Vaccination With Peptides in Combination With Either Ipilimumab or Vemurafenib for the Treatment of Unresectable Stage III or IV Malignant Melanoma

NCT ID: NCT02077114

Last Updated: 2014-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28

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.

Conditions

Malignant Melanoma With Metastasis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ipilimumab

Patient who according to standard criteria are candidates to treatment with Ipilimumab

Group Type: EXPERIMENTAL

Vaccine consisting of a peptide derived from the protein IDO

Intervention Type: BIOLOGICAL

All patients will receive seven vaccines containing IDOlong

Vemurafenib

Patients who according to standard criteria are candidates to treatment with Vemurafenib

Group Type: EXPERIMENTAL

Vaccine consisting of a peptide derived from the protein IDO

Intervention Type: BIOLOGICAL

All patients will receive seven vaccines containing IDOlong

Interventions

Vaccine consisting of a peptide derived from the protein IDO

All patients will receive seven vaccines containing IDOlong

Intervention Type: BIOLOGICAL

Other Intervention Names

IDOlong

Eligibility Criteria

Inclusion Criteria

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.

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)

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

1. Concomitant immunosuppressive therapy including prednisolone and methotrexate

2. Known infection with HIV, hepatitis B and C virus, even if infection remain stable with medical treatment

3. Other malignancy within the past three years, other than squamous cell and basal cell skin carcinoma

4. Serious somatic disease, severe asthma, severe COPD, poorly controlled cardiovascular disease or diabetes

5. Patients must not have undergone major intestinal surgery within the last 28 days.

6. Severe allergies or previous anaphylactoid reactions

7. Pregnant or lactating women

8. Psychiatric illness that is perceived by the investigator to likely affect patient compliance

9. Known hypersensitivity to ingredients in the adjuvant substances Montanide or Aldara cream

1. At least one of the following within the past six months: myocardial infarction, severe / unstable angina pectoris, symptomatic congestive heart failure, cerebrovascular event or transient ischaemic attack, pulmonary embolism, poorly controlled hypertension,

2. Congenital long QT syndrome, previous or current significant ventricular or atrial dysrhythmia ≥ 2nd degree (NCI CTCAE version 4.0)

3. Corrected QT interval ≥ 450 msec at baseline

4. Uncontrolled medical illness such as infection requiring intravenous antibiotics

5. Other severe acute, chronic or psychiatric condition or abnormal laboratory value, which can increase the risk associated with Vemurafenib treatment

1. Autoimmune diseases: History of inflammatory bowel disease, including Crohn's disease and ulcerative colitis, systemic autoimmune disease eg. rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis, including Wegener granulomatosis. Patients with motor neuropathy believed to be of autoimmune origin such as Guillain-Barre and Myasthenia gravis can not be included in the study.

2. Treatment with any vaccine to prevent infection within 28 prior to initiation of treatment with the peptide vaccine and Ipilimumab

3. Systemic treatment with prednisolone.

4. Life-threatening diseases that require treatment with immunosuppressive agents

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Herlev Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jon Bjørn

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jon Bjørn, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Cancer Immune Therapy

Inge Marie Svane, MD, PhD, Professor

Role: STUDY_CHAIR

Center for Cancer Immune Therapy

Locations

Department of Oncology, Herlev Hospital

Herlev, , Denmark

Countries

Denmark

Related Links

http://www.herlevhospital.dk/ccit-denmark/menu/

Related Info

Other Identifiers

MM1304

Identifier Type: -

Identifier Source: org_study_id