Evaluation of a New Vaccine Treatment for Patients With Metastatic Skin Cancer
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Immunotherapeutic GSK2302025A, different formulations
Intervention description: Intramuscular administration
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PRAME; Cancer immunotherapeutic; Malignant melanoma; ASCI (Antigen-Specific Cancer Immunotherapeutic)

Summary:

      The purpose of this clinical study is to examine the safety, immunogenicity and clinical
      activity of the immunotherapeutic product GSK2302025A (also referred to as recPRAME + AS15
      Antigen-Specific Cancer Immunotherapeutic [ASCI]) administered as a first line treatment in
      patients with unresectable and progressive metastatic cutaneous melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patient with histologically proven cutaneous melanoma. Phase I segment:
             All melanoma patients with stage IV M1b and stage IV M1c including completely resected
             stage IV patients but with the exception of stage IV M1c disease with serum lactate
             dehydrogenase > 1.5 x Upper Limit of Normal or with involvement of the Central Nervous
             System.

             Phase II segment: All melanoma patients with measurable, unresectable stage III
             melanoma including in-transit metastasis (with (N3) or without (N2c) nodal metastasis)
             and stage IV M1a melanoma. The patient should have documented progressive disease
             within 12 weeks of registration into the trial. Patients with resected stage IV and
             with stage IV M1b or M1c disease cannot be included.

          2. Written informed consent for PRAME expression screening and gene profiling on resected
             tumor tissue and for the complete study has been obtained from the patient prior to
             shipment of the sample for expression testing and prior to the performance of any
             other protocol-specific procedure.

          3. The patient is >= 18 years old at the time of signing the first informed consent form.

          4. The patient's tumor shows expression of the PRAME antigen as determined by RT-PCR
             analysis or any updated technique on fresh tissue sample.

          5. Eastern Cooperative Oncology Group performance status of 0 or 1.

          6. The patient has adequate bone marrow reserve, renal, adrenal and hepatic function as
             assessed by standard laboratory criteria.

          7. Female patients of non-childbearing potential may be enrolled in the study.
             Non-childbearing potential is defined as current tubal ligation, hysterectomy,
             ovariectomy or post-menopause.

          8. Female patients of childbearing potential may be enrolled in the study, if the
             patient:

               -  has practiced adequate contraception for 30 days prior to the study product
                  administration, and

               -  has a negative pregnancy test on the day of administration, and

               -  has agreed to continue adequate contraception during the entire treatment period
                  and for 2 months after the completion of the study product administration series.

          9. In the view of the investigator, the patient can and will comply with all the
             requirements of the protocol.

        Exclusion Criteria:

          1. The patient has at any time received systemic chemotherapy, (bio)-chemotherapy or
             CTLA-4 monoclonal antibodies for metastatic disease.

          2. The patient is scheduled to receive any other anticancer treatment, including but not
             limited to (bio)-chemotherapeutic or immunomodulating agents and radiotherapy.

          3. The patient has received any cancer immunotherapy containing the PRAME antigen or any
             cancer immunotherapy for his/her metastatic disease.

          4. The patient requires concomitant treatment (more than 7 consecutive days) with
             systemic corticosteroids or any other immunosuppressive agents.

          5. Use of any investigational or non-registered product (drug or vaccine) other than the
             study product within the 30 days preceding the first ASCI dose injection or planned
             use during the study period

          6. The patient has (had) previous or concomitant malignancies at other sites (including
             carcinoma in situ), except effectively treated non-melanoma skin cancers or carcinoma
             in situ of the cervix or effectively treated malignancy that has been in remission for
             over 5 years and is highly likely to have been cured.

          7. The patient has an allergy to any component of the study investigational product or
             has a history of previous allergic reactions to vaccinations.

          8. The patient has a history of confirmed adrenal dysfunction.

          9. The patient has an autoimmune disease such as, but not limited to, multiple sclerosis,
             lupus, and inflammatory bowel disease.

         10. The patient is known to be positive for the human immunodeficiency virus (HIV).

         11. The patient has an uncontrolled bleeding disorder.

         12. The patient has a family history of congenital or hereditary immunodeficiency.

         13. The patient has psychiatric or addictive disorders that may compromise his/her ability
             to give informed consent or to comply with the trial procedures.

         14. The patient has other concurrent severe medical problems, unrelated to the malignancy,
             that would significantly limit full compliance with the study or expose the patient to
             unacceptable risk.

         15. For female patients: the patient is pregnant or lactating.