Safety and Immune Response to a Multi-component Immune Based Therapy (MKC1106-MT) for Patients With Melanoma.

Study Overview
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Brief Summary
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A dose comparison of a multi-component active immunotherapy designed to stimulate an immune reaction to specific tumor associated antigens which are highly expressed on melanomas.

Detailed Description
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The multi-component active immunotherapy, MKC1106-MT, consists of 1 plasmid dose and 2 peptides doses designed to stimulate an immune reaction to two tumor associated antigens (Melan-A and tyrosinase). The plasmid component will be administered on Days 1,4, 15 and 18 of each treatment cycle followed by administration of peptides on Days 29 and 32 of the treatment cycle. All components will be administered separately into superficial inguinal lymph nodes under ultrasound guidance.

Official Title
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A Phase 1/2, Open Label, Non-Randomized Dose Escalation Study to Evaluate the Safety, Tolerability, Immune Response and Clinical Response of Multiple Doses of MKC1106-MT in Subjects With Advanced Melanoma

Conditions
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Advanced Melanoma, Stage III and IV Melanoma

Intervention / Treatment
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* Biological: Biological: MKC1106-MT
* Biological: Biological: MKCC1106-MT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of locally advanced or metastatic melanoma (American Joint Committee on Cancer [AJCC 6th edition] stage IIIB, IIIC or IV) that is refractory to standard therapy or for which no curative standard therapy exists. Patients enrolled in the Phase 2 portion of the trial must have measurable disease by the RECIST criteria ECOG performance status of 0 or 1 Life expectancy = 3 months 18 years of age or older at screening evaluation Positive for HLA-A2, and more precisely, express A*0201 as assessed by DNA typing Tumor material from prior biopsy / surgical resection available for analysis of expression of melanoma specific antigens Adequate bone marrow reserve as evidenced by: Absolute neutrophil count (ANC) = 1,000/?L & Platelet count = 75,000/?L Adequate renal function as evidenced by: serum creatinine = 1.5 mg/dL Adequate hepatic function as evidenced by: Serum total bilirubin = 2.0 mg/dL & SGOT/SGPT = 3 times the ULN for the reference lab (= 5 the ULN for the reference lab for subjects with known hepatic metastases) Subjects must have recovered to at least baseline or Grade 1 toxicity from the effects of any prior surgery, radiotherapy or other therapies including but not limited to chemotherapy Women of childbearing potential as well as fertile men and their partners must agree to use an effective method of contraception or to abstain from sexual intercourse during the clinical trial and for 90 days following the last dose of the investigational new drug Subjects must be able to provide informed consent for participation in the clinical trial before any protocol-specific clinical trial procedure is performed Exclusion Criteria: No systemic infection requiring treatment Symptomatic brain metastases and/or progression of CNS metastases within the past 4 weeks; patients with treated CNS metastases (by surgery and/or radiation), who are neurologically stable, and who are no longer taking glucocorticoids, are eligible Subjects with autoimmune disorders, including, but not limited to: systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, mixed connective tissue disease, ankylosing spondylitis, Hashimoto's thyroiditis, bullous pemphigus, sarcoidosis, Behçet's syndrome, vasculitis, familial Mediterranean fever, Wegener's granulomatosis or Goodpasture's syndrome Positive HIV, hepatitis B or hepatitis C antibody test Subjects who underwent allogeneic transplant New York Heart Association Grade III or IV congestive heart failure Medical, sociological or psychological conditions that may compromise compliance or participation in the clinical trial or interfere with the interpretation of the results Subjects who have taken drugs that negatively affect immune function such as systemic corticosteroids or other immunomodulatory drugs including, but not limited to, interferon-alpha, interferon-beta, interleukin-2, etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept or efalizumab, within one month preceding the screening Subjects who are lactating, pregnant, or planning to become pregnant within three months of treatment completion Subjects who have received any investigational drug within the preceding four weeks of enrollment Subjects who have affected inguinal lymph nodes (metastatic process) or lack of inguinal lymph nodes (resection)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose Peptide Cohort<br> | Biological: Biological: MKCC1106-MT<br>* Cancer Vaccine, Immunotherapy<br>|
| Experimental: High-Dose Peptide Cohort<br> | Biological: Biological: MKC1106-MT<br>* Cancer Vaccine, Immunotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Is to assess the safety and tolerability of MKC1106-MT regimen |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the immune response (by tetramer and ELISPOT analysis) of MKC1106-MT when administered to subjects with advanced melanoma |  | 6 Weeks | 
| To determine pMEL-TYR plasmid level in the blood by PCR analysis |  | 6 Weeks | 
| To determine target antigen expression (Melan A and tyrosinase) and beta2 microglobulin expression in the tumor tissue |  | 6 Weeks | 
| To document any preliminary evidence of clinical response |  | 6 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Melanoma, Cancer Vaccine