Malignant Melanoma With Metastasis
Conditions
Brief summary
The purpose of the study is to assess whether a vaccine containing a small fragment of the protein IDO, which may be present in cancer cells and cells of the immune system, is safe to use in combination with either Ipilimumab or Vemurafenib in the treatment of malignant melanoma that has metastasized.
Interventions
BIOLOGICALVaccine consisting of a peptide derived from the protein IDO
All patients will receive seven vaccines containing IDOlong
Sponsors
Herlev Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria - all patients 1. Age ≥ 18 2. Measurable disease according to RECIST 1.1 3. ECOG performance status ≤ 2 4. Patients with asymptomatic brain metastases allowed (treatment with systemic glucocorticoids is not compatible with participation) 5. Women of childbearing potential must have negative s-hCG prior to initiation of treatment, and use effective contraception during treatment and up to 26 weeks after the last treatment. Safe contraception include: Birth control pills, intrauterine devices, depot injection of progesterone, subdermal implantation (eg Implanon), hormonal vaginal ring and transdermal patch. All patients must meet all inclusion criteria in the treatment group they belong to. Inclusion criteria Vemurafenib and peptide vaccine 1. Histologic confirmed stage III (non-operable) or stage IV melanoma with BRAF V600 documented mutation 2. Patients should be fully recovered from any previous systemic or topical treatment for metastatic malignant melanoma 3. Adequate haematological, renal and hepatic function: * Neutrophils ≥ 1.5 x 10\^9 / l * Platelet count ≥ 100 x 10\^9 / l * Hemoglobin ≥ 5.6 mmol / l * Serum creatinine ≤ 1.5 times upper normal limit * AST or ALT ≤ 2.5 times upper normal limit (≤ 5 times upper normal limit if it is considered that an increase due to liver metastases) * Serum bilirubin ≤ 1.5 times upper normal limit * Alkaline phosphatase ≤ 2.5 times upper normal limit (≤ 5 times upper normal limit if it is considered that an increase due to liver metastases) Inclusion criteria Ipilimumab and peptide vaccine 1. Histologic verified stage III (non-operable) or stage IV malignant melanoma 2. Patients previously treated with anti-CTLA-4 therapy can be included, unless this treatment is stopped due to lack of efficacy or side effects 3. There must be at least 21 days since last systemic treatment of malignant melanoma and the patient must be free of side effects from this treatment. After palliative radiotherapy elsewhere than in the brain, treatment with Ipilimumab and peptide vaccine can be initiated, without a 21 day break. When radiotherapy is used for brain metastases, treatment, however, can only be initiated when the patient is not dependent on prednisolone. 4. Adequate haematological, renal and hepatic function: * Leukocytes ≥ 2 x 10\^9 / l * Neutrophils ≥ 1 x 10\^9 / l * Platelet count ≥ 75 x 10\^9 / l * Hemoglobin ≥ 5.6 mmol / l (possibly after transfusion) * Serum creatinine ≤ 2 times upper limit of normal * AST or ALT ≤ 2.5 times upper normal limit (≤ 5 times upper normal limit if it is considered that an increase due to liver metastases) * Serum bilirubin ≤ 2 times upper normal limit (except for patients with Gilbert's syndrome, which allowed bilirubin up to 3.0 mg / dL)
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events during and after treatment as a Measure of Safety and Tolerability. | Ipilimumab+vaccine combination: Day 84. Vemurafenib+vaccine combination: Day 56. | Primary endpoints will be assessed according to CTCAE ver. 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vaccine related immune response | Ipilimumab: Day 1 (before first treatnent), day 21, day 42, day 63 and at day 84. Thereafter every 12 weeks until progression or up to 104 weeks. Vemurafenib: Day 1, day 28, day 56. Thereafter every 28 days until progression or up to week 104 weeks. | Reactivity towards epitopes nested within the sequence of the peptide used for vaccination, will be assessed in T cells from peripheral blood, obtained at the specified sample times. Reactivity will be assessed using ELISpot technology, where secretion of interferon gamma and tumor necrosis factor alpha is measured during in vitro stimulation with the peptide used for vaccination. In addition to this, combinatorial coding with fluor chrome conjugated HLA tetramers are used to enumerate precursor frequency of CD8 T cells specific for epitopes within the peptide sequence |
Countries
Denmark
Outcome results
None listed