21 is a live oncolytic virus preparation derived from the non-genetically altered prototype Kuykendall strain of Coxsackievirus A21.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; CALM

Summary:

      The purpose of this study is to assess the clinical efficacy of Intratumoral (IT) CVA21 in
      terms of immune-related Progression-Free Survival (irPFS) at 6 months as monitored via
      immune-related Response Criteria [irRECIST 1.1] (revised Response Evaluation Criteria In
      Solid Tumors [RECIST] 1.1).
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. 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

          3. Absence of circulating serum neutralizing antibodies to CVA21 (titer < 1:16)

          4. 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

          5. 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

          6. Serum lactate dehydrogenase (LDH) levels < or = 1.5 x ULN

          7. Male or female age 18 years or older

          8. Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 or 1

          9. Estimated life expectancy of more than 6 months

         10. Recovered from prior therapy with at least 4 weeks since the last exposure to
             chemotherapy or radiotherapy

         11. Patient is able and willing to provide written informed consent to participate in the
             study

         12. 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:

          1. Mucosal or ocular primary tumors

          2. Bone metastases

          3. Greater than 3 visceral metastases

          4. Any visceral metastases > 10 cm

          5. Serum anti-CVA21 neutralizing titer of > 1:16 at baseline

          6. Presence of any central nervous system (CNS) tumor that has not been stable for at
             least 3 months off corticosteroids and confirmed by imaging

          7. 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

          8. Only measurable tumor had prior local radiotherapy without subsequent nodule
             progression

          9. Patient has received chemotherapy within the last 4 weeks prior to first injection

         10. ECOG score greater than 1

         11. Estimated life expectancy of less than 6 months

         12. Pregnancy or breastfeeding

         13. 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

         14. Positive serology for human immunodeficiency virus (HIV), hepatitis B or C

         15. Full dose anticoagulation or a history of bleeding diathesis or poorly controlled
             bleeding in the last month prior to screening

         16. Previous splenectomy

         17. Presence of uncontrolled infection

         18. Presence of unstable neurological disease

         19. 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

         20. Participation in another study requiring administration of an investigational drug or
             biological agent within the last 4 weeks prior to screening

         21. Any other medical or psychological condition that would preclude participation in the
             study or compromise ability to give informed consent

         22. 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

         23. Active infections or serious general medical conditions

         24. 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

         25. Known allergy to treatment medication or its excipients and/or to the contrast medium