A Study of Talimogene Laherparepvec in Stage IIIc and Stage IV Malignant Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Talimogene Laherparepvec
Intervention description: Up to 4 mL of 10⁸ pfu/mL/per intratumoral injection
Intervention MeSH terms: Talimogene laherparepvec
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: gene transfer; gene therapy; oncolytic virus; GM-CSF; melanoma

Summary:

      The primary objective of the study was to assess the clinical efficacy of talimogene
      laherparepvec in terms of tumor response rates.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologically proven stage IIIc (including two or more palpable lymph
             nodes, extracapsular or in-transit metastases) or stage IV melanoma that is not
             eligible for curative surgery and who have one or more tumors that are accessible for
             direct injection.

          2. Tumors 0.5 to 10 cm in the longest diameter that are suitable for injection (i.e. not
             bleeding or weeping).

          3. Serum lactate dehydrogenase (LDH) levels ≤ 2.0 times the upper limit of normal.

          4. Aged 18 years or more.

          5. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.

          6. Clinically immunocompetent.

          7. Recovered from prior therapy with at least 4 weeks since the last exposure to
             chemotherapy or radiotherapy.

          8. Total white cell count ≥ 3.0 x 10^9/L, platelet count ≥ 80 x 10^9/L.

          9. Serum creatinine ≤ 0.2 mmol/L.

         10. Bilirubin ≤ 1.5 times the upper limit of the normal range, aspartate aminotransferase
             (AST)/alanine aminotransferase (ALT) equal to or less than twice the upper limit of
             the normal range and alkaline phosphatase equal to or less than twice the upper limit
             of the normal range.

        Exclusion Criteria:

          1. Participation in any previous melanoma immunotherapy trial within one 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.

          2. 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
             or compression in the case of tumor swelling or erosion into a major vessel in the
             case of necrosis.

          3. Pregnancy, lactation or lack of effective contraception in women of child-bearing
             potential; lack of effective contraception in men if the partner is of child-bearing
             potential; women must have been practising an effective contraceptive method for at
             least three months prior to entry in to the trial (hormonal contraception or
             intrauterine device in conjunction with a barrier method OR surgically sterilised).
             Men must use a condom or be surgically sterilised.

          4. Major surgery within the 14 days prior to entry to the trial.

          5. Intercurrent serious infections within the 28 days prior to entry to the trial.

          6. Life-threatening illness unrelated to cancer.

          7. Treatment with antiviral agents within the 14 days prior to entry to the trial.

          8. Uncontrolled congestive cardiac failure.

          9. Clinically active autoimmune disease.

         10. Dermatoses involving or near to the tumors to be injected. Limb tumors may not be
             injected if active dermatoses are present on the same limb. Trunk and head and neck
             tumors must not be injected if dermatoses are present within 50 cm of the tumor.

         11. Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C or
             syphilis.

         12. Patient only has injectable tumors that are not potentially resectable in the case of
             tumor necrosis or swelling.

         13. Previous history of malignancies of other types that have occurred or recurred within
             the previous 5 years with the exception of cone biopsied carcinoma of the cervix.

         14. Corticosteroid use.