THE IPI - Trial in Advanced Melanoma: Melanoma Patients With Advanced Disease

Inclusion Criteria

Patients meeting all of the following criteria will be considered for admission to the trial:

1. Histologically proven ocular melanoma
2. Measurable disease according to RECIST in unresectable stage III-IV
3. Minimum age of 18 years,
4. Able and willing to give valid written inform consent
5. Patients with or without prior systemic treatment for advanced malignant melanoma are eligible .
6. In case of systemic pre-treatment, an interval of at least 28 days since treatment with chemotherapy, biochemotherapy, surgery, radiation, or immunotherapy is mandatory as well as recovery from any clinically significant toxicity experienced during treatment is recommended. Prior treatment must be completed by the time of ipilimumab administration. Palliative radiation therapy outside of the brain or therapeutic radiation to the brain after the patient's condition is stabilized and systemic steroids required for the management of symptoms due to brain metastases is decreased to the lowest fixed dose possible and does not require the 28-day waiting period. Patient must have recovered from any acute toxicity associated with prior therapy.
7. Expected survival of at least six months
8. ECOG Performance Status 0, 1 or 2.
9. Within the last 2 weeks prior to study day 1 the following laboratory parameters, which should be within the ranges specified:

   Lab Parameter Range White blood cells (WBC) \>= 2500/mm3 (≥ 1 2.5 x 109/L) Absolute neutrophil count (ANC) \>= 1000/mm3 (≥ 1.0 x 109/L) Platelets ≥75.000/mm3 (≥ 75 x 109/L) Hemoglobin ≥ 9 g/dL (≥ 90 g/L; may be transfused) Creatinine \<= 2.0 x ULN Bilirubin total \<= 2.0 x ULN (excepted patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL) \<= 5 x ULN for patients with liver metastases
10. No childbearing potential or negative pregnancy test of women of childbearing potential performed within 7 days prior to the start of treatment.

Women of childbearing potential (WOCP) must be using an effective method of contraception (Pearl-Index \< 1, e.g. oral contraceptives, other hormonal contraceptives \[vaginal products, skin patches, or implanted or injectable products\], or mechanical products such as an intrauterine device or barrier methods \[diaphragm, spermicides\]) throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

No men of fathering potential or men of fathering potential must be using an effective method of contraception to avoid conception throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal.

Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.

WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at Baseline within 7 days before the start of ipilimumab and at week 12.

Exclusion Criteria

Patients will be excluded from the study for any of the following reasons:

1. The patient requires concomitant therapy with any of the following: IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; any other systemic therapy for cancer including any other experimental treatment.
2. The patient requires chronic use of systemic corticosteroids. Systemic steroids for management of symptoms due to brain mets should be avoided if possible or subject should be stable on the lowest clinically effective dose. Topical or inhalational steroids are permitted.
3. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment.
4. Active autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
5. Symptomatic CNS metastases (Remark: Asymptomatic stable, untreated or pretreated central nervous system (CNS) metastasis are allowed)
6. Family history of congenital or hereditary immunodeficiency.
7. The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
8. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
9. Lack of availability for clinical follow-up assessments.
10. The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
11. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
12. Patients with serious intercurrent illness, requiring hospitalization.
13. For female patients: the patient is pregnant or lactating. Women of childbearing potential: Refusal or inability to use effective means of contraception
14. Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
15. Subjects with melanoma who have another active, concurrent, malignant disease are not eligible for this trial, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix.
16. Previous treatment with ipilimumab